Radionuclide drug conjugate, and preparation method therefor and use thereof
Ligase-dependent conjugation using transpeptidases like Sortase enzymes addresses the challenges of efficient and gentle bonding in radionuclide drug conjugation, enhancing scalability and quality control while minimizing antibody damage.
Patent Information
- Application Number
- AU2025240149
- Authority / Receiving Office
- AU · AU
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-08-09
- Filing Date
- 2025-03-21
- Publication Date
- 2026-11-05
AI Technical Summary
Existing methods for conjugating radionuclide drugs with targeting moieties face challenges in achieving efficient and gentle chemical or enzymatic bonding, leading to potential damage to the antibody and difficulties in industrial scalability and quality control.
Employing ligase-dependent conjugation technology, specifically using transpeptidases like Sortase enzymes, to form covalent bonds between targeting moieties and payload units through enzymatic means, optimizing the preparation process for mild reaction conditions and improved product quality.
This approach reduces physical and chemical damage to antibodies during conjugation, facilitates industrial scalability, and enhances the quality control of conjugated products, ensuring efficient and stable bonding.
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Abstract
Description
independently selected from the following 1), 2), and a combination thereof: 1) one or more natural amino acids or oligomeric natural amino acids with a degree of polymerization of 2-20; 2) a chemical bond or C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -S-, -NH-, -(CO)-, C2-6 alkynyl, C3-10 cycloalkylene, 3- to 10-membered heterocycloalkylene, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, alkynyl, cycloalkylene, heterocycloalkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, sulfonyl-C1-10 alkyl, and 3- to 10-membered heterocycloalkyl; each Lb and each Lc, when present, is independently a chemical bond or C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -(CO)-, -NH-, -(C=S)-, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; G is a branching moiety with a branching function, and is directly or indirectly linked to Q and D; wherein each G is independently selected from the following 3), 4), and a combination thereof: 3) one or more natural or non-natural amino acids or oligomeric natural or non-natural amino acids with a degree of polymerization of 2-20; 4) a chemical bond or C1-60 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; j is an integer selected from 1 to 30; k is an integer selected from 1 to 20; o is an integer or non-integer greater than 0 and less than 20. In another aspect, the present disclosure provides a radionuclide conjugate comprising a structure of formula (II) below: wherein formula (II) is a targeting moiety, and the remaining moiety is a payload unit, wherein the targeting moiety and the payload unit form a covalent bond through enzymatic conjugation or chemical conjugation; each Q is independently an albumin-binding unit; preferably, the albumin-binding unit is a small-molecule albumin-binding unit; each D is independently a chelating group for a radionuclide; each La is independently selected from the following 1), 2), and a combination thereof: 1) a natural or non-natural amino acid or an oligomeric natural or non-natural amino acid with a degree of polymerization of 2-20; 2) a chemical bond or C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -S-, -NH-, -(CO)-, C2-6 alkynyl, C3-10 cycloalkylene, 3- to 10-membered heterocycloalkylene, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, alkynyl, cycloalkylene, heterocycloalkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, sulfonyl-C1-10 alkyl, and 3- to 10-membered heterocycloalkyl; each Lb and each Lc, when present, is independently a chemical bond or C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -(CO)-, -NH-, -(C=S)-, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; each G1 or G3, when present, is independently selected from a chemical bond and C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; preferably, each G1 or G3, when present, is independently selected from a chemical bond, optionally substituted -NH-(C1-10 alkylene)-CO-, optionally substituted -NH-PEG-CO-, optionally substituted -NH-PEG-(C1-10 alkylene)-CO-, and optionally substituted -NH-(C1-10 alkylene)-PEG-CO-; the substituent for the substitution is selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl-; PEG is -(CH2CH2O)x- or -(OCH2CH2)y-, and x or y is an integer of 1-20; each G2 or G4, when present, is independently a branching unit; preferably, each G2 or G4 is selected from one of or a combination of more of the following groups: 1) one or more branched natural or non-natural amino acid fragments, wherein preferably, the branched natural or non-natural amino acid fragment has the following structure: -NH-(CR2R3)-CO-, wherein R2 and R3 are each independently selected from hydrogen, optionally substituted -(C1-10 alkylene)-NH-, and optionally substituted -(C1-10 alkylene)-CO-; R2 and R3 are not simultaneously hydrogen; more preferably, the branched natural or non-natural amino acid is a glutamic acid fragment, an aspartic acid fragment, or a lysine fragment; the substituent for the substitution is selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl-; 2) C1-20 linear or branched alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; n1 and n2 are each independently an integer of 0-10; j1, j2, k1, and k2 are each independently an integer of 0-10; o is an integer or non-integer greater than 0 and less than 10. The present disclosure may use ligase-catalyzed conjugation technology (ligase dependent \A conjugation, LDC) to conjugate with the remaining moiety of the compound of formula (I). The ligase here refers to a transpeptidase, including but not limited to various native Sortase enzymes (including Sortase A, Sortase B, Sortase C, Sortase D, Sortase from L. plantarum, and the like; for details, see patents US20110321183A and WO2022160156A), and various preferably engineered novel transpeptidases. The conjugation reaction is achieved by biological enzyme-catalyzed means, with mild reaction conditions, which reduces physical and chemical damage to the antibody during the conjugation. The preparation process and procedure are further optimized, facilitating industrial upgrading, and being conducive to quality control of conjugated products. \A In some embodiments, the targeting moiety and the payload unit form a covalent bond through enzymatic conjugation. In some embodiments, the targeting moiety represents an unmodified or modified targeting moiety. In some embodiments, represents a modified targeting moiety, and the modification is intended to enable to form La of the payload unit \A through reaction with La' under action of a ligase. In some embodiments, contains a ligase recognition substrate, and La' comprises a ligase recognition substrate. In some embodiments, comprises a ligase donor recognition substrate, and La’ comprises a ligase acceptor recognition substrate. In some embodiments, La' comprises a ligase donor recognition substrate, and comprises a ligase acceptor recognition substrate. In some embodiments, comprises a spacer (SP) and a recognition sequence for a ligase donor substrate linked in sequence. In some embodiments, the spacer is selected from GA, GGGGS, GGGGSGGGGS, and GGGGSGGGGSGGGGS; preferably, the spacer is GA. \A In some embodiments, the targeting moiety naturally contains an La moiety that can react with La' to form a payload unit, such as Cys, Lys, and Gln. In some embodiments, the ligase is a Sortase enzyme. In some embodiments, the targeting moiety is modified at its C-terminus or N-terminus and comprises, in sequence, a spacer (SP) and a recognition sequence for a ligase donor substrate. In some embodiments, the spacer is selected from GA, GGGGS, GGGGSGGGGS, and GGGGSGGGGSGGGGS; preferably, the spacer is GA. In some embodiments, the recognition sequence for a ligase donor substrate is LPX1TGX2 (SEQ ID NO: 17), wherein X1 is any natural or non-natural amino acid, and X2 is absent or is an amino acid fragment comprising 1-10 amino acids. In particular, the recognition sequence for a ligase donor substrate is LPETGG (SEQ ID NO: 18). Ligases used in the present disclosure may further include a transglutaminase, a formylglycine-generating enzyme, a tyrosinase, and an asparagine ligase. In some embodiments, a transglutaminase (TGase) catalyzes the reaction between glutamine and lysine and derivatives thereof, and a site-specific conjugation function between the targeting moiety and the payload unit of the present disclosure can be achieved by TGase. TGase cannot recognize naturally-occurring glutamine in a constant region of a glycosylated antibody, and exhibits high specificity. TGase transfers the recognition structure for a transglutaminase acceptor substrate comprised in the payload unit to which comprises the recognition structure for a transglutaminase donor substrate. In some embodiments, the \A targeting moiety comprises an LLQG (SEQ ID NO: 21) peptide fragment, and TGase can specifically recognize glutamine in the LLQG peptide fragment sequence, so that conjugation is performed between the targeting moiety and the payload unit. In some embodiments, under \A the action of the ligase, the targeting moiety of formula (I) forms La of the payload unit \A through reaction with La’, wherein the targeting moiety and La' comprise a recognition structure for a transglutaminase donor substrate or a recognition structure for a transglutaminase acceptor substrate, respectively.In some embodiments, the recognition structure for a transglutaminase donor substrate comprises glutamine. In some embodiments, the targeting \A moiety \A contains glutamine. In some embodiments, the targeting moiety is modified \A by introducing glutamine. In some embodiments, the modified targeting moiety comprises peptide LLQG. In some embodiments, the recognition structure for a transglutaminase acceptor substrate is -NH2. In some embodiments, La' comprises -NH2, e.g., La' comprises -C1-10 alkylene- NH2 or lysine. In some other embodiments, the targeting moiety comprises glutamine. A formylglycine-generating enzyme (FGE) can specifically recognize a CX3PX4R pentapeptide sequence, wherein X3 and X4 are any natural or non-natural amino acids, and replaces a cysteine residue with an aldehyde group. The aldehyde group can further react with a recognition structure for a formylglycine-generating enzyme donor substrate to generate a stable structure. For example, the aldehyde group reacts with dimethylated 2-(hydrazinylmethyl)-3-indole to form a stable carbon-carbon bond through a tetrahydroisoquinoline synthesis (HIPS) reaction at near-neutral pH values. In some embodiments, under action of the ligase, the targeting moiety of formula (I) forms La of the payload unit through reaction with La', wherein the targeting moiety comprises a C-terminus or N-terminus modification, and comprises, in sequence, a spacer (SP) and a recognition sequence for a ligase donor substrate. In some embodiments, the targeting moiety and La' comprise a recognition structure for a formylglycine- generating enzyme donor substrate or a recognition structure for a formylglycine-generating enzyme acceptor substrate, respectively.In some embodiments, the recognition structure for a formylglycine-generating enzyme donor substrate comprises recognition sequence CX3PX4R, wherein X3 and X4 are any natural or non-natural amino acids. In some embodiments, the recognition structure for a formylglycine-generating enzyme acceptor substrate comprises a structure capable of forming a stable reaction product with an aldehyde group. In some embodiments, La' comprises H c or r , wherein the wavy line represents a site of attachment to another structure of the payload unit. In some other embodiments, the targeting \A moiety comprises recognition sequence CX3PX4R, wherein X3 and X4 are any natural or non-natural amino acids. A tyrosinase oxidizes tyrosine to 1,2-quinone, which can undergo a cycloaddition reaction with diverse structures. For example, a cycloaddition reaction takes place with various bicyclo[6.1.0]nonyne (BCN) derivatives. In some embodiments, under the action of the ligase, \A the targeting moiety of formula (I) forms La of the payload unit through reaction with La', wherein the targeting moiety is modified and comprises a recognition sequence for a ligase donor substrate.In some embodiments, the modified targeting moiety and La' comprise a recognition structure for a tyrosinase donor substrate or a recognition structure for a tyrosinase acceptor substrate, respectively.In some embodiments, the recognition structure for a tyrosinase donor substrate comprises tyrosine. In some embodiments, the targeting moiety comprises tyrosine. In some embodiments, the targeting moiety In some embodiments, the modified targeting moiety is modified by introducing tyrosine. comprises tyrosine. In some embodiments, the recognition structure for a tyrosinase acceptor substrate comprises any structure capable of undergoing a cycloaddition reaction with 1,2-quinone to generate a stable product. In some embodiments, La' comprises a bicyclo[6.1.0]nonyne structure. In some other embodiments, the targeting moiety comprises tyrosine. Asparagine ligases of the present disclosure include Singzyme and Butelase. Singzyme specifically recognizes a recognition sequence for a ligase donor substrate NX5L, wherein X5 is any natural or non-natural amino acid, so that ligation is performed with a recognition sequence for a ligase acceptor substrate GI under its mediation. Butelase is an asparagine ligase derived from Clitoria ternatea, which can specifically recognize an Asn-His-Val (NHV) amino acid sequence at the carboxyl-terminus of a polypeptide, and catalyzes a ligation reaction between the Asn residue on the sequence and an arbitrary amino acid residue at the amino-terminus of the same or another polypeptide to form a peptide bond. In some embodiments, under the action of the ligase, the targeting moiety of formula (I) \A forms La of the payload unit through reaction with La’, wherein the targeting moiety and La' comprise a recognition structure for an asparagine ligase donor substrate or a recognition structure for an asparagine ligase acceptor substrate, respectively.In some embodiments, the \A targeting moiety is modified at its C-terminus or N-terminus and comprises, in sequence, a spacer (SP) and a recognition sequence for a ligase donor substrate. In some embodiments, the recognition structure for an asparagine ligase donor substrate comprises recognition sequence NX5L, wherein X5 is any natural or non-natural amino acid, and recognition sequence NHV. In some other embodiments, the recognition structure for an asparagine ligase acceptor substrate comprises amino acid fragment GI. In some embodiments, La' comprises amino acid \A fragment GI. In some other embodiments, the targeting moiety comprises recognition sequences NX5L and NHV, wherein X5 is any natural or non-natural amino acid. The targeting moiety of formula (I) and the payload unit of the present disclosure may also form a covalent bond through chemical conjugation.In some embodiments, the targeting moiety forms La of the payload unit through reaction with La', wherein the targeting moiety comprises lysine and is chemically conjugated to La' via lysine. La' comprises a group capable of reacting with amino, such as carboxyl, carbonyl, allyl, hydroxyl, thiol, and an activated ester. In some embodiments, La' comprises the following structures: 0 , S^=C^=N , and , wherein the wavy line represents a site of attachment to another structure of the payload unit. In some other embodiments, the targeting moiety forms La of the payload unit through reaction with La', wherein the targeting moiety comprises cysteine and is chemically conjugated to La' via cysteine. La' comprises a group capable of reacting with sulfhydryl, such as hydroxyl, carboxyl, and maleimide. In some embodiments, La' comprises the following structures: । and 0 In some embodiments, the targeting moiety is selected from a ligand, a polypeptide, and an antibody or an antigen-binding fragment thereof that specifically bind to a target; preferably, <A the targeting moiety is an antibody or an antigen-binding fragment thereof; more \A preferably, the targeting moiety is selected from a single-domain antibody and a single- \A chain antibody. In one specific embodiment, the targeting moiety specific membrane antigen (PSMA) antibody; preferably, antibody.In one specific embodiment, the targeting moiety is an anti-prostate- is an anti-PSMA single-domain is an anti-epidermal growth factor receptor 2 (HER2) antibody.In another specific embodiment, the targeting moiety is an anti-Delta-like ligand 3 (DLL3) antibody. \A In some embodiments, the targeting moiety comprises an HCDR1 set forth in SEQ ID NO: 1, an HCDR2 set forth in SEQ ID NO: 2, and an HCDR3 set forth in SEQ ID NO: 3. \A In some embodiments, the targeting moiety comprises an HCDR1 set forth in SEQ ID NO: 4, an HCDR2 set forth in SEQ ID NO: 5, and an HCDR3 set forth in SEQ ID NO: 6. \A In some embodiments, the targeting moiety comprises an HCDR1 set forth in SEQ ID NO: 7, an HCDR2 set forth in SEQ ID NO: 8, and an HCDR3 set forth in SEQ ID NO: 9. \A In some embodiments, the targeting moiety comprises an HCDR1 set forth in SEQ ID NO: 23, an HCDR2 set forth in SEQ ID NO: 24, and an HCDR3 set forth in SEQ ID NO: 25. In some embodiments, the targeting moiety comprises the amino acid sequence set forth in SEQ ID NO: 10 or SEQ ID NO: 11, or comprises the amino acid sequence set forth in positions 1 to 127 of SEQ ID NO: 12, or comprises the amino acid sequence set forth in positions 1 to 115 of SEQ ID NO: 22.In some other embodiments, the targeting moiety comprises an amino acid sequence having at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the amino acid sequence set forth in SEQ ID NO: 10 or SEQ ID NO: 11.In still other embodiments, the targeting moiety \ comprises an amino acid sequence having at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the amino acid sequence set forth in positions 1 to 127 of SEQ ID NO: 12.In some other embodiments, the targeting moiety comprises an amino acid sequence having at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the amino acid sequence set forth in positions 1 to 115 of SEQ ID NO: 22. \A In some embodiments, the targeting moiety comprises the amino acid sequence set forth \A in SEQ ID NO: 10.In some embodiments, the targeting moiety comprises the amino acid <A sequence set forth in SEQ ID NO: 1EIn some embodiments, the targeting moiety comprises the amino acid sequence set forth in positions 1 to 127 of SEQ ID NO: 12.In some \A other embodiments, the targeting moiety positions 1 to 115 of SEQ ID NO: 22. comprises the amino acid sequence set forth in \A In some embodiments, the modified targeting moiety comprises the amino acid sequence \A set forth in SEQ ID NO: 12.In some embodiments, when the targeting moiety is linked to Gly in formula (I), its C-terminal amino acid sequence GGHHHHHH (SEQ ID NO: 19) is cleaved by a Sortase enzyme.In some embodiments, the modified targeting moiety comprises the amino acid sequence set forth in positions 1 to 133 of SEQ ID NO: 12. \A In some embodiments, the modified targeting moiety comprises the amino acid sequence \A set forth in SEQ ID NO: 13.In some embodiments, when the targeting moiety is linked to Gly in formula (I) or (II), its C-terminal amino acid sequence GG is cleaved by a Sortase enzyme.In some embodiments, the modified targeting moiety sequence set forth in positions 1 to 141 of SEQ ID NO: 13. <A comprises the amino acid In some embodiments, the modified targeting moiety comprises the amino acid sequence set forth in SEQ ID NO: 22.In some embodiments, when the targeting moiety is linked to Gly in formula (I) or (II), its C-terminal amino acid sequence GGHHHHHH (SEQ ID NO: 19) is cleaved by a Sortase enzyme.In some embodiments, the modified targeting moiety comprises the amino acid sequence set forth in positions 1 to 121 of SEQ ID NO: 22. In some embodiments, each La is independently selected from the following structures: -(Gly)n-, wherein n is an integer selected from 2 to 20, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20; preferably, n is an integer of 2-10, more preferably 3; -NH-C1-10 alkylene-(CO)-, preferably -NH-(CH2)4-(CO)-; C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -(CO)-, C2-6 alkynyl, C6-10 arylene, and 6- to 10-membered heteroarylene; preferably, each La is independently ' wavy line marked with * represents a site of attachment to the targeting moiety wavy line represents a site of attachment to G of the payload unit; and , wherein the <A , and the C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -(CO)- and 3- to 10-membered heterocycloalkylene; preferably, each La is independently represents a site of attachment to the targeting moiety of attachment to G of the payload unit. , wherein the wavy line marked with * <A , and the wavy line represents a site In some specific embodiments, each La is independently selected from the following structures: -(Gly)3-, -NH-(CH2)4-(CO)-, , and wherein the wavy line marked with * represents a site of attachment to the targeting moiety \, and the wavy line represents a site of attachment to G of the payload unit. In some embodiments, each G is independently selected from a combination of 3) and 4) below: 3) one or more natural or non-natural amino acids or oligomeric natural or non-natural amino acids with a degree of polymerization of 2-20; 4) a chemical bond or C1-60 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, sulfonyl-C1-10 alkyl, and 3- to 10-membered heterocycloalkyl. In some specific embodiments, each G is independently selected from the following structures: , 10 N N wherein g is an integer selected from 1 to 20, preferably an integer of 1-5; preferably, 5 9 , and wherein g is an integer selected from 1 to 20, preferably an integer of 1-5; 5 more preferably, and HN 5 , further preferably, wherein the wavy line marked with * represents a site of attachment to La, the wavy line marked with # represents a site of attachment to Lc or Lb, and the wavy line represents a site of attachment to Lb or Lc. In some embodiments, G1 and G3 are each independently selected from a chemical bond and the following structures: 0' o an In some preferred embodiments, G2 and G4 are fragment or a combination thereof: . each independently the following structural HN" OH H , , wherein one terminus of the wavy line marked with * is a terminus proximal to In some more preferred embodiments, G2 and G4 are each independently the following structural fragment or a combination thereof: HN^ o or H H , wherein one terminus of the wavy line marked with * is a terminus proximal to In some embodiments, PEG is -(CH2CH2O)x- or -(OCH2CH2)y-, wherein x or y is an integer of 1-10, preferably an integer of 2-6, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some embodiments, each Lb is independently selected from a chemical bond and C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -(CO)-, -NH-, -(C=S)-, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl. In some specific embodiments, each Lb is independently selected from a chemical bond, H , and N N H H , wherein the wavy line marked with * represents a site of attachment to D, and the wavy line represents a site of attachment to G, G2, or G4. In some embodiments, Lc is a chemical bond. In some other embodiments, Lc is * H G. Ax h , wherein the wavy line marked with * represents a site of attachment to Q, and the wavy line represents a site of attachment to G, G2, or G4. In some embodiments, Q is a small-molecule binder. In some other embodiments, each Q is , , , , and independently selected from the following structures: , wherein R1 is selected from H, C1-6 alkyl, halogen, methoxy, and trifluoromethyl; preferably, R1 is selected from methyl and iodine; Ra1 to Ra11 are each independently selected from hydrogen, C1-6 alkyl, C1-6 alkoxy, halogen, cyano, nitro, amino, and hydroxyl. In some specific embodiments, each Q is independently selected from o , and In some embodiments, D is a chelating group for a radionuclide. In some other embodiments, each D is independently selected from: bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (CBTE2a), cyclohexyl-1,2-diaminetetraacetic acid (CDTA), 4-(1,4,8,11-tetraazacyclotetradec-1-yl)-methylbenzoic acid (CPTA), N'-[5-[acetyl(hydroxy)amino]pentyl]-N-[5-[[4-[5-aminopentyl-(hydroxy)amino]-4-oxobutanoyl]amino]pentyl]-N-hydroxybutanediamide (DFO), 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (DO2A), 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA), a-(2-carboxyethyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTAGA), 1,4,7,10-azacyclododecane-N,N',N'',N'''-1,4,7,10-tetra(methylene)phosphonic acid (DOTMP), N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5''-bis(phosphate) (DPDP), diethylenetriamine-N,N',N''-penta(methylene)phosphonic acid (DTMP), diethylenetriaminepentaacetic acid (DTPA), ethylenediamine-N,N'-tetraacetic acid (EDTA), ethylene glycol-O,O-bis(2-aminoethyl)-N,N,N'',N''-tetraacetic acid (EGTA), N,N-bis(hydroxybenzyl)- ethylenediamine-N,N''-diacetic acid (HBED), hydroxyethylethylenediaminetriacetic acid (HEDTA), 1-(p-nitrobenzyl)-1,4,7,10-tetraazacyclodecane-4,7,10-triacetate (HP-DOA3), 6-hydrazinyl-N- methylpyridine-3-carboxamide (HYNIC), tetra 3-hydroxy-N-methyl-2-pyridone chelator abbreviated as Me-3,2-HOPO (4-((4-(3-(bis(2-(3-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamido)ethyl)amino)-2-((bis(2-(3-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamido)ethyl)amino)methyl)propyl)phenyl)amino)-4-oxobutanoic acid), 1,4,7-triazacyclononane-1-succinic acid-4,7-diacetic acid (NODASA), 1-(1-carboxy-3-carboxypropyl)-4,7-(carboxy)-1,4,7-triazacyclononane (NODAGA), 1,4,7-triazacyclononanetriacetic acid (NOTA), 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (TE2A), 1,4,8,11-tetraazacyclododecane-1,4,8,11-tetraacetic acid (TETA), tris(hydroxypyridone) (THP), terpyridine-bis(methyleneaminetetraacetic acid) (TMT), 1,4,7-triazacyclononane-1,4,7-tris[methylene(2-carboxyethyl)phosphinic acid] (TRAP), 1,4,7,10-tetraazacyclotridecane-N,N',N'',N'''-tetraacetic acid (TRITA), 3-[[4,7-bis[[2-carboxyethyl(hydroxy)phosphoryl]methyl]-1,4,7-triazacyclononan-1- yl]methyl-hydroxy-phosphoryl]propanoic acid, triethylenetetraminehexaacetic acid (TTHA), and N1-(5-aminopentyl)-N1-hydroxy-N4-(5-(N-hydroxy-4-((5-(N-hydroxyacetamido)pentyl)amino)-4-oxobutanamido)pentyl)butanediamide. In some specific embodiments, each D is independently selected from 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, 1,4,7-triazacyclononanetriacetic acid (NOTA), and N1-(5-aminopentyl)-N1-hydroxy-N4-(5-(N-hydroxy-4-((5-(N-hydroxyacetamido)pentyl)amino)-4-oxobutanamido)pentyl)butanediamide. In some embodiments, the radionuclide is selected from any radioactive cation or anion of F, Br, I, Sc, Cu, Ga, Y, In, Lu, Tc, Sm, Sr, Ra, Tb, Ho, Re, Pb, Bi, Ac, Th, Co, Gd, Dy, Zr, At, and Er. Preferably, the radionuclide is selected from 18F, 77Br, 131I, 125I, 43Sc, 44Sc, 47Sc, 64Cu, 67Cu, 67Ga, 68Ga, 86Y, 90Y, 90In, 111In, 177Lu, 94Tc, 99Tc, 153Sm, 89Sr, 223Ra, 151Tb, 166Ho, 186Re, 188Re, 212Pb, 213Bi, 212Bi, 225Ac, 227Th, 55Co, 57Co, 152Gd, 153Gd, 157Gd, 166Dy, 89Zr, and 211At, more preferably 68Ga, 64Cu, and 177Lu. In some embodiments, j is an integer selected from 1 to 10, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some other embodiments, k is an integer selected from 1 to 10, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In still other embodiments, o is an integer or non-integer greater than 0 and less than 10. In some embodiments, formula (I) is selected from the following structures: H H N. A O' '0' '0' ,HN 0 co2h LPET GA N Y 11 N N 'N Y 11 N N HOOC-^ / ^COOH • 5 preferably, uxk — coon , and more preferably, HOOC^ \— / ^COOH , and wherein -S- and -GA-LPET- in the structure described above are portions of the amino acids \A comprised in the targeting moiety In one specific embodiment, j is 1, k is 1, o is 1, La is -(Gly)3-, Lb is , Lc is a -GA' A , Lc is a O 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is H N chemical bond, G is In one specific embodiment, the compound of formula (I) has the following structure: In one specific embodiment, j is 1, k is 1, o is 1, La is -(Gly)3-, Lb is D is In one specific embodiment, the compound of formula (I) has the following structure: Cl CO2H In one specific embodiment, j is 1, k is 1, o is 1, La is -(Gly)3-, Lb is , Lc is a O' chemical bond, G is H , D is 0 5 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is In one specific embodiment, the compound of formula (I) has the following structure: ho2c o COnH H N , D is In one specific embodiment, j is 1, k is 1, o is 1, La is -(Gly)3-, Lb is , Lc is a chemical bond, G is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is O 5 ^. In one specific embodiment, the compound of formula (I) has the following structure: In one specific embodiment, j is 1, k is 1, o is 1, La is -(Gly)3-, Lb is . ,LPET\ GA (or ). h , Lc is a chemical bond, G is O 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is D is 5 In one specific embodiment, the compound of formula (I) has the following structure: COoH ---N , Lc is a H N chemical bond, G is , D is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is In one specific embodiment, j is 1, k is 1, o is 1, La is -(Gly)3-, Lb is In one specific embodiment, the compound of formula (I) has the following structure: COOH ^^^cooh (or GA, LPET COOH N. N M H / N In one specific embodiment, j is 1, k is 1, o is 1, La is HOOC^^^COOH ). -(Gly)3-, Lb is a chemical bond, Lc is a # HN% '0' H 2 f y'^-A0" I k H o 5 chemical bond, G is HN>£ TA ’ , D is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is In one specific embodiment, the compound of formula (I) has the following structure: (or ). In one specific embodiment, j is 1, k is 2, o is 1, La is -(Gly)3-, Lb is , Lc is a chemical bond, G is , D is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is In one specific embodiment, the compound of formula (I) has the following structure: HOOC^^^COOH (or HOOC^^^COOH ). In one specific embodiment, j is 1, k is 1, o is 1, La is -(Gly)3-, Lb is 10 , Lc is a chemical bond, G is HN H N , D is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is 0 . In another embodiment, j is 1, k is 1, o is 1, La is -(Gly)3-, Lb is a chemical bond, Lc is a chemical bond, G is D is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is In one specific embodiment, the compound of formula (I) has the following structure: H n H H In one specific embodiment, j is 1, k is 1, o is 1, La is -(Gly)3-, Lb is H S S H H \= / H , Lc is a chemical bond, G is D is N1-(5-aminopentyl)-N1- hydroxy-N4-(5-(N-hydroxy-4-((5-(N-hydroxyacetamido)pentyl)amino)-4- oxobutanamido)pentyl)butanediamide, and Q is 10 In one specific embodiment, the compound of formula (I) has the following structure: (or In one specific embodiment, j is 1, k is 1, o is 1, La is -(Gly)3-, Lb is ). , Lc is a chemical bond, G is acid (NOTA), and Q is , D is 1,4,7-triazacyclononanetriacetic In one specific embodiment, the compound of formula (I) has the following structure: (or ,LPET\ GA ). In one specific embodiment, j is 1, k is 1, o is 1, La is -NH-(CH2)4-(CO)-, Lb is * H u 10 H N h , Lc is a chemical bond, G is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is In one specific embodiment, the compound of formula (I) has the following structure: (or ho2c—co2h , wherein Q represents glutamine comprised in the targeting moiety In one specific embodiment, j is 1, k is 1, o is 1, La is * , Lc is a chemical bond, G is D is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is In one specific embodiment, the compound of formula (I) has the following structure: wherein s represents a sulfur atom of the cysteine comprised in the targeting moiety ho2c^^^co2h ) In one specific embodiment, j is 1, k is 1, o is 1, La is , Lb is , Lc is a chemical bond, G is D is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is 10 In one specific embodiment, the compound of formula (I) has the following structure: \A wherein s represents a sulfur atom of the cysteine comprised in the targeting moiety (or HO2C^^^CO2H ) In one specific embodiment, j is 1, k is 1, o is 1, La is -(Gly)3-, Lb is a chemical bond, Lc is a chemical bond, G is O , D is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is In one specific embodiment, the compound of formula (I) has the following structure: N y • h , Lc is a H tvN In one specific embodiment, j is 1, k is 1, o is 1, La is -(Gly)3-, Lb is 10 chemical bond, G is HN H N , D is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is In one specific embodiment, the compound of formula (I) has the following structure: HOOC , Lc is a H N chemical bond, G is COOH . 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is In one specific embodiment, j is 1, k is 1, o is 1, La is -(Gly)3-, Lb is , D is In one specific embodiment, the compound of formula (I) has the following structure: HOOC^ COOII . 10 The present disclosure also relates to a conjugate comprising a structure of formula (I'): wherein formula (I') 15 Q is an albumin-binding unit; D and D' are each independently a chelating group for a radionuclide; A is a targeting moiety comprising an antibody or an antigen-binding fragment thereof; preferably, the antibody is selected from a single-domain antibody and a single-chain antibody; Ld is selected from a chemical bond and C1-60 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-; L1, L2, L1', and L2' are each independently a chemical bond or an amino acid fragment with a degree of polymerization of 1-10, or selected from one or a combination of the following divalent groups: C1-10 alkylene, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, nitro, cyano, and C1-10 alkyl; m is an integer selected from 0 to 20; n is an integer selected from 2 to 20; z is an integer selected from 1 to 20. The present disclosure may use ligase-catalyzed conjugation technology (ligase dependent conjugation, LDC) to conjugate A to the remaining moiety of the compound of formula (I). The ligase here refers to a transpeptidase, including but not limited to various native Sortase enzymes (including Sortase A, Sortase B, Sortase C, Sortase D, Sortase from L. plantarum, and the like; for details, see patents US20110321183A and WO2022160156A), and various preferably engineered novel transpeptidases. The conjugation reaction is achieved by biological enzyme-catalyzed means, with mild reaction conditions, which reduces physical and chemical damage to the antibody during the conjugation. The preparation process and procedure are further optimized, facilitating industrial upgrading, and being conducive to quality control of conjugated products. In some embodiments, a terminus of A is modified to be conjugated with a (Gly)n moiety in formula (I) under action of a ligase. In some embodiments, the ligase is a Sortase enzyme. In some embodiments, A comprises an antibody with a C-terminal modification or an N-terminal modification. In some embodiments, an antibody, a spacer (SP), and a recognition sequence for a ligase donor substrate are linked in sequence. In some embodiments, an antibody and a recognition sequence for a ligase donor substrate are linked in sequence. In some embodiments, the spacer is selected from GA, GGGGS, GGGGSGGGGS, and GGGGSGGGGSGGGGS; preferably, the spacer is GA. In some embodiments, the recognition sequence for a ligase donor substrate is LPX1TGX2 (SEQ ID NO: 17), wherein X1 is any natural or non-natural amino acid, and X2 is absent or is an amino acid fragment comprising 1-10 amino acids. In particular, the recognition sequence for a ligase donor substrate is LPETGG (SEQ ID NO: 18). In some embodiments, antibody A is an anti-prostate-specific membrane antigen (PSMA) antibody; preferably, antibody A is an anti-PSMA single-domain antibody. In some other embodiments, antibody A is an anti-epidermal growth factor receptor 2 (HER2) antibody. In still other embodiments, antibody A is an anti-Delta-like ligand 3 (DLL3) antibody. In some embodiments, antibody A comprises an HCDR1 set forth in SEQ ID NO: 1, an HCDR2 set forth in SEQ ID NO: 2, and an HCDR3 set forth in SEQ ID NO: 3. In some embodiments, antibody A comprises an HCDR1 set forth in SEQ ID NO: 4, an HCDR2 set forth in SEQ ID NO: 5, and an HCDR3 set forth in SEQ ID NO: 6. In some embodiments, antibody A comprises an HCDR1 set forth in SEQ ID NO: 7, an HCDR2 set forth in SEQ ID NO: 8, and an HCDR3 set forth in SEQ ID NO: 9. In some embodiments, antibody A comprises an HCDR1 set forth in SEQ ID NO: 23, an HCDR2 set forth in SEQ ID NO: 24, and an HCDR3 set forth in SEQ ID NO: 25. In some embodiments, antibody A comprises the amino acid sequence set forth in SEQ ID NO: 10 or SEQ ID NO: 11, or comprises the amino acid sequence set forth in positions 1 to 127 of SEQ ID NO: 12, or comprises the amino acid sequence set forth in positions 1 to 115 of SEQ ID NO: 22. In some embodiments, antibody A comprises an amino acid sequence having at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the amino acid sequence set forth in SEQ ID NO: 10 or SEQ ID NO: 11. In some embodiments, antibody A comprises an amino acid sequence having at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the amino acid sequence set forth in positions 1 to 127 of SEQ ID NO: 12. In some embodiments, antibody A comprises an amino acid sequence having at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the amino acid sequence set forth in positions 1 to 115 of SEQ ID NO: 22. In some embodiments, antibody A comprises the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, antibody A comprises the amino acid sequence set forth in SEQ ID NO: 11. In some embodiments, antibody A comprises the amino acid sequence set forth in positions 1 to 127 of SEQ ID NO: 12. In some embodiments, antibody A comprises the amino acid sequence set forth in positions 1 to 115 of SEQ ID NO: 22. In some embodiments, modified antibody A comprises the amino acid sequence set forth in SEQ ID NO: 12. In some embodiments, when antibody A is linked to Gly in formula (I'), its C-terminal amino acid sequence GGHHHHHH (SEQ ID NO: 19) is cleaved by a Sortase enzyme. In some embodiments, modified antibody A comprises the amino acid sequence set forth in positions 1 to 133 of SEQ ID NO: 12. In some embodiments, modified antibody A comprises the amino acid sequence set forth in SEQ ID NO: 13. In some embodiments, when antibody A is linked to Gly in formula (I'), its C-terminal amino acid sequence GG is cleaved by a Sortase enzyme. In some embodiments, modified antibody A comprises the amino acid sequence set forth in positions 1 to 141 of SEQ ID NO: 13. In some embodiments, modified antibody A comprises the amino acid sequence set forth in SEQ ID NO: 22. In some embodiments, when antibody A is linked to Gly in formula (I'), its C-terminal amino acid sequence GGHHHHHH (SEQ ID NO: 19) is cleaved by a Sortase enzyme. In some embodiments, modified antibody A comprises the amino acid sequence set forth in positions 1 to 121 of SEQ ID NO: 22. In some embodiments, Ld is selected from a chemical bond, -NH-C1-20 alkylene-(CO)-, and -NH-(PEG)i-(CO)-, wherein (PEG)i comprises 1-20 structural units selected from -(O-C2H4)-and -(C2H4-O)-, and is optionally linked to C1-10 alkylene at at least one terminus of the -(O-C2H4)- or -(C2H4-O)- structural unit. In some embodiments, i is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20. In some embodiments, Ld is -NH-(PEG)i-(CO)-, wherein (PEG)i is 1-20 consecutive -(O-C2H4)- or -(C2H4-O)- structural units, and is optionally linked to C1-10 alkylene at at least one terminus of the -(O-C2H4)- or -(C2H4-O)- structural unit; preferably, Ld is -NH-(PEG)i-C1-10 alkylene-(CO)-; more preferably, Ld is -NH-PEG4-C2H4-(CO)-, -NH-PEG3-C2H4-(CO)-, or -NH-PEG4-C3H6-(CO)-; further preferably, Ld is -NH-(C2H4-O)4-C2H4-(CO)-. In some embodiments, Ld is -NH-(PEG)i-C1-10 alkylene-(CO)-, wherein i is an integer selected from 1 to 12; preferably, i is 2, 3, 4, 5, or 6; more preferably, i is 4. In some embodiments, Ld is -NH-(PEG)i-(CO)-, wherein i is an integer selected from 1 to 12; preferably, i is 2, 3, 4, 5, or 6; more preferably, i is 4. In some embodiments, Ld is -NH-PEG4-(CO)-. In some embodiments, L1 and L1' are each independently selected from any one of a chemical bond, C1-10 alkylene, -NH-, and -(CO)-, or any combination thereof; preferably, L1 is selected from -(CH2)4-NH-, -CO-NH-C2H4-NH-, and -NH-, and L1' is selected from a chemical bond, -(CH2)4-NH-, -CO-NH-C2H4-NH-, and -NH-. In some embodiments, L1 and L1' are identical. In some embodiments, L2 and L2' are each independently selected from any one of a chemical bond, an amino acid fragment with a degree of polymerization of 1-10, -(CO)-, C1-10 alkylene, and -NH-, or any combination thereof; preferably, L2 is selected from -(CO)-, -(CH2)4-NH-, -CO-amino acid fragment with degree of polymerization of 1-10-, and -CO-Lys-, and L2' is selected from a chemical bond, -(CO)-, -(CH2)4-NH-, -CO-amino acid fragment with degree of polymerization of 1-10-, and -CO-Lys-. In some embodiments, L2 and L2' are identical. In some embodiments, m is an integer selected from 0 to 10; preferably, m is 0, 1, or 2; more preferably, m is 0 or 1. In some embodiments, n is an integer selected from 2 to 10; preferably, n is 2, 3, or 4; more preferably, n is 3. In some embodiments, z is an integer selected from 1 to 10; preferably, z is 1, 2, 3, or 4; more preferably, z is 1. In some embodiments, D and D' are each independently selected from bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (CBTE2a), cyclohexyl-1,2-diaminetetraacetic acid (CDTA), 4-(1,4,8,11-tetraazacyclotetradec-1-yl)-methylbenzoic acid (CPTA), N'-[5-[acetyl(hydroxy)amino]pentyl]-N-[5-[[4-[5-aminopentyl-(hydroxy)amino]-4-oxobutanoyl]a mino]pentyl]-N-hydroxybutanediamide (DFO), 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (DO2A), 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA), a-(2-carboxyethyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTAGA), 1,4,7,10-azacyclododecane-N,N',N'',N'''-1,4,7,10-tetra(methylene)phosphonic acid (DOTMP), N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5''-bis(phosphate) (DPDP), diethylenetriamine-N,N',N''-penta(methylene)phosphonic acid (DTMP), diethylenetriaminepentaacetic acid (DTPA), ethylenediamine-N,N'-tetraacetic acid (EDTA), ethylene glycol-O,O-bis(2-aminoethyl)-N,N,N'',N''-tetraacetic acid (EGTA), N,N-bis(hydroxybenzyl)-ethylenediamine-N,N''-diacetic acid (HBED), hydroxyethylethylenediaminetriacetic acid (HEDTA), 1-(p-nitrobenzyl)-1,4,7,10-tetraazacyclodecane-4,7,10-triacetate (HP-DOA3), 6-hydrazinyl-N-methylpyridine-3-carboxamide (HYNIC), tetra 3-hydroxy-N-methyl-2-pyridone chelator abbreviated as Me-3,2-HOPO (4-((4-(3-(bis(2-(3-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamido)ethyl)amino)-2-((bis(2-(3-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamido)ethyl)amino)methyl)prop yl)phenyl)amino)-4-oxobutanoic acid), 1,4,7-triazacyclononane-1-succinic acid-4,7-diacetic acid (NODASA), 1-(1-carboxy-3-carboxypropyl)-4,7-(carboxy)-1,4,7-triazacyclononane (NODAGA), 1,4,7-triazacyclononanetriacetic acid (NOTA), 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (TE2A), 1,4,8,11-tetraazacyclododecane-1,4,8,11-tetraacetic acid (TETA), tris(hydroxypyridone) (THP), terpyridine-bis(methyleneaminetetraacetic acid) (TMT), 1,4,7-triazacyclononane-1,4,7-tris[methylene(2-carboxyethyl)phosphinic acid] (TRAP), 1,4,7,10-tetraazacyclotridecane-N,N',N'',N'''-tetraacetic acid (TRITA), 3-[[4,7-bis[[2-carboxyethyl(hydroxy)phosphoryl]methyl]-1,4,7-triazacyclononan-1-yl]methyl-hyd roxy-phosphoryl]propanoic acid, and triethylenetetraminehexaacetic acid (TTHA); preferably, D is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid; D' is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid. In some embodiments, the radionuclide is selected from any radioactive cation or anion of F, Br, I, Sc, Cu, Ga, Y, In, Lu, Tc, Sm, Sr, Ra, Tb, Ho, Re, Pb, Bi, Ac, Th, Co, Gd, Dy, Zr, At, and Er. Preferably, the radionuclide is selected from 18F, 77Br, 131I, 125I, 43Sc, 44Sc, 47Sc, 64Cu, 67Cu, 67Ga, 68Ga, 86Y, 90Y, 90In, 111In, 177Lu, 94Tc, 99Tc, 153Sm, 89Sr, 223Ra, 151Tb, 166Ho, 186Re, 188Re, 212Pb, 213Bi, 212Bi, 225Ac, 227Th, 55Co, 57Co, 152Gd, 153Gd, 157Gd, 166Dy, 89Zr, and 211At, preferably 68Ga, 64Cu, and 177Lu. In some embodiments, Q is selected from represents a site attached to L2 in formula (I'), wherein R1 is selected from H, C1-6 alkyl, halogen, methoxy, and trifluoromethyl; preferably, halogen is 5 fluorine, chlorine, bromine, or iodine; preferably, R1 is selected from methyl and iodine; Ra1 to Ra11 are each independently selected from hydrogen, C1-6 alkyl, C1-6 alkoxy, halogen, cyano, nitro, amino, and hydroxyl; preferably, halogen is fluorine, chlorine, bromine, or iodine; In some embodiments, m is 0, and the conjugate of formula (I') has a structure represented by formula (I''): D z formula (I''), 10 wherein the groups are as defined for formula (I') of the present disclosure. In one specific embodiment, m is 0, n is 3, z is 1, Ld is -NH-(C2H4-O)4-C2H4-(CO)-, L1 is -(CH2)4-NH-, L2 is -(CO)-, D is 1,4,7,10-tetraazacyclododecane- N,N,N",N"'-tetraacetic acid, h2n so3h HO so3h and Q is / \ . In one specific embodiment, the 15 compound of formula (I') has the following structure: In one specific embodiment, m is 1, n is 3, z is 1, Ld is -NH-(C2H4-O)4-C2H4-(CO)-, L1 and L1' are -(CH2)4-NH-, L2 and L2' are -(CO)-, D and D' are 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is formula (I') has the following structure: In one specific embodiment, m is 0, n is 3, z is 1, Ld is -NH-(C2H4-O)4-C2H4-(CO)-, L1 is -CO- NH-C2H4-NH-, L2 is -(CH2)4-NH-, D is 1,4,7,10-tetraazacyclododecane- N,N',N'',N'''-tetraacetic acid, and Q is one specific embodiment, the compound of formula (I') has the following structure: HOOC—' 1 COOH . In one specific embodiment, m is 0, n is 3, z is 1, Ld is -NH-(C2H4-O)4-C2H4-(CO)-, L1 is -CO- NH-C2H4-NH-, L2 is -(CH2)4-NH-, D is 1,4,7,10-tetraazacyclododecane- N, N, N', N"’-tetraacetic acid, and Q is . 10 In one specific embodiment, the compound of formula (I') has the following structure: 1100( ^ --- / ' (OOI I . Another aspect of the present disclosure provides a compound comprising a structure of formula (III) below: 15 j k formula (III) wherein each Q is independently an albumin-binding unit; each D is independently a chelating group for a radionuclide; La' is selected from the following 1), 2), and a combination thereof: 1) one or more natural or non-natural amino acids or oligomeric natural or non-natural amino acids with a degree of polymerization of 2-20; 2) C1-20 alkyl, wherein a carbon chain unit of the alkyl is optionally replaced with at least one substituent selected from -O-, -S-, -NH-, -(CO)-, C2-6 alkynyl, C3-10 cycloalkylene, 3- to 10membered heterocycloalkylene, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, alkynyl, cycloalkylene, heterocycloalkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, sulfonyl-C1-10 alkyl, and 3- to 10-membered heterocycloalkyl; each Lb and each Lc, when present, is independently a chemical bond or C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -(CO)-, -NH-, -(C=S)-, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; G is a branching moiety with a branching function, and is directly or indirectly linked to Q and D, wherein each G is independently selected from the following 3), 4), and a combination thereof: 3) one or more natural or non-natural amino acids or oligomeric natural or non-natural amino acids with a degree of polymerization of 2-20; 4) a chemical bond or C1-60 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; j is an integer selected from 1 to 30; k is an integer selected from 1 to 20. In yet another aspect, the present disclosure further provides a compound comprising a structure formula (IV) wherein each Q is independently an albumin-binding unit; preferably, the albumin-binding unit is a small-molecule albumin-binding unit; each D is independently a chelating group for a radionuclide; each La' is independently selected from the following 1), 2), and a combination thereof: 1) a natural or non-natural amino acid or an oligomeric natural or non-natural amino acid with a degree of polymerization of 2-20; 2) C1-20 alkyl, wherein a carbon chain unit of the alkyl is optionally replaced with at least one substituent selected from -O-, -S-, -NH-, -(CO)-, C2-6 alkynyl, C3-10 cycloalkylene, 3- to 10membered heterocycloalkylene, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, alkynyl, cycloalkylene, heterocycloalkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, sulfonyl-C1-10 alkyl, and 3- to 10-membered heterocycloalkyl; each Lb and each Lc, when present, is independently a chemical bond or C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -(CO)-, -NH-, -(C=S)-, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; each G1 or G3, when present, is independently selected from a chemical bond and C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; preferably, each G1 or G3, when present, is independently selected from a chemical bond, optionally substituted -NH-(C1-10 alkylene)-CO-, optionally substituted -NH-PEG-CO-, optionally substituted -NH-PEG-(C1-10 alkylene)-CO-, and optionally substituted -NH-(C1-10 alkylene)-PEG-CO-; the substituent for the substitution is selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl-; PEG is -(CH2CH2O)x- or -(OCH2CH2)y-, and x or y is an integer of 1-20; each G2 or G4, when present, is independently a branching unit; preferably, each G2 or G4 is selected from one of or a combination of more of the following groups: 1) one or more branched natural or non-natural amino acid fragments, wherein preferably, the branched natural or non-natural amino acid fragment has the following structure: -NH-(CR2R3)-CO-, wherein R2 and R3 are each independently selected from hydrogen, optionally substituted -(C1-10 alkylene)-NH-, and optionally substituted -(C1-10 alkylene)-CO-; R2 and R3 are not simultaneously hydrogen; more preferably, the branched natural or non-natural amino acid is a glutamic acid fragment, an aspartic acid fragment, or a lysine fragment; the substituent for the substitution is selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl-; 2) C1-20 linear or branched alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; n1 and n2 are each independently an integer of 0-10; j1, j2, k1, and k2 are each independently an integer of 0-10. In some embodiments, La' is selected from the following structures: (Gly)n-, wherein n is an integer selected from 2 to 20, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20, preferably, n is an integer of 2-10, more preferably 3; C1-10 alkyl-(CO)-, wherein the alkyl is substituted with a substituent of amino; preferably NH2-(CH2)4-(CO)-; C1-10 alkyl, wherein a carbon chain unit of the alkyl is optionally replaced with a substituent selected from -(CO)-, C2-6 alkynyl, and / or 5- to 10-membered heteroarylene, wherein the heteroarylene is substituted with a substituent of sulfonyl-C1-10 alkyl; preferably 0 , wherein the wavy line represents a site of attachment to G or G1; C1-10 alkyl, wherein a carbon chain unit of the alkyl is optionally replaced with a substituent of -(CO)-, and the alkyl is substituted with 3- to 10-membered heterocycloalkyl; preferably 0 , wherein the wavy line represents a site of attachment to G or G1; and C1-10 alkyl, wherein a carbon chain unit of the alkyl is optionally replaced with at least one substituent selected from -(CO)-, and the alkyl is substituted with at least one amino; preferably o , wherein the wavy line represents a site of attachment to G or G1. In some specific embodiments, La' is selected from the following structures: (Gly)3-, NH2-(CH2)4-(CO)-, , and wherein the wavy line represents a site of attachment to G or G1. In some embodiments, G is selected from a combination of 3) and 4) below: 3) one or more natural or non-natural amino acids or oligomeric natural or non-natural amino acids with a degree of polymerization of 2-20; 4) a chemical bond or C1-60 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl. In some specific embodiments, G is selected from the following structures: 10 # HN% 9 , and wherein g is an integer selected from 1 to 20, preferably an integer of 1-5; preferably, # HN% 9 , and wherein g is an integer selected from 1 to 20, preferably an integer of 1-5; more preferably, further preferably, # HN% # # HN^- HN^ # , and wherein the wavy line marked with * represents a site of attachment to La', the wavy line marked with # represents a site of attachment to Lc, and the wavy line represents a site of attachment to Lb. In some embodiments, G1 and G3 are each independently selected from a chemical bond and 10 the following structures: and In some embodiments, G2 and G4 are each independently the following structural fragment or a combination thereof: wherein one terminus of the wavy line marked with * is a terminus proximal to La'. In some embodiments, when n2 is 0, G2 and G3 are absent, and G4 is selected from the following structural fragments: , wherein the wavy line marked with * represents a site of attachment to G1. In some other embodiments, when n2 is not 0, G2 and G4 are both the following structural fragment: HN^ O , wherein the wavy line marked with * represents a site of attachment to G1 or G3. In some embodiments, each Lb is independently selected from a chemical bond and C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -(CO)-, -NH-, -(C=S)-, and C6-10 arylene, wherein the alkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl. In some specific embodiments, each Lb is independently selected from a chemical bond, , and wherein the wavy line marked with * represents a site of attachment to D, and the wavy line represents a site of attachment to G, G2, or G4. In some embodiments, Lc is a chemical bond. In some other embodiments, Lc is * H u h , wherein the wavy line marked with * represents a site of attachment to Q, and the wavy line represents a site of attachment to G, G2, or G4. In some embodiments, Q is a small-molecule binder. In some other embodiments, each Q is , , , , , , N H , and independently selected from the following structures: , wherein R1 is selected from H, C1-6 alkyl, halogen, methoxy, and trifluoromethyl; preferably, R1 is selected from methyl and iodine; Ra1 to Ra11 are each independently selected from hydrogen, C1-6 alkyl, C1-6 alkoxy, halogen, cyano, nitro, amino, and hydroxyl. In some specific embodiments, each Q is independently selected from and In some embodiments, each D is independently selected from: bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (CBTE2a), cyclohexyl-1,2- diaminetetraacetic acid (CDTA), 4-(1,4,8,11-tetraazacyclotetradec-1-yl)-methylbenzoic acid (CPTA), N'-[5-[acetyl(hydroxy)amino]pentyl]-N-[5-[[4-[5-aminopentyl-(hydroxy)amino]-4-oxobutanoyl]amino]pentyl]-N-hydroxybutanediamide (DFO), 4,11-bis(carboxymethyl)- 1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (DO2A), 1,4,7,10-tetraazacyclododecane-N, N, N",N"’-tetraacetic acid (DOTA), a-(2-carboxyethyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTAGA), 1,4,7,10- azacyclododecane-N,N',N'',N'''-1,4,7,10-tetra(methylene)phosphonic acid (DOTMP), N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5''-bis(phosphate) (DPDP), diethylenetriamine-N,N',N''-penta(methylene)phosphonic acid (DTMP), diethylenetriaminepentaacetic acid (DTPA), ethylenediamine-N,N'-tetraacetic acid (EDTA), ethylene glycol-O,O-bis(2- aminoethyl)-N,N,N'',N''-tetraacetic acid (EGTA), N,N-bis(hydroxybenzyl)-ethylenediamine-N,N''-diacetic acid (HBED), hydroxyethylethylenediaminetriacetic acid (HEDTA), 1-(p-nitrobenzyl)-1,4,7,10-tetraazacyclodecane-4,7,10-triacetate (HP-DOA3), 6-hydrazinyl-N- methylpyridine-3-carboxamide (HYNIC), tetra 3-hydroxy-N-methyl-2-pyridone chelator abbreviated as Me-3,2-HOPO (4-((4-(3-(bis(2-(3-hydroxy-1-methyl-2-oxo-1,2- dihydropyridine-4-carboxamido)ethyl)amino)-2-((bis(2-(3-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamido)ethyl)amino)methyl)propyl)phenyl)amino)-4-oxobutanoic acid), 1,4,7-triazacyclononane-1-succinic acid-4,7-diacetic acid (NODASA), 1-(1-carboxy-3-carboxypropyl)-4,7-(carboxy)-1,4,7-triazacyclononane (NODAGA), 1,4,7-triazacyclononanetriacetic acid (NOTA), 4,11-bis(carboxymethyl)-1,4,8,11- tetraazabicyclo[6.6.2]hexadecane (TE2A), 1,4,8,11-tetraazacyclododecane-1,4,8,11-tetraacetic acid (TETA), tris(hydroxypyridone) (THP), terpyridine-bis(methyleneaminetetraacetic acid) (TMT), 1,4,7-triazacyclononane-1,4,7-tris[methylene(2-carboxyethyl)phosphinic acid] (TRAP), 1,4,7,10-tetraazacyclotridecane-N,N',N'',N'''-tetraacetic acid (TRITA), 3-[[4,7-bis[[2- carboxyethyl(hydroxy)phosphoryl]methyl]-1,4,7-triazacyclononan-1-yl]methyl-hydroxy-phosphoryl]propanoic acid, triethylenetetraminehexaacetic acid (TTHA), and N1-(5- aminopentyl)-N1-hydroxy-N4-(5-(N-hydroxy-4-((5-(N-hydroxyacetamido)pentyl)amino)-4- oxobutanamido)pentyl)butanediamide. In some specific embodiments, each D is independently selected from 10 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, 1,4,7-triazacyclononanetriacetic acid (NOTA), and N1-(5-aminopentyl)-N1-hydroxy-N4-(5-(N-hydroxy-4-((5-(N-hydroxyacetamido)pentyl)amino)-4-oxobutanamido)pentyl)butanediamide. In some embodiments, the radionuclide is selected from any radioactive cation or anion of F, Br, I, Sc, Cu, Ga, Y, In, Lu, Tc, Sm, Sr, Ra, Tb, Ho, Re, Pb, Bi, Ac, Th, Co, Gd, Dy, Zr, At, and Er. Preferably, the radionuclide is selected from 18F, 77Br, 131I, 125I, 43Sc, 44Sc, 47Sc, 64Cu, 67Cu, 67Ga, 68Ga, 86Y, 90Y, 90In, 111In, 177Lu, 94Tc, 99Tc, 153Sm, 89Sr, 223Ra, 151Tb, 166Ho, 186Re, 188Re, 212Pb, 213Bi, 212Bi, 225Ac, 227Th, 55Co, 57Co, 152Gd, 153Gd, 157Gd, 166Dy, 89Zr, and 211At, more preferably 68Ga, 64Cu, and 177Lu. 15 In some embodiments, the compound of formula (III) has the following structure: ho2c—co2h £8 HOOC^ \—I ^COOH, and preferably, 5 COoH , NH COOH NH cooh, and HOOC COOH HOOC COOH . N In one specific embodiment, j is 1, k is 1, La' is (Gly)3-, Lb is H H N , , Lc is a chemical one specific embodiment, the compound of formula (III) has the following structure: Lc is a chemical bond, G is In one specific embodiment, j is 1, k is 1, La' is (Gly)3-, Lb is D is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is 10 following structure: .In one specific embodiment, the compound of formula (III) has the Cl ho2c—co2h bond, G is Lc is a chemical In one specific embodiment, j is 1, k is 1, La' is (Gly)3-, Lb is D is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is one specific embodiment, the compound of formula (III) has the following structure: In one specific embodiment, j is 1, k is 1, La’ is (Gly)3-, Lb is h , Lc is a chemical bond, G is , D is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is 0 .In one specific embodiment, the compound of 10 formula (III) has the following structure: h2n co2h ho2c co2h H H,N In one specific embodiment, j is 1, k is 1, La' is (Gly)3-, Lb is h , Lc is a chemical HN one specific embodiment, the compound of formula (III) has the following structure: . CO2H N In one specific embodiment, j is 1, k is 1, La' is (Gly)3-, Lb is , Lc is a chemical one specific embodiment, the compound of formula (III) has the following structure: li H 9 H2N. X X 2 N Y N H H H 10 HN O COOH HOOC—1 COOH In one specific embodiment, j is 1, k is 1, La' is (Gly)3-, Lb is a chemical bond, Lc is a chemical bond, G is HN^ , D is 1,4,7,10-tetraazacyclododecane- N, N, N", N"'-tetraacetic acid, and Q is " .In one specific embodiment, the compound of formula (III) has the following structure: H n H H,N Y N Y 0 0 A H S O H NH In one specific embodiment, j is 1, k is 2, La' is (Gly)3-, Lb is h , Lc is a chemical 10 # # bond, G is N, N, N", N"'-tetraacetic acid, and Q is " is 1,4,7,10-tetraazacyclododecane- , D .In one specific embodiment, the compound of formula (III) has the following structure: In one specific embodiment, j is 1, k is 1, La' is (Gly)3-, Lb is Lc is HN^ another embodiment, j is 1, k is 1, La' is (Gly)3-, Lb is a chemical bond, Lc is a chemical bond, G is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is . In one specific embodiment, the compound of formula (III) has the following structure: H N N. X N H HOOC—COOH S S H V In one specific embodiment, j is 1, k is 1, La' is (Gly)3-, Lb is # HrA H , Lc is 10 a chemical bond, G is H * l-N. , '0' II - H JI 0 \ 0 HN^ , D is N1-(5-aminopentyl)- N1- hydroxy-N4-(5-(N-hydroxy-4-((5-(N-hydroxyacetamido)pentyl)amino)-4- h2n oxobutanamido)pentyl)butanediamide, and Q is .In one specific embodiment, the compound of formula (III) has the following structure: .. o In one specific embodiment, j is 1, k is 1, La' is (Gly)3-, Lb is , Lc embodiment, the compound of formula (III) has the following structure: h2n 10 H SN In one specific embodiment, j is 1, k is 1, La' is NH2-(CH2)4-(CO)-, Lb is # HN^ N H , Lc one specific embodiment, the compound of formula (III) has the following structure: 0 H .^N In one specific embodiment, j is 1, k is 1, La' h , Lc is a chemical bond, G is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is .In one specific embodiment, the compound of formula (III) has the following structure: HN^ * In one specific embodiment, j is 1, k is 1, La' is , Lb is one specific embodiment, the compound of formula (III) has the following structure: COoH . In one specific embodiment, j is 1, k is 1, La' is (Gly)3-, Lb is a chemical bond, Lc is a chemical # HN^ '0' bond, G is HN^ , D is 1,4,7,10-tetraazacyclododecane- COOH SO.H N,N',N'',N'''-tetraacetic acid, and Q is specific embodiment, the compound of formula (III) has the following structure: 0 . In one specific embodiment, j is 1, k is 1, La' is (Gly)3-, Lb is # HN% , Lc is a chemical 10 0 bond, G is 1,4,7,10-tetraazacyclododecane- N,N,N",N"'-tetraacetic acid, and Q is ' - .In one specific embodiment, the compound of formula (III) has the following structure: 10 COOH HOOC bond, G is H In one specific embodiment, j is 1, k is 1, La' is (Gly)3-, Lb is # 1,4,7,10-tetraazacyclododecane- N, N, N", N"'-tetraacetic acid, and Q is " compound of formula (III) has the following structure: h ? h A _O. ,O. H,N Y N Y O — O H COOH h , Lc is a chemical .In one specific embodiment, the HN O COOH N N HOOC—\--1 COOH Another aspect of the present disclosure provides a compound comprising a structure of formula (II') below: wherein formula (II'), 15 Q is an albumin-binding unit; D and D' are each independently a chelating group for a radionuclide; Ld is selected from a chemical bond and C1-60 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with a substituent selected from -O-, -NH-, and -(CO)-; L1, L2, and each L1' and L2' are each independently a chemical bond or an amino acid fragment with a degree of polymerization of 1-10, or selected from one or a combination of the following divalent groups: C1-10 alkylene, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, nitro, cyano, and C1-10 alkyl; m is an integer selected from 0 to 20; n is an integer selected from 2 to 20. In some embodiments, Ld is selected from a chemical bond, -NH-C1-20 alkylene-(CO)-, and -NH-(PEG)i-(CO)-, wherein (PEG)i comprises 1-20 structural units selected from -(O-C2H4)-and -(C2H4-O)-, and is optionally linked to C1-10 alkylene at at least one terminus of the -(O-C2H4)- or -(C2H4-O)- structural unit. In some embodiments, i is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20. In some embodiments, Ld is -NH-(PEG)i-(CO)-, wherein (PEG)i is 1-20 consecutive -(O-C2H4)- or -(C2H4-O)- structural units, and is optionally linked to C1-10 alkylene at at least one terminus of the -(O-C2H4)- or -(C2H4-O)- structural unit; preferably, Ld is -NH-(PEG)i-C1-10 alkylene-(CO)-; more preferably, Ld is -NH-PEG4-C2H4-(CO)-, -NH-PEG3-C2H4-(CO)-, or -NH-PEG4-C3H6-(CO)-; further preferably, Ld is -NH-(C2H4-O)4-C2H4-(CO)-. In some embodiments, Ld is -NH-(PEG)i-C1-10 alkylene-(CO)-, wherein i is an integer selected from 1 to 12; preferably, i is 2, 3, 4, 5, or 6; more preferably, i is 4. In some embodiments, Ld is -NH-PEG4-(CO)-. In some embodiments, L1 and L1' are each independently selected from any one of a chemical bond, C1-10 alkylene, -NH-, and -(CO)-, or any combination thereof; preferably, L1 is selected from -(CH2)4-NH-, -CO-NH-C2H4-NH-, and -NH-, and L1' is selected from a chemical bond, -(CH2)4-NH-, -CO-NH-C2H4-NH-, and -NH-. In some embodiments, L1 and L1' are identical. In some embodiments, L2 and L2' are each independently selected from any one of a chemical bond, an amino acid fragment with a degree of polymerization of 1-10, -(CO)-, C1-10 alkylene, and -NH-, or any combination thereof; preferably, L2 is selected from -(CO)-, -(CH2)4-NH-, -CO-amino acid fragment with degree of polymerization of 1-10-, and -CO-Lys-, and L2' is selected from a chemical bond, -(CO)-, -(CH2)4-NH-, -CO-amino acid fragment with degree of polymerization of 1-10-, and -CO-Lys-. In some embodiments, L1 and L1' are identical. In some embodiments, m is an integer selected from 0 to 10; preferably, m is 0, 1, or 2; more preferably, m is 0 or 1. In some embodiments, n is an integer selected from 2 to 10; preferably, n is 2, 3, or 4; more preferably, n is 3. In some embodiments, D and D' are each independently selected from bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (CBTE2a), cyclohexyl-1,2-diaminetetraacetic acid (CDTA), 4-(1,4,8,11-tetraazacyclotetradec-1-yl)-methylbenzoic acid (CPTA), N'-[5-[acetyl(hydroxy)amino]pentyl]-N-[5-[[4-[5-aminopentyl-(hydroxy)amino]-4-oxobutano yl]amino]pentyl]-N-hydroxybutanediamide (DFO), 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (DO2A), 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA), a-(2-carboxyethyl)-1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid (DOTAGA), 1,4,7,10-azacyclododecane-N,N',N'',N'''-1,4,7,10-tetra(methylene)phosphonic acid (DOTMP), N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5''-bis(phosphate) (DPDP), diethylenetriamine-N,N',N''-penta(methylene)phosphonic acid (DTMP), diethylenetriaminepentaacetic acid (DTPA), ethylenediamine-N,N'-tetraacetic acid (EDTA), ethylene glycol-O,O-bis(2-aminoethyl)-N,N,N'',N''-tetraacetic acid (EGTA), N,N-bis(hydroxybenzyl)-ethylenediamine-N,N''-diacetic acid (HBED), hydroxyethylethylenediaminetriacetic acid (HEDTA), 1-(p-nitrobenzyl)-1,4,7,10-tetraazacyclodecane-4,7,10-triacetate (HP-DOA3), 6-hydrazinyl-N-methylpyridine-3-carboxamide (HYNIC), tetra 3-hydroxy-N-methyl-2-pyridone chelator abbreviated as Me-3,2-HOPO (4-((4-(3-(bis(2-(3-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamido)ethyl)amino )-2-((bis(2-(3-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamido)ethyl)amino)met hyl)propyl)phenyl)amino)-4-oxobutanoic acid), 1,4,7-triazacyclononane-1-succinic acid-4,7-diacetic acid (NODASA), 1-(1-carboxy-3-carboxypropyl)-4,7-(carboxy)-1,4,7-triazacyclononane (NODAGA), 1,4,7-triazacyclononanetriacetic acid (NOTA), 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (TE2A), 1,4,8,11-tetraazacyclododecane-1,4,8,11-tetraacetic acid (TETA), tris(hydroxypyridone) (THP), terpyridine-bis(methyleneaminetetraacetic acid) (TMT), 1,4,7-triazacyclononane-1,4,7-tris[methylene(2-carboxyethyl)phosphinic acid] (TRAP), 1,4,7,10-tetraazacyclotridecane-N,N',N'',N'''-tetraacetic acid (TRITA), 3-[[4,7-bis[[2-carboxyethyl(hydroxy)phosphoryl]methyl]-1,4,7-triazacyclononan-1-yl]methyl -hydroxy-phosphoryl]propanoic acid, and triethylenetetraminehexaacetic acid (TTHA); preferably, D is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid; D' is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid. In some embodiments, the radionuclide is selected from any radioactive cation or anion of F, Br, I, Sc, Cu, Ga, Y, In, Lu, Tc, Sm, Sr, Ra, Tb, Ho, Re, Pb, Bi, Ac, Th, Co, Gd, Dy, Zr, At, and Er; preferably, the radionuclide is selected from 18F, 77Br, 131I, 125I, 43Sc, 44Sc, 47Sc, 64Cu, 67Cu, 67Ga, 68Ga, 86Y, 90Y, 90In, 111In, 177Lu, 94Tc, 99Tc, 153Sm, 89Sr, 223Ra, 151Tb, 166Ho, 186Re, 188Re, 212Pb, 213Bi, 212Bi, 225Ac, 227Th, 55Co, 57Co, 152Gd, 153Gd, 157Gd, 166Dy, 89Zr, and 211At, preferably 68Ga, 64Cu, and 177Lu. In some embodiments, Q is selected from represents a site attached to L2 in formula (II'), wherein R1 is selected from H, C1-6 alkyl, halogen, methoxy, and trifluoromethyl; preferably, halogen is fluorine, chlorine, bromine, or iodine; preferably, R1 is selected from methyl and iodine; Ra1 to Ra11 are each independently selected from hydrogen, C1-6 alkyl, C1-6 alkoxy, halogen, cyano, nitro, amino, and hydroxyl; preferably, halogen is fluorine, chlorine, bromine, or iodine; , 10 HOOC HOOC H h2 COOH • ; preferably, , COOH cooh , and COOH SO,H , COOH cooh , and HOOC COOH N N HOOC—\--1 COOH In some embodiments, m is 0, and the compound of formula (II') has a structure represented by formula (II''): H . _____ . N_^,L2 q Ld^ T H2N formula (II'') 10 wherein the groups are as defined for formula (II') of the present disclosure. In one specific embodiment, m is 0, n is 3, Ld is -NH-(C2H4-O)4-C2H4-(CO)-, L1 is -(CH2)4-NH-, L2 is -(CO)-, D is 1,4,7,10-tetraazacyclododecane- N,N',N'',N'''-tetraacetic acid, and Q is formula (II') has the following structure: COOH 0 0 5 . In one specific embodiment, m is 1, n is 3, Ld is -NH-(C2H4-O)4-C2H4-(CO)-, L1 and L1' are - (CH2)4-NH-, L2 and L2' are -(CO)-, D and D' are 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is 3h H2N formula (II') has the following structure: o COOH HOOC COOH In one specific embodiment, m is 0, n is 3, Ld is -NH-(C2H4-O)4-C2H4-(CO)-, L1 is -CO-NH-C2H4-NH-, L2 is -(CH2)4-NH-, D is 1,4,7,10-tetraazacyclododecane- N,N',N'',N'''-tetraacetic 10 . In one specific embodiment, the compound of formula (II') acid, and Q is " has the following structure: h2n COOH HOOC COOH . In one specific embodiment, m is 0, n is 3, Ld is -NH-(C2H4-O)4-C2H4-(CO)-, L1 is -CO-NH-C2H4-NH-, L2 is -(CH2)4-NH-, D is 1,4,7,10-tetraazacyclododecane- N,N',N'',N'''-tetraacetic 15 acid, and Q is " has the following structure: . In one specific embodiment, the compound of formula (II') In yet another aspect, the present disclosure further provides a conjugate comprising a structure of formula (III'') below: Ab (GlyV^X^Ld—X, formula (III'') wherein Ab is a targeting moiety comprising an antibody or an antigen-binding fragment thereof; preferably, the antibody is a single-domain antibody or a single-chain antibody; Gly is a glycine residue; -(PEG)i- is optionally present between the carboxyl group of any one glycine and the amino group of the other glycine, wherein (PEG)i is 1-20 consecutive -(O-C2H4)- or -(C2H4-O)- structural units, and is optionally linked to C1-10 alkylene at at least one terminus of the -(O-C2H4)- or -(C2H4-O)- structural unit; Ld is selected from a chemical bond and C1-60 alkylene, wherein the alkylene is optionally replaced with a substituent selected from -O-, -NH-, and -(CO)-; each X1 is independently lysine (Lys), and X1 is further linked to D; each X2 is independently Lys, and X2 is further linked to D' and Q; D and D' are each independently a chelating group for a radionuclide; each Q is independently an albumin-binding unit; m is an integer selected from 0 to 20; n is an integer selected from 2 to 20; z is an integer selected from 1 to 20. In some embodiments, Gly in formula (III'') of the present disclosure has the following structure: o , wherein * represents a site of attachment to Ab, and “ ” represents a site of attachment to X1 or Ld. In some embodiments, Ld is a chemical bond. In some embodiments, Ld is -NH-(PEG)i-(CO)-, wherein (PEG)i is 1-20 consecutive -(O-C2H4)- or -(C2H4-O)- structural units, and is optionally linked to C1-10 alkylene at at least one terminus of the -(O-C2H4)- or -(C2H4-O)- structural unit; preferably, Ld is -NH-(PEG)i-C1-10 alkylene-(CO)-; more preferably, Ld is -NH-PEG4-C2H4-(CO)-, -NH-PEG3-C2H4-(CO)-, or -NH-PEG4-C3H6-(CO)-; further preferably, Ld is -NH-(C2H4-O)4-C2H4-(CO)-. In some embodiments, i is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20. In some embodiments, a terminus of Ab is modified to be conjugated with -(Gly)n- in formula (III'') under the action of a ligase. In some embodiments, the ligase is a Sortase enzyme. In some embodiments, Ab comprises an antibody with a C-terminal modification or an N-terminal modification. In some embodiments, an antibody, a spacer (SP), and a recognition sequence for a ligase donor substrate are linked in sequence. In some embodiments, an antibody and a recognition sequence for a ligase donor substrate are linked in sequence. In some embodiments, the spacer is selected from GA, GGGGS, GGGGSGGGGS, and GGGGSGGGGSGGGGS; preferably, the spacer is GA. In particular, the recognition sequence for a ligase donor substrate is LPETGG. In some embodiments, the recognition sequence for a ligase donor substrate is LPX1TGX2, wherein X1 is any natural or non-natural amino acid, and X2 is absent or an amino acid fragment comprising 1-10 amino acids. In some embodiments, Ab is an anti-prostate-specific membrane antigen (PSMA) antibody; preferably, Ab is an anti-PSMA single-domain antibody. In some embodiments, Ab is an anti-epidermal growth factor receptor 2 (HER2) antibody. In still other embodiments, Ab is an antiDelta-like ligand 3 (DLL3) antibody. In some embodiments, antibody Ab comprises an HCDR1 set forth in SEQ ID NO: 1, an HCDR2 set forth in SEQ ID NO: 2, and an HCDR3 set forth in SEQ ID NO: 3. In some embodiments, antibody Ab comprises an HCDR1 set forth in SEQ ID NO: 4, an HCDR2 set forth in SEQ ID NO: 5, and an HCDR3 set forth in SEQ ID NO: 6. In some embodiments, antibody Ab comprises an HCDR1 set forth in SEQ ID NO: 7, an HCDR2 set forth in SEQ ID NO: 8, and an HCDR3 set forth in SEQ ID NO: 9. In some embodiments, antibody Ab comprises an HCDR1 set forth in SEQ ID NO: 23, an HCDR2 set forth in SEQ ID NO: 24, and an HCDR3 set forth in SEQ ID NO: 25. In some embodiments, antibody Ab comprises the amino acid sequence set forth in SEQ ID NO: 10 or SEQ ID NO: 11, or comprises the amino acid sequence set forth in positions 1 to 127 of SEQ ID NO: 12, or comprises the amino acid sequence set forth in positions 1 to 115 of SEQ ID NO: 22. In some embodiments, antibody Ab comprises an amino acid sequence having at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the amino acid sequence set forth in SEQ ID NO: 10 or SEQ ID NO: 11. In some embodiments, antibody Ab comprises an amino acid sequence having at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the amino acid sequence set forth in positions 1 to 127 of SEQ ID NO: 12. In some other embodiments, antibody Ab comprises an amino acid sequence having at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the amino acid sequence set forth in positions 1 to 115 of SEQ ID NO: 22. In some embodiments, antibody Ab comprises the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, antibody Ab comprises the amino acid sequence set forth in SEQ ID NO: 11. In some embodiments, antibody Ab comprises the amino acid sequence set forth in positions 1 to 127 of SEQ ID NO: 12. In some other embodiments, antibody Ab comprises the amino acid sequence set forth in positions 1 to 115 of SEQ ID NO: 22. In some embodiments, modified antibody Ab comprises the amino acid sequence set forth in SEQ ID NO: 12. In some embodiments, when antibody Ab is linked to Gly in formula (III''), its C-terminal amino acid sequence GGHHHHHH is cleaved by a Sortase enzyme. In some embodiments, modified antibody Ab comprises the amino acid sequence set forth in positions 1 to 133 of SEQ ID NO: 12. In some embodiments, modified antibody Ab comprises the amino acid sequence set forth in SEQ ID NO: 13. In some embodiments, when antibody Ab is linked to Gly in formula (III''), its C-terminal amino acid sequence GG is cleaved by a Sortase enzyme. In some embodiments, modified antibody Ab comprises the amino acid sequence set forth in positions 1 to 141 of SEQ ID NO: 13. In some embodiments, modified antibody Ab comprises the amino acid sequence set forth in SEQ ID NO: 22. In some embodiments, when modified antibody Ab is linked to Gly in formula (III''), its C-terminal amino acid sequence GGHHHHHH (SEQ ID NO: 19) is cleaved by a Sortase enzyme. In some embodiments, modified antibody Ab comprises the amino acid sequence set forth in positions 1 to 121 of SEQ ID NO: 22. In some embodiments, X1 has the following structure: D HN' H 0 , wherein D is as defined for formula (II') of the present disclosure. In some embodiments, X2 has a structure of formula (IV-1) below: D’ HN' L2—Q H o formula (IV-1) wherein D', L2, and Q are as defined for formula (II') of the present disclosure. In some embodiments, X2 has a structure of formula (IV-2) below: ,Q HN s -1 — 0’ s N H o formula (IV-2) wherein D', L1, and Q are as defined for formula (II') of the present disclosure. In some embodiments, L1 is -NHCH2CH2NH-. In some embodiments, in formula (III'') of the present disclosure, m is 0, z is 1, Ld is -NH-(C2H4-O)i-C2H4-(CO)-, and X2 is formula (IV-1), which has a structure of formula (V-1): D' HN^ L2----Q O H O O Ab / LPET. R NY A \„.Y N Y N Y Y NH GA H q H q ' formula (V-1) wherein Ab is as defined for formula (III'') of the present disclosure; i, D', L2, and Q are as defined for formula (II') of the present disclosure. In some embodiments, L2 is -NHCH2CH2NH-. In some embodiments, in formula (III'') of the present disclosure, m is 0, z is 1, Ld is -NH- (C2H4-O)i-C2H4-(CO)-, and X2 is formula (IV-2), which has a structure of formula (V-2): ,Q HN AbY ALPET\ A >\JL OL1--D' >4 / N A N Y v °7i NH \\ H O H 0 0 formula (V-2) wherein Ab is as defined for formula (III'') of the present disclosure; i, D', L1, and Q are as defined for formula (II') of the present disclosure. In yet another aspect, the present disclosure provides a compound having a structure of formula (III'''): (Gly)n-(-xALd—X2 formula (III''') wherein X1, X2, Ld, n, and z are as defined for formula (III'') of the present disclosure. In yet another aspect, the present disclosure relates to a radionuclide conjugate comprising a radionuclide conjugate of formula (I), (I'), (I''), (II), or (III'') and a radionuclide. <A Targeting Moiety ( ^l, A, or Ab) In the conjugate of the present disclosure, A is a targeting moiety targeting a specific target. Inclusion of the targeting moiety in the conjugate of the present disclosure enables an excellent cell / tissue-targeting function to be achieved. The “targeting moiety” refers to a moiety that has affinity for a specific target (e.g., a receptor, a cell-surface protein, a cytokine, and a tumorspecific antigen). The targeting molecule can deliver the payload to a specific site in vivo by targeted delivery. The targeting moiety can recognize one or more targets. The specific target sites are defined by the target it recognizes. For example, a targeting moiety targeting a receptor can deliver the radionuclide-chelating moiety to sites abundant with the receptor. In some embodiments, A is a targeting moiety targeting a prostate-specific membrane antigens (PSMA). PSMA is expressed on malignant cancer cells. As used herein, the term “cancer” refers to a neoplasm characterized by uncontrolled and usually rapidly-proliferating cells that tend to invade surrounding tissues and metastasize to distant body sites; it includes both benign and malignant neoplasms. Malignant tumors of cancers are generally characterized by anaplasia, infiltration, and metastasis, while benign tumors generally do not possess those properties. Specifically, PSMA may optionally be highly expressed in prostate cancer cells, pancreatic cancer cells, renal cancer cells, or bladder cancer cells. The presence of PSMA-expressing cells or tissues can indicate prostate tumor (cells), metastatic prostate tumor (cells), renal tumor (cells), pancreatic tumor (cells), bladder tumor (cells), and combinations thereof. Thus, the radionuclide conjugates, pharmaceutical compositions, and kits of the present disclosure may be used for diagnosing, and optionally delaying or treating prostate cancer, renal cancer, pancreatic cancer, or bladder cancer. In some other embodiments, A is a targeting moiety targeting epidermal growth factor receptor 2 (HER2). In still other embodiments, A is a targeting moiety targeting Delta-like ligand 3 (DLL3). In one embodiment, A is a targeting moiety comprising an antibody or an antigen-binding fragment thereof, wherein the antibody is a single-domain antibody. Linker Compound and Linker Compound Fragment In addition to the targeting moiety (A), the conjugate of the present disclosure further comprises a payload unit having a structure of formula (III): J k formula (III) wherein each Q is independently an albumin-binding unit; each D is independently a chelating group for a radionuclide; La' is selected from the following 1), 2), and a combination thereof: 1) one or more natural or non-natural amino acids or oligomeric natural or non-natural amino acids with a degree of polymerization of 2-20; 2) C1-20 alkyl, wherein a carbon chain unit of the alkyl is optionally replaced with at least one substituent selected from -O-, -S-, -NH-, -(CO)-, C2-6 alkynyl, C3-10 cycloalkylene, 3- to 10membered heterocycloalkylene, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, alkynyl, cycloalkylene, heterocycloalkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, sulfonyl-C1-10 alkyl, and 3- to 10-membered heterocycloalkyl; each Lb and each Lc, when present, is independently a chemical bond or C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -(CO)-, -NH-, -(C=S)-, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; G is a branching moiety with a branching function, and is directly or indirectly linked to Q and D, wherein each G is independently selected from the following 3), 4), and a combination thereof: 3) one or more natural or non-natural amino acids or oligomeric natural or non-natural amino acids with a degree of polymerization of 2-20; 4) a chemical bond or C1-60 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; j is an integer selected from 1 to 30; k is an integer selected from 1 to 20. In some embodiments, in addition to the targeting moiety (A), the conjugate of the present disclosure further comprises a payload-linker moiety (LP), which has a structure of formula 1-2-. Ld m Li formula (II'), wherein Q is an albumin-binding unit; D and D' are each independently a chelating group for a radionuclide; A is a targeting moiety comprising an antibody or an antigen-binding fragment thereof; preferably, the antibody is selected from a single-domain antibody and a single-chain antibody; Ld is selected from a chemical bond and C1-60 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-; L1, L2, L1', and L2' are each independently a chemical bond or an amino acid fragment with a degree of polymerization of 1-10, or selected from one or a combination of the following divalent groups: C1-10 alkylene, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, nitro, cyano, and C1-10 alkyl; m is an integer selected from 0 to 20; n is an integer selected from 2 to 20. In some embodiments, the radionuclide conjugate of the present disclosure further comprises a compound fragment having a structure of formula (V): wherein formula (V) each Lb is covalently linked to a chelating group, and each Lc is covalently linked to an albuminbinding unit; each Lb and each Lc, when present, is independently a chemical bond or C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -(CO)-, -NH-, -(C=S)-, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; G is a branching moiety with a branching function, wherein G is selected from the following 1), 2), and a combination thereof: 1) one or more natural or non-natural amino acids or oligomeric natural or non-natural amino acids with a degree of polymerization of 2-20; 2) a chemical bond or C1-60 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; j is an integer selected from 1 to 30, preferably an integer of 1-10, and more preferably an integer of 1-5; k is an integer selected from 1 to 20, preferably an integer of 1-10, and more preferably an integer of 1-5. In some embodiments, the albumin-binding unit is a small molecule. In some embodiments, the radionuclide conjugate of the present disclosure further comprises a compound fragment having a structure of formula (VI): wherein formula (VI) each Lb is covalently linked to a chelating group, and each Lc is covalently linked to an albuminbinding unit; each Lb and each Lc, when present, is independently a chemical bond or C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -(CO)-, -NH-, -(C=S)-, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; each G1 or G3, when present, is independently selected from a chemical bond and C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; preferably, each G1 or G3, when present, is independently selected from a chemical bond, optionally substituted -NH-(C1-10 alkylene)-CO-, optionally substituted -NH-PEG-CO-, optionally substituted -NH-PEG-(C1-10 alkylene)-CO-, and optionally substituted -NH-(C1-10 alkylene)-PEG-CO-; the substituent for the substitution is selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl-; PEG is -(CH2CH2O)x- or -(OCH2CH2)y-, and x or y is an integer of 1-20; each G2 or G4, when present, is independently a branching unit; preferably, each G2 or G4 is selected from one of or a combination of more of the following groups: 1) one or more branched natural or non-natural amino acid fragments, wherein preferably, the branched natural or non-natural amino acid fragment has the following structure: -NH-(CR2R3)-CO-, wherein R2 and R3 are each independently selected from hydrogen, optionally substituted -(C1-10 alkylene)-NH-, and optionally substituted -(C1-10 alkylene)-CO-; R2 and R3 are not simultaneously hydrogen; more preferably, the branched natural or non-natural amino acid is a glutamic acid fragment, an aspartic acid fragment, or a lysine fragment; the substituent for the substitution is selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl-; 2) C1-20 linear or branched alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; n1 and n2 are each independently an integer of 0-10, preferably an integer of 0-5, such as 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; 10 j1, j2, k1, and k2 are each independently an integer of 0-10, preferably an integer of 0-5, such as 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some embodiments, the albumin-binding unit is a small molecule. In some embodiments, the chelating group and the albumin-binding unit are as defined herein. In some embodiments, G is selected from the following structures: 15 # HN% 9 , and wherein g is an integer selected from 1 to 20, preferably an integer of 1-5, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20; preferably, HN^ * N 0 0 HN— s ° 5 L Jg # HN% >< hn^y n V A H o L u Jg , , C H H ? * / N^o^O^o^O^vN_Ar J Hh # HN^ H H H I H j f H 0 H 0 , ^^OH si N d H Jg y , # i\A 9 , and HN^ wherein g is an integer selected from 1 to 20, preferably an integer of 1-5, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20; 5 more preferably, and further preferably, , and wherein the wavy line marked with # represents a site of attachment to Lc or Lb, and the wavy line represents a site of attachment to Lb or Lc. In some embodiments, G1 and G3 are each independently selected from a chemical bond and the following structures: and In some embodiments, G2 and G4 are each independently the following structural fragment or a combination thereof: HN% O , and 0 wherein one terminus of the wavy line marked with * is a terminus proximal to G1 or G3. In some embodiments, when n2 is 0, G2 and G3 are absent, and G4 is selected from the following 10 structural fragments: In some other embodiments, when n2 is not 0, G2 and G4 are both the following structural fragment: HN% 15 0 , wherein the wavy line marked with * represents a site of attachment to G1 or G3. In some specific embodiments, each Lb is independently selected from the following structures: a chemical bond; * , wherein the wavy line marked with * represents a site of attachment to the 20 chelating group, and the wavy line represents a site of attachment to G, G2, or G4; H S S H H \= / H , wherein the wavy line marked with * represents a site of attachment to the chelating group, and the wavy line represents a site of attachment to G, G2, or G4; or H H \= / , wherein the wavy line marked with * represents a site of attachment to the chelating group, and the wavy line represents a site of attachment to G, G2, or G4. In some specific embodiments, Lc is a chemical bond; or '■ h , wherein the wavy line marked with * represents a site of attachment to the albumin-binding unit, and the wavy line represents a site of attachment to G, G2, or G4. In some embodiments, the radionuclide conjugate of the present disclosure comprises a compound fragment having a structure of formula (III'): wherein formula (III'), Ld is selected from a chemical bond and C1-60 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-; L1, L2, and each L1' and L2' are each independently covalently linked to a chelating group or an albumin-binding unit; L1, L2, and each L1' and L2' are each independently a chemical bond or an amino acid fragment with a degree of polymerization of 1-10, or selected from one or a combination of the following divalent groups: C1-10 alkylene, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, nitro, cyano, and C1-10 alkyl; m is an integer selected from 0 to 20. In some embodiments, Ld is selected from a chemical bond, -NH-C1-20 alkylene-(CO)-, and -NH-(PEG)i-(CO)-, wherein (PEG)i comprises 1-20 structural units selected from -(O-C2H4)-and -(C2H4-O)-, and is optionally linked to C1-10 alkylene at at least one terminus of the -(O-C2H4)- or -(C2H4-O)- structural unit. In some embodiments, Ld is -NH-(PEG)i-C1-10 alkylene-(CO)-, wherein i is an integer selected from 1 to 12; preferably, i is 2, 3, 4, 5, or 6; more preferably, i is 4. In some specific embodiments, Ld is -NH-(PEG)i-(CO)-, wherein (PEG)i is 1-20 consecutive -(O-C2H4)- or -(C2H4-O)- structural units, and is optionally linked to C1-10 alkylene at at least one terminus of the -(O-C2H4)- or -(C2H4-O)- structural unit. In some preferred embodiments, Ld is -NH-(PEG)i-C1-10 alkylene-(CO)-. In one more preferred embodiment, Ld is -NH-PEG4-C2H4-(CO)-. In a further preferred embodiment, Ld is -NH-(C2H4-O)4-C2H4-(CO)-. In some embodiments, L1 and L1' are each independently covalently linked to the chelating group, and L2 and L2' are each independently covalently linked to the albumin-binding unit. In some embodiments, the albumin-binding unit is a small molecule. In some embodiments, L1 and L1' are each independently selected from any one of a chemical bond, C1-10 alkylene, -NH-, and -(CO)-, or any combination thereof. In some preferred embodiments, L1 is selected from -(CH2)4-NH-, -CO-NH-C2H4-NH-, and -NH-. In some other preferred embodiments, L1' is selected from a chemical bond, -(CH2)4-NH-, -CO-NH-C2H4-NH-, and -NH-. In some embodiments, L2 and L2' are each independently selected from any one of a chemical bond, an amino acid fragment with a degree of polymerization of 1-10, -(CO)-, C1-10 alkylene, and -NH-, or any combination thereof. In some preferred embodiments, L2 is selected from -(CO)-, -(CH2)4-NH-, -CO-an amino acid fragment with a degree of polymerization of 1-10-, and -CO-Lys-; preferably, L2 is -CO-Lys-. In some other preferred embodiments, L2' is selected from a chemical bond, -(CO)-, -(CH2)4-NH-, -CO-an amino acid fragment with a degree of polymerization of 1-10-, and -CO-Lys-; preferably, L2' is -CO-Lys-. In some embodiments, m is an integer selected from 0 to 10; preferably, m is 0, 1, or 2; more preferably, m is 0 or 1. In some embodiments, n is an integer selected from 2 to 10; preferably, n is 2, 3, or 4; more preferably, n is 3. In some embodiments, the radionuclide conjugate of the present disclosure comprises a compound fragment having a structure of formula (VII): RC formula (VII) wherein Ld' is selected from C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-; RA and RB are each independently optionally linked to a chelating group and / or an albuminbinding unit; RA and RB are each independently selected from hydrogen and one or a combination of the following groups: C1-10 alkylene, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, nitro, cyano, and C1-10 alkyl; RA and RB are not simultaneously hydrogen; RC is optionally covalently linked to a chelating group, an albumin-binding unit, or a combination thereof; RC is selected from one or a combination of the following: hydroxyl, a natural or non-natural amino acid fragment, and C1-30 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NR4-, -(CO)-, -(C=S)-, and C6-10 arylene, and the alkylene and arylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; R4 is selected from hydrogen and C1-10 alkyl, wherein a carbon chain unit of the alkyl is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, and the alkyl is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl. In some embodiments, the albumin-binding unit is a small molecule. In some embodiments, Ld' is selected from -(PEG)i- and C1-10 alkylene, wherein (PEG)i is 1-10 consecutive -(O-C2H4)- or -(C2H4-O)- structural units, and is optionally linked to C1-10 alkylene at at least one terminus of the -(O-C2H4)- or -(C2H4-O)- structural unit. In one preferred embodiment, Ld' is selected from -(C2H4-O)4-C2H4- and C5 alkylene. In some embodiments, RA and RB are each independently selected from hydrogen and C1-10 alkylene, wherein the alkylene is substituted with at least one substituent selected from hydroxyl, halogen, amino, nitro, cyano, and C1-10 alkyl; RA and RB are not simultaneously hydrogen. In some preferred embodiments, RA and RB are each independently hydrogen or C1-10 alkylene, wherein the alkylene is substituted with amino; RA and RB are not simultaneously hydrogen. In some more preferred embodiments, RA and RB H are each independently hydrogen or hydroxyl, HN" 0 RC is selected from In some embodiments, HN'\ N N' N H H N . In some embodiments, formula (VII) is selected from the following structures: NH^- OH and s H 4n^o HN O H N. <> N-f-H * and preferably, 5 and In some embodiments, the present disclosure further provides a radionuclide conjugate comprising a structure of formula (V'): formula (V') wherein 10 each Q is independently an albumin-binding unit; each D is independently a chelating group for a radionuclide; each Lb and each Lc, when present, is independently a chemical bond or C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -(CO)-, -NH-, -(C=S)-, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; G is a branching moiety with a branching function, and is directly or indirectly linked to Q and D, wherein each G is independently selected from the following 1), 2), and a combination thereof: 1) one or more natural or non-natural amino acids or oligomeric natural or non-natural amino acids with a degree of polymerization of 2-20; 2) a chemical bond or C1-60 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; j is an integer selected from 1 to 30; k is an integer selected from 1 to 20. In some embodiments, the present disclosure further provides a radionuclide conjugate comprising a structure of formula (VI'): wherein each Q is independently an albumin-binding unit; preferably, the albumin-binding unit is a small-molecule albumin-binding unit; each D is independently a chelating group for a radionuclide; each Lb and each Lc, when present, is independently a chemical bond or C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -(CO)-, -NH-, -(C=S)-, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; each G1 or G3, when present, is independently selected from a chemical bond and C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; each G2 or G4, when present, is independently a branching unit; preferably, each G2 or G4 is selected from one of or a combination of more of the following groups: 1) one or more branched natural or non-natural amino acid fragments, wherein preferably, the branched natural or non-natural amino acid fragment has the following structure: -NH-(CR2R3)-CO-, wherein R2 and R3 are each independently selected from hydrogen, optionally substituted -(C1-10 alkylene)-NH-, and optionally substituted -(C1-10 alkylene)-CO-; R2 and R3 are not simultaneously hydrogen; more preferably, the branched natural or non-natural amino acid is a glutamic acid fragment, an aspartic acid fragment, or a lysine fragment; the substituent for the substitution is selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl-; 2) C1-20 linear or branched alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; n1 and n2 are each independently an integer of 0-10; j1, j2, k1, and k2 are each independently an integer of 0-10. In some embodiments, formula (V') is selected from the following structures: X 0 O Y o NH' H / Xz'H 2 ,N. / ,0. / / \ ,0. HN Y 0 H preferably, / H „ „ HN—L _N_ / if S 0 HN' x H _ _ HN—L -N„ if 0 ° 5 0 x . H HN—L N J*- ^N^o^ / O^o / ^Ox^y "Y ho2c- I XT ' .. ^NH Z \ / \ / -COOH r \ N 1100( \—1 cooi i , and / 1 l^XT o ^n^3 / \^cooh H ^N N ^N N^ 11()()( -'' ---1 ^COOH • ; jl jOtt HN^VX^^ z I Y If H nn' 5 ° H r z ^N N^ ho2c—co2h , Cl z Zr o \ —\J—\ / — co2h H NN ^N N^ ho2c—CO2H , 0 o Z—U--( / —co2h H NN n ,x N ^N N^ ho2c—co2h , —\ / ---1 / —co2h f f N N —co2h , 5 cooh, and HOOC HOOC COOH . In some embodiments, the present disclosure further provides a radionuclide conjugate comprising a structure of formula (VII'): formula (VII') wherein Ld' is selected from C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-; RA', RB', and RC' each independently optionally comprise a chelating group and / or an albumin binding unit; RA' and RB' are each independently selected from hydrogen or comprise one or a combination of the following groups: C1-10 alkyl, -NH-, and -(CO)-, wherein the alkyl is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, nitro, cyano, and C1-10 alkyl; RA' and RB' are not simultaneously hydrogen; RC' is selected from one or a combination of the following: hydroxyl, a natural or non-natural amino acid fragment, and C1-30 alkyl, wherein a carbon chain unit of the alkyl is optionally replaced with at least one substituent selected from -O-, -NR4-, -(CO)-, -(C=S)-, and C6-10 arylene, and the alkyl and arylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; R4 is selected from hydrogen and C1-10 alkyl, wherein a carbon chain unit of the alkyl is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, and the alkyl is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl. In some embodiments, the present disclosure provides a radionuclide conjugate comprising a structure of formula (II'''): wherein formula (II'''), Q is an albumin-binding unit; D and D' are each independently a chelating group for a radionuclide; Ld is selected from a chemical bond and C1-60 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-; L1, L2, and each L1' and L2' are each independently a chemical bond or an amino acid fragment with a degree of polymerization of 1-10, or selected from one or a combination of the following divalent groups: C1-10 alkylene, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, nitro, cyano, and C1-10 alkyl; m is an integer selected from 0 to 20. The pharmacological effects of the radionuclide conjugates require them to have a suitable halflife and intratumoral retention time. For example, for drugs using small molecules and polypeptides as targeting carriers, their blood clearance is too rapid, leading to excretion from the body before sufficient enrichment in the tumor; insufficient enrichment of the drugs in the tumor and a short intratumoral retention time result in a non-durable therapeutic effect. Due to the large molecular size of monoclonal antibodies, radionuclide conjugates using monoclonal antibodies as targeting carriers penetrate slowly into tissues and tumors, thereby affecting their enrichment amount in the tumor; in addition, they have long exposure time in blood circulation and normal tissues, which causes more blood toxicity and off-target toxicity. Compared with the prior art, the radionuclide conjugate of the present disclosure can achieve a suitable blood circulation half-life through the combination of a suitable targeting moiety and an albuminbinding unit, thereby increasing its tumor enrichment amount and extending its intratumoral retention time. The radionuclide conjugate of the present disclosure exhibits higher anti-tumor activity at the same dose or even lower doses; meanwhile, it does not exhibit any significant toxicity, thereby greatly broadening the potential therapeutic window of such RDC drugs. Multiple site-specific enzymatic conjugations and chemical conjugations further broaden the selection of therapeutic targets for RDC drugs. Albumin-Binding Unit (Q) In the conjugate of the present disclosure, Q is an albumin-binding unit, particularly one specifically binding to human serum albumin (HSA). Human serum albumin (HSA) is an abundant protein in human plasma. The term “human serum albumin” or “HSA” as used herein preferably refers to serum albumin encoded by the human ALB gene or a functional variant, isotype, fragment, or derivative thereof. Without wishing to be bound by a particular theory, it is believed that the albumin-binding unit (Q) in the conjugate of the present disclosure may preferably extend the circulation half-life of the radionuclide conjugate and affect its partitioning in the blood, improving delivery to target cells or tissues. Therefore, the presence of the albumin-binding unit (Q) improves the pharmacokinetic properties of the radionuclide conjugate of the present disclosure and preferably does not interfere with (reduce or eliminate) the desired function of the chelating group and the targeting moiety. The albumin-binding unit may generally bind to albumin (e.g., HSA) with a relatively high affinity, and non-covalent binding is preferred. For example, the albumin-binding unit may preferably non-covalently bind to the albumin with a binding affinity of less than about 100 pM, such as about 3-50 pM. In one embodiment, the albumin-binding unit may preferably comprise linear and branched lipophilic groups; for example, it may comprise 1-40 carbon atoms and distal acidic groups. In some embodiments, Q is an HSA small-molecule binder. In some other embodiments, each Q is independently selected from the following structures: 5 , , , , , , ; N H , and ho3 Cl , wherein 10 R1 is selected from H, C1-6 alkyl, halogen, methoxy, and trifluoromethyl; preferably, R1 is selected from methyl and iodine; Ra1 to Ra11 are each independently selected from hydrogen, C1-6 alkyl, C1-6 alkoxy, halogen, cyano, nitro, amino, and hydroxyl; preferably, Q is selected from and and ; the wavy line represents a site attached to L2 in formula (II), wherein R1 is selected from H, C1-6 alkyl, halogen, methoxy, and trifluoromethyl; preferably, halogen is fluorine, chlorine, bromine, or iodine; preferably, R1 is selected from methyl and iodine; Ra1 to Ra11 are each independently selected from hydrogen, C1-6 alkyl, C1-6 alkoxy, halogen, cyano, nitro, amino, and hydroxyl; preferably, halogen is fluorine, chlorine, bromine, or iodine. In one specific embodiment, Q is selected from Chelating Group for Radionuclide (D and D') In the conjugate of the present disclosure, D and D' are each independently a chelating group for a radionuclide. In some embodiments, D and D' are identical. The terms “chelator”, “chelating group”, and “chelating moiety” are used interchangeably herein and refer to a ligand capable of forming two or more coordination bonds with a central (metal) ion. One or more molecules that share one electron pair may also be referred to as “Lewis bases”. The central (metal) ion is generally coordinated to the chelator through two or more electron pairs. In general, the electron pair of the chelator forms coordination bonds with a single central (metal) ion; however, in certain cases, the chelator may form coordination bonds with more than one metal ion, and multiple modes of binding are possible. The term “coordination” refers to an interaction in which one multi-electron pair donor coordinately binds to a central (metal) ion, that is, sharing two or more unshared electron pairs with a central (metal) ion. The chelator is preferably selected based on its ability to coordinate the desired central (metal) ion, which, in one embodiment, is the radionuclide described herein. In one embodiment, the chelating group for a radionuclide is selected from bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (CBTE2a), cyclohexyl-1,2-diaminetetraacetic acid (CDTA), 4-(1,4,8,11-tetraazacyclotetradec-1-yl)-methylbenzoic acid (CPTA), N'-[5-[acetyl(hydroxy)amino]pentyl]-N-[5-[[4-[5-aminopentyl-(hydroxy)amino]-4-oxobutano yl]amino]pentyl]-N-hydroxybutanediamide (DFO), 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (DO2A), 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA), a-(2-carboxyethyl)-1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid (DOTAGA), 1,4,7,10-azacyclododecane-N,N',N'',N'''-1,4,7,10-tetra(methylene)phosphonic acid (DOTMP), N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5''-bis(phosphate) (DPDP), diethylenetriamine-N,N',N''-penta(methylene)phosphonic acid (DTMP), diethylenetriaminepentaacetic acid (DTPA), ethylenediamine-N,N'-tetraacetic acid (EDTA), ethylene glycol-O,O-bis(2-aminoethyl)-N,N,N'',N''-tetraacetic acid (EGTA), N,N-bis(hydroxybenzyl)-ethylenediamine-N,N''-diacetic acid (HBED), hydroxyethylethylenediaminetriacetic acid (HEDTA), 1-(p-nitrobenzyl)-1,4,7,10-tetraazacyclodecane-4,7,10-triacetate (HP-DOA3), 6-hydrazinyl-N-methylpyridine-3-carboxamide (HYNIC), tetra 3-hydroxy-N-methyl-2-pyridone chelator abbreviated as Me-3,2-HOPO (4-((4-(3-(bis(2-(3-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamido)ethyl)amino )-2-((bis(2-(3-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamido)ethyl)amino)met hyl)propyl)phenyl)amino)-4-oxobutanoic acid), 1,4,7-triazacyclononane-1-succinic acid-4,7-diacetic acid (NODASA), 1-(1-carboxy-3-carboxypropyl)-4,7-(carboxy)-1,4,7-triazacyclononane (NODAGA), 1,4,7-triazacyclononanetriacetic acid (NOTA), 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (TE2A), 1,4,8,11-tetraazacyclododecane-1,4,8,11-tetraacetic acid (TETA), tris(hydroxypyridone) (THP), terpyridine-bis(methyleneaminetetraacetic acid) (TMT), 1,4,7-triazacyclononane-1,4,7-tris[methylene(2-carboxyethyl)phosphinic acid] (TRAP), 1,4,7,10-tetraazacyclotridecane-N,N',N'',N'''-tetraacetic acid (TRITA), 3-[[4,7-bis[[2-carboxyethyl(hydroxy)phosphoryl]methyl]-1,4,7-triazacyclononan-1-yl]methyl -hydroxy-phosphoryl]propanoic acid, triethylenetetraminehexaacetic acid (TTHA), and N1-(5-aminopentyl)-N1-hydroxy-N4-(5-(N-hydroxy-4-((5-(N-hydroxyacetamido)pentyl)amino)-4-oxobutanamido)pentyl)butanediamide; preferably 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, 1,4,7-triazacyclononanetriacetic acid (NOTA), and N1-(5-aminopentyl)-N1-hydroxy-N4-(5-(N-hydroxy-4-((5-(N-hydroxyacetamido)pentyl)amino)-4-oxobutylamido)pentyl)butanediamide. The selection of radionuclides can depend on the chemical structure and chelating ability of the chelating groups D and D' and the desired application (e.g., diagnosis and therapy). In one embodiment, the radionuclide is selected from any radioactive cation or anion of F, Br, I, Sc, Cu, Ga, Y, In, Lu, Tc, Sm, Sr, Ra, Tb, Ho, Re, Pb, Bi, Ac, Th, Co, Gd, Dy, Zr, At, and Er; preferably, the radionuclide is selected from 18F, 77Br, 131I, 125I, 43Sc, 44Sc, 47Sc, 64Cu, 67Cu, 67Ga, 68Ga, 86Y, 90Y, 90In, 111In, 177Lu, 94Tc, 99Tc, 153Sm, 89Sr, 223Ra, 151Tb, 166Ho, 186Re, 188Re, 212Pb, 213Bi, 212Bi, 225Ac, 227Th, 55Co, 57Co, 152Gd, 153Gd, 157Gd, 166Dy, 89Zr, and 211At, and preferably 68Ga, 64Cu, and 177Lu. In one specific embodiment, the chelating group of the present disclosure is 1,4,7,10-tetraazacyclododecane- N,N',N'',N'''-tetraacetic acid, and the radionuclide is 68Ga. In one specific embodiment, the chelating group of the present disclosure is 1,4,7,10-tetraazacyclododecane- N,N',N'',N'''-tetraacetic acid, and the radionuclide is 64Cu. In one specific embodiment, the chelating group of the present disclosure is 1,4,7,10-tetraazacyclododecane- N,N',N'',N'''-tetraacetic acid, and the radionuclide is 177Lu. In some embodiments, Ld is selected from a chemical bond, -NH-C1-20 alkylene-(CO)-, and -NH-(PEG)i-(CO)-, wherein (PEG)i comprises 1-20 structural units selected from -(O-C2H4)-and -(C2H4-O)-, and is optionally linked to C1-10 alkylene at at least one terminus of the -(O-C2H4)- or -(C2H4-O)- structural unit. In some embodiments, i is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20. In some embodiments, Ld is -NH-(PEG)i-(CO)-, wherein (PEG)i is 1-20 consecutive -(O-C2H4)- or -(C2H4-O)- structural units, and is optionally linked to C1-10 alkylene at at least one terminus of the -(O-C2H4)- or -(C2H4-O)- structural unit; preferably, Ld is -NH-(PEG)i-C1-10 alkylene-(CO)-; more preferably, Ld is -NH-PEG4-C2H4-(CO)-, -NH-PEG3-C2H4-(CO)-, or -NH-PEG4-C3H6-(CO)-; further preferably, Ld is -NH-(C2H4-O)4-C2H4-(CO)-. In some embodiments, Ld is -NH-(PEG)i-C1-10 alkylene-(CO)-, wherein i is an integer selected from 1 to 12; preferably, i is 2, 3, 4, 5, or 6; more preferably, i is 4. In some embodiments, Ld is -NH-PEG4-(CO)-. In some embodiments, L1 and L1' are each independently selected from any one of a chemical bond, C1-10 alkylene, -NH-, and -(CO)-, or any combination thereof; preferably, L1 is selected from -(CH2)4-NH- and -CO-NH-C2H4-NH-, and L1' is selected from a chemical bond, -(CH2)4-NH-, and -CO-NH-C2H4-NH-. In some embodiments, L1 and L1' are identical. In some embodiments, L2 and L2' are each independently selected from any one of a chemical bond, -(CO)-, C1-10 alkylene, and -NH-, or any combination thereof; preferably, L2 is selected from -(CO)- and -(CH2)4-NH-, and L2' is selected from a chemical bond, -(CO)-, and -(CH2)4-NH-. In some embodiments, L2 and L2' are identical. In some embodiments, m is 0. In some embodiments, n is an integer selected from 2 to 10; preferably, n is 2, 3, or 4; more preferably, n is 3. In some embodiments, z is an integer selected from 1 to 10; preferably, z is 1, 2, 3, or 4; more preferably, z is 1. In one specific embodiment, m is 0, n is 3, Ld is -NH-(C2H4-O)4-C2H4-(CO)-, L1 is -(CH2)4-NH-, L2 is -(CO)-, D is 1,4,7,10-tetraazacyclododecane- N,N',N'',N'''-tetraacetic acid, and Q is formula (II') has the following structure: In one specific embodiment, m is 1, n is 3, Ld is -NH-(C2H4-O)4-C2H4-(CO)-, L1 and L1' are - 5 (CH2)4-NH-, L2 and L2' are -(CO)-, D and D' are 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and Q is formula (II') has the following structure: 10 In one specific embodiment, m is 0, n is 3, Ld is -NH-(C2H4-O)4-C2H4-(CO)-, L1 is -CO-NH-C2H4-NH-, L2 is -(CH2)4-NH-, D is 1,4,7,10-tetraazacyclododecane- N,N',N'',N'''-tetraacetic ? XX acid, and Q is . In one specific embodiment, the compound of formula (II') has the following structure: HOOC^ - / ^COOH • 15 In one specific embodiment, m is 0, n is 3, Ld is -NH-(C2H4-O)4-C2H4-(CO)-, L1 is -CO-NH- C2H4-NH-, L2 is -(CH2)4-NH-, D is 1,4,7,10-tetraazacyclododecane- N,N',N'',N'''-tetraacetic . In one specific embodiment, the compound of formula (II') acid, and Q is " has the following structure: COOH HOOC COOH Pharmaceutical Composition Another objective of the present disclosure is to provide a pharmaceutical composition comprising a prophylactically or therapeutically effective amount of the radionuclide conjugate of the present disclosure, and optionally at least one pharmaceutically acceptable carrier. The pharmaceutical composition of the present disclosure may be administered in any manner as long as it achieves the effect of preventing, alleviating, preventing, or treating a symptom in a human or an animal. For example, various suitable dosage forms may be prepared according to the administration route, particularly injections such as a lyophilized powder injection, an injection, or sterile injection powder. The term “pharmaceutically acceptable” means that a substance, when in contact with tissues of the patient within the scope of sound medical judgment, results in no undue toxicity, irritation, allergic reaction, or the like, has a proper advantage-disadvantage ratio, and is effective for the intended use. The term “pharmaceutically acceptable carrier” refers to those carrier materials that are pharmaceutically acceptable and do not interfere with the biological activity and performance of the radionuclide conjugate of the present disclosure. Examples of aqueous carriers include, but are not limited to, buffered saline and the like. Pharmaceutically acceptable carriers also include carrier substances that allow the composition to approximate physiological conditions, such as pH adjusters and buffering agents, and toxicity adjusters, sodium acetate, sodium chloride, potassium chloride, calcium chloride, sodium lactate, and the like. In one embodiment, the nuclide / antibody ratio (DAR) of the pharmaceutical composition of the present disclosure is an integer or non-integer of 0-20, for example about 0 to about 10, about 0 to about 8, about 0 to about 6, about 0 to about 4, about 0 to about 3, about 0 to about 2, or about 0 to about 1. In one particular embodiment, the DAR of the antibody-conjugated drug of the present disclosure is about 0.70, about 0.72, about 0.73, or about 0.83. Treatment Method and Use The radionuclide drug conjugate of the present disclosure can be used for medical treatment and / or diagnosis of related diseases. Related diseases sensitive to treatment with the radionuclide conjugate of the present disclosure include tumors characterized by specific tumor-associated antigens or cell surface receptors, and such tumor cells can be recognized by the targeting moiety in the radionuclide conjugate of the present disclosure and thereby can be killed by the radionuclide in radionuclide conjugate. Therefore, in yet another aspect, the present disclosure further provides use of the radionuclide conjugate of the present disclosure or the pharmaceutical composition of the present disclosure in the manufacture of a therapeutic radiopharmaceutical and / or a diagnostic radiopharmaceutical for diagnosing or treating related diseases. In another aspect, the present disclosure provides the radionuclide conjugate of the present disclosure or the pharmaceutical composition of the present disclosure for use in diagnosing or treating related diseases. In a further aspect, the present disclosure provides a method for diagnosing, delaying, or treating a disease, comprising administering to a subject in need thereof an effective amount of the radionuclide conjugate of the present disclosure or the pharmaceutical composition of the present disclosure. In one embodiment, the disease is an autoimmune disease or a tumor. In some embodiments, the related diseases described herein comprise malignant lymphoma, testicular seminoma, Wilms tumor, neuroblastoma, medulloblastoma, Ewing’s sarcoma, small cell lung cancer, head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, lung squamous cell carcinoma, breast cancer, cervical cancer, skin cancer, gastrointestinal adenocarcinoma, pancreatic cancer, prostate cancer, fibrosarcoma, liposarcoma, and rhabdomyosarcoma. The dose of the antibody-conjugated drug administered to a subject can be adjusted to a considerable extent. The dose may vary depending on the particular administration route and the needs of the subject and may be determined as per the judgment of a healthcare provider. Route of Administration and Kit The conjugate, the radionuclide conjugate, and the pharmaceutical composition according to the present disclosure are administered in an effective amount alone or in combination with an additional therapeutic agent by any common and acceptable means known in the art. The effective amount can vary depending on the severity of the disease, the age and relative health of the subject, the potency of the compound used, and other factors known to those skilled in the art. As a general example, a daily dose of about 0.001 mg / kg body weight to about 100 mg / kg body weight, or particularly about 0.03 mg / kg body weight to 2.5 mg / kg body weight, can be used. In larger mammals, e.g., humans, the daily dose can range from about 0.5 mg to about 2000 mg. As another example, about 5.6 GBq (150 mCi) to about 9.3 GBq (250 mCi) can be used every six weeks, or more specifically, about 7.4 GBq (200 mCi) can be used every six weeks. The becquerel (Bq) is the international unit of radioactivity, representing the intensity of radioactivity of one atomic nucleus decaying per second. The curie (Ci) is the original unit of radioactivity; 1 curie (Ci) = 3.7 X 1010 becquerel (Bq).The conjugate, the radionuclide conjugate, and the pharmaceutical composition of the present disclosure are generally administered in the form of a pharmaceutical composition comprising an active pharmaceutical ingredient and various other pharmaceutically acceptable components, see, e.g., Remington’s Pharmaceutical Science (15th ed., Mack Publishing Company, Easton, Pa., 1980). The preferred or desired form depends on the intended mode of administration and therapeutic use. Depending on the desired formulation, the composition can further comprise a pharmaceutically acceptable non-toxic carrier or diluent, which is defined as a carrier commonly used in the preparation of pharmaceutical compositions for administration to animals or humans. The choice of diluent does not affect the biological activity of the combination. Examples of diluents include, but are not limited to, distilled water, physiological phosphate-buffered saline, Ringer’s solution, glucose solution, and Hank’s solution. In addition, the pharmaceutical composition or formulation can further comprise other carriers, adjuvants, or non-toxic, non-therapeutic, non-immunogenic stabilizers, and the like. The conjugate, the radionuclide conjugate, and the pharmaceutical composition of the present disclosure can be administered in the form of a pharmaceutical composition by any conventional route, e.g., enterally, e.g., orally, e.g., in the form of a tablet or capsule; parenterally, e.g., in the form of an injectable solution or suspension; or topically, e.g., ocularly or nasally, e.g., in the form of an emulsion, gel, ointment, cream, or suppository. In one embodiment, the pharmaceutical composition is a solution of the active ingredient, including a suspension or dispersion, such as an isotonic aqueous solution. In the case of lyophilized compositions comprising the active ingredient alone or together with a carrier (e.g., mannitol), dispersions or suspensions can be prepared before use. Non-limiting examples of the carrier include fillers, e.g., sugars, e.g., lactose, sucrose, mannitol, or sorbitol; cellulose formulations and / or calcium phosphates, e.g., tricalcium phosphate or calcium hydrogen phosphate; binders, e.g., starches, e.g., corn, wheat, rice, or potato starch, methylcellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, and / or polyvinylpyrrolidone; and / or, if desired, disintegrants, e.g., the starches described above, carboxymethyl starch, cross-linked polyvinylpyrrolidones, or alginic acid or a salt thereof, e.g., sodium alginate. Other carriers include, but are not limited to, rheology modifiers and lubricants, e.g., silicic acid, talc, stearic acid or a salt thereof (e.g., magnesium stearate or calcium stearate), and / or polyethylene glycol or a derivative thereof. The present disclosure further provides a pharmaceutical combination, e.g., a kit, comprising a) a first agent, which is the radionuclide conjugate or a pharmaceutically acceptable salt thereof according to the present disclosure, and b) instructions for administration. Beneficial Effects The present disclosure provides a new radionuclide conjugate. By means of ligase-catalyzed site-specific conjugation, an albumin-binding unit and a chelating group can be site-specifically conjugated in one step to an engineered targeting moiety (such as Fab, scFv, nanobody, and sdAb), to obtain the corresponding conjugate. The conjugate of the present disclosure has a uniform and stable structure. While retaining the antigen-binding capacity of the original targeting moiety, it exhibits excellent in vitro stability. Meanwhile, the conjugation process is simple and easy to scale up. Compared with the prior art, the radionuclide conjugate of the present disclosure possesses an appropriate blood circulation half-life, achieves higher tumor enrichment and longer tumor retention time, and shows higher tumor-inhibitory activity. The radionuclide conjugate of the present disclosure features a stable structure and a low nuclide off-target rate, which greatly reduces toxic and side effects. In particular, a desired therapeutic effect can be achieved using only an appropriate amount of the radionuclide, allowing a patient to be exposed to a lower total absorbed radiation dose. In another aspect, manufacturing cost is reduced while lessening the environmental burden. Examples The solutions of the present disclosure are further described in detail below with reference to specific examples. It will be appreciated that the following examples are merely examples for clearly illustrating the technical solutions of the present disclosure, and are not intended to limit the present disclosure. For those of ordinary skill in the art, other different forms of variations or modifications can be made based on the description of the present disclosure, and it is unnecessary and impossible to exhaustively list all the embodiments herein. The obvious variations or modifications introduced thereby still fall within the scope of the present disclosure. Unless otherwise indicated, devices, reagents, and materials used herein are commercially available. Example 1: Synthesis of Compound LP0 HN 0 LPOa LPOb LPOc LPO 1.1 Synthesis of intermediate compound LP0a BocHN BocHN LPOa 1. 30% HFIPDCM 2. Purification Step 4 Step 1 Fmoc-Lys(Dde)-OH / DIEA / DMF I 0. ----------------------* F mocHN Step 2 1.20% Piperidine \D MF 2. Boc-Gly-Gly-Gly-OH / DIC / Oxyma / DMF Step 3 1.20% Piperidine'DMF 2.Fmoc-PEG4-CH2CH2COOH®IC / OxymaT>MF Step 1: Resin swelling and condensation 2-CTC-Resin (CAS No.: 42074-68-0, 1.9 g, 2.0 mmol) was weighed into a solid-phase synthesis tube, and dichloromethane (20 mL) was added. The mixture was stirred, mixed well, subjected to swelling for 30 min, and filtered under vacuum. Fmoc-Lys(Dde)-OH (CAS No.: 150629-67-7, 3.2 g) was weighed into an erlenmeyer flask, and dichloromethane (20 mL) was added. The mixture was shaken until complete dissolution. Subsequently, diisopropylethylamine (0.78 g) was added to the erlenmeyer flask, and the mixture was mixed well. The solution in the erlenmeyer flask was added to the solid-phase synthesis tube described above, and the mixture was stirred and mixed well. The mixture was bubbled with nitrogen from the bottom of the solid-phase synthesis tube for about 2 h. A mixed solution of methanol / diisopropylethylamine (6 mL, v / v = 5:1) was added to the system for capping for 30 min. Subsequently, the reaction system was filtered under vacuum, washed once with dichloromethane (20 mL), and washed three times with N,N'-dimethylformamide (20 mL for each washing). Step 2: Deprotection and condensation An Fmoc-deprotection reagent solution (N,N'-dimethylformamide / piperidine = 4:1, containing 1% 1-hydroxybenzotriazole HOBt, 20 mL) was added to the solid-phase synthesis tube in the previous step. The mixture was stirred for 10 min, and then the reaction system was completely filtered under vacuum. Then the same Fmoc-deprotection reagent solution (20 mL) was added, and the mixture was stirred for 10 min. The reaction system was completely filtered under vacuum. Subsequently, the resin was washed four times with N,N'-dimethylformamide (20 mL for each washing). The resin was tested with ninhydrin and exhibited a dark blue color. Fmoc-PEG4-CH2CH2COOH (CAS No.: 557756-85-1, 2.9 g) and Oxyma (CAS No.: 57361-81- 6, 0.8 g) were weighed into an erlenmeyer flask. N,N'-Dimethylformamide (20 mL) was added, and then the mixture was shaken until complete dissolution. N,N'-Diisopropylcarbodiimide (DIC, 0.75 g) was then added to the erlenmeyer flask. The mixture was mixed well and placed at 0-10 °C for activation for 3-5 min. Subsequently, the solution in the erlenmeyer flask was added to the solid-phase synthesis tube described above, and the mixture was stirred and mixed well. Then, the mixture was bubbled with nitrogen from the bottom of the solid-phase synthesis tube for about 2 h. The resin was tested using ninhydrin until it was substantially colorless. The solvent in the reaction system was removed under vacuum, and the mixture was washed three times with N,N'-dimethylformamide (20 mL for each washing). Step 3: Deprotection and condensation An Fmoc-deprotection reagent solution (N,N'-dimethylformamide / piperidine = 4:1, containing 1% HOBt, 20 mL) was added to the solid-phase synthesis tube in the previous step. The mixture was stirred for 10 min, and then the reaction system was completely filtered under vacuum. Then the same Fmoc-deprotection reagent solution (20 mL) was added, and the mixture was stirred for 10 min. The reaction system was completely filtered under vacuum. Subsequently, the resin was washed four times with N,N'-dimethylformamide (20 mL for each washing). The resin was tested with ninhydrin and exhibited a dark blue color. Boc-Gly-Gly-Gly-OH (CAS No.: 28320-73-2, 1.7 g) and Oxyma (CAS No.: 57361-81-6, 0.8 g) were weighed into an erlenmeyer flask. N,N'-Dimethylformamide (20 mL) was added, and then the mixture was shaken until complete dissolution. DIC (0.75 g) was then added to the erlenmeyer flask. The mixture was mixed well and placed at 0-10 °C for activation for 3-5 min. Subsequently, the solution in the erlenmeyer flask was added to the solid-phase synthesis tube described above, and the mixture was stirred and mixed well. Then, the mixture was bubbled with nitrogen from the bottom of the solid-phase synthesis tube for about 2 h. The resin was tested using ninhydrin until it was substantially colorless. The solvent in the reaction system was removed under vacuum, and the mixture was washed twice with N,N'-dimethylformamide (20 mL for each washing) and further washed three times with dichloromethane (20 mL for each washing). The solvent in the reaction system was removed under vacuum, and then the resin was air-dried to a free-flowing state. Step 4: Cleavage and purification Dichloromethane (28 mL) and hexafluoroisopropanol (12 mL) were added to a round-bottom flask, and the mixture was mixed well. The resin obtained in the previous step was added to the solution described above. The mixture was stirred for about 2 h. The reaction system was filtered, and the resin was washed with a small amount of dichloromethane. The resulting filtrate was completely concentrated under reduced pressure and purified by preparative reversed-phase high-performance liquid chromatography (RP-HPLC). The resulting preparation product was lyophilized to give pure LP0a (1.4 g, yield: 85%). LC-MS analysis showed [M+H]+ = 829.44. 1.2 Synthesis of intermediate compound LP0b (E)-4-Amino-6-(((4'-amino-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid (EB-NH2, 0.3 g, 1.0 eq.) and LP0a (1.37 g, 3.0 eq.) were weighed into a round-bottom flask. N,N'-Dimethylformamide (12 mL) was added, and the mixture was stirred until complete dissolution. Subsequently, O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU, 0.84 g, 4.0 eq.) and diisopropylethylamine (548 pL, 6.0 eq.) were added to the system. The reaction system was stirred at room temperature overnight, and EB-NH2 was monitored by high-performance liquid chromatography (HPLC) until the reaction was substantially completed. The mixture was purified by preparative reversed-phase high-performance liquid chromatography. The resulting preparation product was lyophilized to give pure LP0b (0.36 g, yield: 49%). LC-MS analysis showed [M+H]+ = 1352.55. 1.3 Synthesis of intermediate compound LP0c Step 1: Deprotection Compound LP0b (0.36 g) was weighed into a round-bottom flask, and purified water (8 mL) was added. The mixture was stirred and mixed well. Then, hydrazine hydrate (0.4 mL) was added to the system. The reaction system was stirred at room temperature for 1 h, and the reaction was monitored by HPLC until the reaction was substantially completed. The mixture was purified by preparative reversed-phase high-performance liquid chromatography. The resulting preparation product was lyophilized to give pure LP0b-1 (0.15 g, yield: 47%). LC-MS analysis showed [M+H]+ = 1189.6. Step 2: Condensation Compound LP0b-1 (0.15 g, 1.0 eq.) and tri-tert-butyl 1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetate (DOTA-(COOtBu)3, 80 mg, 1.1 eq.) were weighed into a round-bottom flask. N,N'-Dimethylformamide (6 mL) was added, and the mixture was stirred until complete dissolution. Subsequently, HATU (72 mg, 1.5 eq.) and diisopropylethylamine (63 pL, 3.0 eq.) were added to the system. The reaction system was stirred at room temperature overnight, and the reaction was monitored by HPLC until the reaction was substantially completed. The mixture was purified by preparative reversed-phase high-performance liquid chromatography. The resulting preparation product was lyophilized to give pure LP0c (0.125 g, yield: 60%). LC-MS analysis showed [1 / 2M+H]+ = 872.89. 1.4 Synthesis of compound LP0 Compound LP0c (0.12 g) was weighed into a round-bottom flask, and a mixed solution of purified water / trifluoroacetic acid (2 mL, v / v = 5:95) was added. The mixture was stirred and mixed well. The mixture was reacted at room temperature for 2 h, and the reaction was monitored by HPLC until the reaction was substantially completed. The mixture was purified by preparative reversed-phase high-performance liquid chromatography. The resulting preparation product was lyophilized to give pure LP0 (74 mg, yield: 73%). LC-MS analysis showed [M+H]+ = 1476.4. Example 2: Synthesis of Compound LP1 2.1 Synthesis of intermediate compound LP1a Step 1 : Resin swelling and condensation 2-CTC-Resin (CAS No.: 42074-68-0, 1.9 g, 2.0 mmol) was weighed into a solid-phase synthesis tube, and dichloromethane (20 mL) was added. The mixture was stirred, mixed well, subjected to swelling for 30 min, and filtered under vacuum. Fmoc-Lys(Dde)-OH (CAS No.: 150629-67-7, 3.2 g) was weighed into an erlenmeyer flask, and dichloromethane (20 mL) was added. The mixture was shaken until complete dissolution. Subsequently, diisopropylethylamine (0.78 g) was added to the erlenmeyer flask, and the mixture was mixed well. The solution in the erlenmeyer flask was added to the solid-phase synthesis tube described above, and the mixture was stirred and mixed well. The mixture was bubbled with nitrogen from the bottom of the solid-phase synthesis tube for about 2 h. A mixed solution of methanol / diisopropylethylamine (6 mL, v / v = 5:1) was added to the system for capping for 30 min. Subsequently, the reaction system was filtered under vacuum, washed once with dichloromethane (20 mL), and washed three times with N,N'-dimethylformamide (20 mL for each washing). Step 2: Deprotection and condensation An Fmoc-deprotection reagent solution (N,N'-dimethylformamide / piperidine = 4:1, containing 1% HOBt, 20 mL) was added to the solid-phase synthesis tube in the previous step. The mixture was stirred for 10 min, and then the reaction system was completely filtered under vacuum. Then the same Fmoc-deprotection reagent solution (20 mL) was added, and the mixture was stirred for 10 min. The reaction system was completely filtered under vacuum. Subsequently, the resin was washed four times with N,N'-dimethylformamide (20 mL for each washing). The resin was tested with ninhydrin and exhibited a dark blue color. p-Methylphenylbutyric acid (1.07 g) and Oxyma (0.8 g) were weighed into an erlenmeyer flask. N,N'-Dimethylformamide (20 mL) was added, and then the mixture was shaken until complete dissolution.DIC (0.75 g) was then added to the erlenmeyer flask. The mixture was mixed well and placed at 0-10 °C for activation for 3-5 min. Subsequently, the solution in the erlenmeyer flask was added to the solid-phase synthesis tube described above, and the mixture was stirred and mixed well. Then, the mixture was bubbled with nitrogen from the bottom of the solidphase synthesis tube for about 2 h. The resin was tested using ninhydrin until it was substantially colorless. The solvent in the reaction system was removed under vacuum, and the mixture was washed three times with N,N'-dimethylformamide (20 mL for each washing). Step 3: Deprotection and condensation A Dde-deprotection reagent solution (N,N'-dimethylformamide / hydrazine hydrate = 95:5, 20 mL) was added to the solid-phase synthesis tube in the previous step. The mixture was stirred for 10 min, and then the reaction system was completely filtered under vacuum. Then the same Dde-deprotection reagent solution (20 mL) was added, and the mixture was stirred for 10 min. The reaction system was completely filtered under vacuum. Subsequently, the resin was washed four times with N,N'-dimethylformamide (20 mL for each washing). The resin was tested with ninhydrin and exhibited a dark blue color. Fmoc-PEG4-CH2CH2COOH (2.9 g) and Oxyma (0.8 g) were weighed into an erlenmeyer flask. N,N'-Dimethylformamide (20 mL) was added, and then the mixture was shaken until complete dissolution. DIC (0.75 g) was then added to the erlenmeyer flask. The mixture was mixed well and placed at 0-10 °C for activation for 3-5 min. Subsequently, the solution in the erlenmeyer flask was added to the solid-phase synthesis tube described above, and the mixture was stirred and mixed well. Then, the mixture was bubbled with nitrogen from the bottom of the solidphase synthesis tube for about 2 h. The resin was tested using ninhydrin until it was substantially colorless. The solvent in the reaction system was removed under vacuum, and the mixture was washed three times with N,N'-dimethylformamide (20 mL for each washing). Step 4: Deprotection and condensation An Fmoc-deprotection reagent solution (N,N'-dimethylformamide / piperidine = 4:1, containing 1% HOBt, 20 mL) was added to the solid-phase synthesis tube in the previous step. The mixture was stirred for 10 min, and then the reaction system was completely filtered under vacuum. Then the same Fmoc-deprotection reagent solution (20 mL) was added, and the mixture was stirred for 10 min. The reaction system was completely filtered under vacuum. Subsequently, the resin was washed four times with N,N'-dimethylformamide (20 mL for each washing). The resin was tested with ninhydrin and exhibited a dark blue color. Boc-Gly-Gly-Gly-OH (1.7 g) and Oxyma (0.8 g) were weighed into an erlenmeyer flask. N,N'-Dimethylformamide (20 mL) was added, and then the mixture was shaken until complete dissolution. DIC (0.75 g) was then added to the erlenmeyer flask. The mixture was mixed well and placed at 0-10 °C for activation for 3-5 min. Subsequently, the solution in the erlenmeyer flask was added to the solid-phase synthesis tube described above, and the mixture was stirred and mixed well. Then, the mixture was bubbled with nitrogen from the bottom of the solidphase synthesis tube for about 2 h. The resin was tested using ninhydrin until it was substantially colorless. The solvent in the reaction system was removed under vacuum, and the mixture was washed twice with N,N'-dimethylformamide (20 mL for each washing) and further washed three times with dichloromethane (20 mL for each washing). The solvent in the reaction system was removed under vacuum, and then the resin was air-dried to a free-flowing state. Step 5: Cleavage and purification Dichloromethane (28 mL) and hexafluoroisopropanol (12 mL) were added to a round-bottom flask, and the mixture was mixed well. The resin obtained in the previous step was added to the solution described above. The mixture was stirred for about 2 h. The reaction system was filtered, and the resin was washed with a small amount of dichloromethane. The resulting filtrate was completely concentrated under reduced pressure and purified by preparative reversed-phase high-performance liquid chromatography. The resulting preparation product was lyophilized to give pure LP1a (1.3 g, yield: 79%). LC-MS analysis showed [M+H]+ = 825.37. 2.2 Synthesis of intermediate compound LP1b LP1a LP1b LP1a (0.78 g, 1.0 eq.) and Fmoc-ethylenediamine hydrochloride (0.3 g, 1.0 eq.) were weighed into a round-bottom flask. N,N'-Dimethylformamide (10 mL) was added, and the mixture was stirred until complete dissolution. Diisopropylethylamine (620 p,L, 4.0 eq.) was then added. Subsequently, HATU (0.54 g, 1.5 eq.) was added to the system, and the reaction system was stirred at room temperature for about 2 h. The reaction was monitored by HPLC until the reaction was substantially completed. The mixture was purified by preparative reversed-phase high-performance liquid chromatography. The resulting preparation product was lyophilized to give pure LP1b (0.94 g, yield: 92%). LC-MS analysis showed [M+H]+ = 1089.53. 2.3 Synthesis of intermediate compound LP1c LPIb Compound LP1b was weighed into a round-bottom flask (0.5 g, 1.0 eq.). N,N'- Dimethylformamide (5 mL) was added, and the mixture was stirred until complete dissolution. Subsequently, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 35 pL, 0.5 eq.) was added to the system, and the mixture was placed at room temperature and stirred for 1.5 h. The reaction was monitored by HPLC until the reaction was substantially completed. Then, DOTA-(COOtBu)3 (0.26 g, 1.0 eq.) and HATU (0.26 g, 1.5 eq.) were added to the system, and the mixture was stirred for dissolution. Diisopropylethylamine (305 uL, 4.0 eq.) was then added to the system, and the reaction system was stirred at room temperature overnight. The reaction was monitored by HPLC until the reaction was substantially completed. The mixture was purified by preparative reversed-phase high-performance liquid chromatography. The resulting preparation product was lyophilized to give pure LP1c (0.33 g, yield: 51%). LC-MS analysis showed [M+H]+ = 1421.77. 2.4 Synthesis of compound LP1 Compound LP1c (0.23 g) was weighed into a round-bottom flask, and a mixed solution of purified water / trifluoroacetic acid (2.5 mL, v / v = 5:95) was added. The mixture was stirred and mixed well. The mixture was reacted at room temperature for 3 h, and the reaction was monitored by HPLC until the reaction was substantially completed. The mixture was purified by preparative reversed-phase high-performance liquid chromatography. The resulting preparation product was lyophilized to give pure LP1 (115 mg, yield: 62%). LC-MS analysis showed [M+H]+ = 1153.6. Example 3: Synthesis of Compound LP2 HOOC—1 \! '—cool I Referring to the synthetic method for compound LP1 in Example 2, compound LP2 was prepared by replacing p-methylphenylbutyric acid with 4-(4-iodophenyl)butyric acid to finally give pure compound LP2 (150 mg). LC-MS analysis showed [M+H]+ = 1265.44. Example 4: Synthesis of Compound LP3 (Control) Referring to the synthetic method for compound LP1 in Example 2, compound LP3 was prepared by replacing p-methylphenylbutyric acid with acetic acid to finally give pure compound LP3 (140 mg). LC-MS analysis showed [M+H]+ = 1035.51. 5 Example 5: Synthesis of Compound LP4 10 15 (1) Resin swelling and ethylenediamine coupling: 2-CTC-Resin (450 mg) was weighed into a solid-phase synthesis tube, and dichloromethane (6 mL) was added. The mixture was stirred, mixed well, and subjected to swelling for 30 min. The solvent was removed under vacuum. Ethylenediamine (107 pL) was measured into an EP tube, and dichloromethane (6 mL) was added. The mixture was shaken until complete dissolution. Subsequently, diisopropylethylamine (600 pL) was added to the erlenmeyer flask, and the mixture was mixed well. The solution described above was added to the solid-phase synthesis tube described above, and the mixture was stirred and mixed well. Then, the mixture was bubbled with nitrogen from the bottom of the solid-phase synthesis tube for about 2 h. A mixed solution of methanol / diisopropylethylamine (3 mL, v / v = 5:1) was added to the system for capping for 30 min. Subsequently, the mixture was filtered under vacuum, and the mixture was washed once with dichloromethane (10 mL) and washed three times with N,N'-dimethylformamide (10 mL for each washing). (2) Coupling of Fmoc-Lys(Dde)-OH: Fmoc-Lys(Dde)-OH (920 mg), HATU (576 mg), and HOAT (208 mg) were weighed into a PE tube, DMF (12 mL) was added, and the mixture was mixed well until complete dissolution. Finally, diisopropylethylamine (600 pL) was added, and the mixture was shaken sufficiently and mixed well. The solution described above was added to the synthesis tube. Then, the mixture was bubbled with nitrogen from the bottom of the solid-phase synthesis tube for about 2 h. The resin was tested using ninhydrin until it was substantially colorless. The solvent was removed under vacuum, and the mixture was washed three times with N,N'-dimethylformamide (10 mL for each washing). (3) Deprotection and coupling of Fmoc-PEG4-OH An Fmoc-deprotection reagent solution (N,N'-dimethylformamide / piperidine = 4:1, containing 1% HOBt, 10 mL) was added to the solid-phase synthesis tube in the previous step. The mixture was stirred for 10 min and completely filtered under vacuum. Then the same Fmoc-deprotection reagent solution (10 mL) was added, and the mixture was stirred for 10 min and completely filtered under vacuum. Subsequently, the mixture was washed four times with N,N'-dimethylformamide (10 mL for each washing). The resin was tested with ninhydrin and exhibited a dark blue color. Fmoc-PEG4-OH (585 mg), HATU (576 mg), and HOAT (208 mg) were weighed into a PE tube, DMF (12 mL) was added, and the mixture was mixed well until complete dissolution. Finally, diisopropylethylamine (600 pL) was added, and the mixture was shaken sufficiently and mixed well. The solution described above was added to the synthesis tube. Then, the mixture was bubbled with nitrogen from the bottom of the solid-phase synthesis tube for about 2 h. The resin was tested using ninhydrin until it was substantially colorless. The solvent was removed under vacuum, and the mixture was washed three times with N,N'-dimethylformamide (10 mL for each washing). (4) Deprotection and coupling of Fmoc-Gly-Gly-OH An Fmoc-deprotection reagent solution (N,N'-dimethylformamide / piperidine = 4:1, containing 1% HOBt, 10 mL) was added to the solid-phase synthesis tube in the previous step. The mixture was stirred for 10 min and completely filtered under vacuum. Then the same Fmoc-deprotection reagent solution (10 mL) was added, and the mixture was stirred for 10 min and completely filtered under vacuum. Subsequently, the mixture was washed four times with N,N'-dimethylformamide (10 mL for each washing). The resin was tested with ninhydrin and exhibited a dark blue color. Fmoc-Gly-Gly-OH (567 mg), HATU (576 mg), and HOAT (208 mg) were weighed into a PE tube, DMF (12 mL) was added, and the mixture was mixed well until complete dissolution. Finally, diisopropylethylamine (600 pL) was added, and the mixture was shaken sufficiently and mixed well. The solution described above was added to the synthesis tube. Then, the mixture was bubbled with nitrogen from the bottom of the solid-phase synthesis tube for about 2 h. The resin was tested using ninhydrin until it was substantially colorless. The solvent was removed under vacuum, and the mixture was washed three times with N,N'-dimethylformamide (10 mL for each washing). (5) Deprotection and condensation of Boc-Gly-OH An Fmoc-deprotection reagent solution (N,N'-dimethylformamide / piperidine = 4:1, containing 1% HOBt, 10 mL) was added to the solid-phase synthesis tube in the previous step. The mixture was stirred for 10 min and completely filtered under vacuum. Then the same Fmoc-deprotection reagent solution (10 mL) was added, and the mixture was stirred for 10 min and completely filtered under vacuum. Subsequently, the mixture was washed four times with N,N'-dimethylformamide (10 mL for each washing). The resin was tested with ninhydrin and exhibited a dark blue color. Boc-Gly-OH (280 mg), HATU (576 mg), and HOAT (208 mg) were weighed into a PE tube, DMF (12 mL) was added, and the mixture was mixed well until complete dissolution. Finally, diisopropylethylamine (600 pL) was added, and the mixture was shaken sufficiently and mixed well. The solution described above was added to the synthesis tube. Then, the mixture was bubbled with nitrogen from the bottom of the solid-phase synthesis tube for about 2 h. The resin was tested using ninhydrin until it was substantially colorless. The solvent was removed under vacuum, and the mixture was washed three times with N,N'-dimethylformamide (10 mL for each washing). (6) Deprotection and coupling of ibuprofen A Dde-deprotection reagent solution (N,N'-dimethylformamide / hydrazine hydrate = 95:5, 10 mL) was added to the solid-phase synthesis tube in the previous step. The mixture was stirred for 10 min. Then, the mixture was completely filtered under vacuum. The same Dde-deprotection reagent solution (10 mL) was added, and the mixture was stirred for 10 min and completely filtered under vacuum. Subsequently, the mixture was washed four times with N,N'-dimethylformamide (10 mL for each washing). The resin was tested with ninhydrin and exhibited a dark blue color. Ibuprofen (330 mg) and Oxyma (432 mg) were weighed into a PE tube, N,N'-dimethylformamide (6 mL) was added, and the mixture was mixed well until complete dissolution. Finally, DIC (300 pL) was added, and the mixture was shaken sufficiently and mixed well. The solution described above was added to the synthesis tube. Then, the mixture was bubbled with nitrogen from the bottom of the solid-phase synthesis tube for about 2 h. The resin was tested using ninhydrin until it was substantially colorless. The solvent was removed under vacuum, and the mixture was washed twice with N,N'-dimethylformamide (10 mL for each washing) and washed three times with dichloromethane (10 mL for each washing). The solvent was removed under vacuum, and then the resin was air-dried to a free-flowing state. (7) Cleavage Dichloromethane (7 mL) and hexafluoroisopropanol (3 mL) were added to a round-bottom flask, and the mixture was mixed well. The resin obtained in the previous step was added to the solution described above. The mixture was stirred for about 2 h. The mixture was filtered, and the resin was washed with a small amount of dichloromethane. The resulting filtrate was completely concentrated under reduced pressure to give an oily crude peptide, which was weighed. (8) Coupling of DOTA DOTA (916 mg) and HOBt (212 mg) were weighed into a PE tube, N,N'-dimethylformamide (1 mL) was added, and the mixture was mixed well until complete dissolution. The solution described above was added to a 50 mL round-bottom flask containing the crude peptide, and dichloromethane (5 mL) was added. The mixture was shaken well, and DIC (300 uL) was slowly added dropwise. The mixture was stirred overnight. The solution was concentrated to dryness by a rotary evaporator to give a pure product. (9) Deprotection and purification Preparation of 10 mL of a conventional cleavage solution: phenol (500 mg), Tips (1 mL), and purified water (0.5 mL), with the volume brought to 10 mL by using TFA. The deprotection solution described above was poured into the pure product obtained in (8), and the mixture was stirred for 2 h. Cold ethyl ether (20 mL) was added, and sufficient precipitation was achieved. The mixture was then centrifuged at 3500 rpm for 3 min using a centrifuge. After the centrifugation was completed, the supernatant was discarded, and the mixture was centrifuged three times. The mixture was air-dried at room temperature. The resulting pure product was separated by semi-preparative liquid chromatography and lyophilized to give compound LP4 (20 mg, purity: 99.74%, overall yield: 11%). LC-MS analysis showed [M+H]+ = 1182.4, and the value is consistent with the theoretical value. Example 6: Synthesis of Compound LP5 H2N^NH2 ci —Q --------* m2n ' 'NH2 ------------ Referring to the synthetic method for compound LP4 in Example 5, compound LP5 was synthesized according to the route shown above. LC-MS analysis showed [M+H]+ = 1277.35, and the value is consistent with the theoretical value. Example 7: Synthesis of Compound LP6 NHDde BocHN’ DOTA^h, Fmoc-Lys(Dde)-OH -------------*■ FmocHW Referring to the synthetic method for compound LP4 in Example 5, compound LP6 was synthesized according to the route shown above. LC-MS analysis showed [M+H]+ = 1120.25, and the value is consistent with the theoretical value. Example 8: Synthesis of Compound LP7 Referring to the synthetic method for compound LP4 in Example 5, compound LP7 was synthesized according to the route shown above. LC-MS analysis showed [1 / 2M+H]+ = 630.6, and the value is consistent with the theoretical value. 10 Example 9: Synthesis of Compound LP8 NHDde z-v 1.20% Piperidine.'DMF 2. Ftnoc-Gly-Gly-OH _ NH J 1.20%Piperidine.DMF + = fmccl^WOH I h rpFmoc-PEa-CH.CH.COOH . HN- -----W---—--» F 1.20% Piperidine.'DMF 2 Boc-Giy-OH 1 . DOT^ufe xx^Nn. -------„ H 20% HFIP / DCM ---------------------------. b^n^A-Y11' 1.2% Hydra zine hydrate. DMF ^^^2.4-(4-Iodo-3-methylphenyI)butanoic acid Referring to the synthetic method for compound LP4 in Example 5, compound LP8 was synthesized according to the route shown above. LC-MS analysis showed [M+H]+ = 1279.85, and the value is consistent with the theoretical value. Example 10: Synthesis of Compound LP9 NHDde NHDde FmocHN BocHN. ' FmocHN' NHDde __ 1.2 0 % Piperidine.'DMF 2.Boc-Gh-OH______ 20% HFIP / DCM 1.20% Piperidtne.'DMF 2.Fmoc-ACP-OH 1.20%Piperidine.DMF 2. Ftnoc-Giy-Giy-OH NHDde BocHN. BocHN. DOTA(fBu)3 ■COOH LP9 Referring to the synthetic method for compound LP4 in Example 5, compound LP9 was synthesized according to the route shown above. LC-MS analysis showed [M+H]+ = 1131.45, and the value is consistent with the theoretical value. Example 11: Synthesis of Compound LP10 5 Referring to the synthetic method for compound LP4 in Example 5, compound LP10 was synthesized according to the route shown above. LC-MS analysis showed [1 / 2M+H]+ = 676.70, and the value is consistent with the theoretical value. Example 12: Synthesis of Compound LP11 (1) Resin swelling and ethylenediamine coupling: 2-CTC-Resin (450 mg) was weighed into a solid-phase synthesis tube, and dichloromethane (6 mL) was added. The mixture was stirred, mixed well, and subjected to swelling for 30 min. The solvent was removed under vacuum. Ethylenediamine (107 pL) was measured into an EP tube, and dichloromethane (6 mL) was added. The mixture was shaken until complete dissolution. Subsequently, diisopropylethylamine (600 pL) was added to the erlenmeyer flask, and the mixture was mixed well. The solution described above was added to the solid-phase synthesis tube described above, and the mixture was stirred and mixed well. Then, the mixture was bubbled with nitrogen from the bottom of the solid-phase synthesis tube for about 2 h. A mixed solution of methanol / diisopropylethylamine (3 mL, v / v = 5:1) was added to the system for capping for 30 min. Subsequently, the mixture was filtered under vacuum, and the mixture was washed once with dichloromethane (10 mL) and washed three times with N,N'-dimethylformamide (10 mL for each washing). (2) Coupling of Fmoc-Lys(Dde)-OH: Fmoc-Lys(Dde)-OH (920 mg), HATU (576 mg), and HOAT (208 mg) were weighed into a PE tube, DMF (12 mL) was added, and the mixture was mixed well until complete dissolution. Finally, diisopropylethylamine (600 pL) was added, and the mixture was shaken sufficiently and mixed well. The solution described above was added to the synthesis tube. Then, the mixture was bubbled with nitrogen from the bottom of the solid-phase synthesis tube for about 2 h. The resin was tested using ninhydrin until it was substantially colorless. The solvent was removed under vacuum, and the mixture was washed three times with N,N'-dimethylformamide (10 mL for each washing). (3) Deprotection and coupling of Fmoc-PEG4-OH An Fmoc-deprotection reagent solution (N,N'-dimethylformamide / piperidine = 4:1, containing 1% HOBt, 10 mL) was added to the solid-phase synthesis tube in the previous step. The mixture was stirred for 10 min and completely filtered under vacuum. Then the same Fmoc-deprotection reagent solution (10 mL) was added, and the mixture was stirred for 10 min and completely filtered under vacuum. Subsequently, the mixture was washed four times with N,N'-dimethylformamide (10 mL for each washing). The resin was tested with ninhydrin and exhibited a dark blue color. Fmoc-PEG4-OH (585 mg), HATU (576 mg), and HOAT (208 mg) were weighed into a PE tube, DMF (12 mL) was added, and the mixture was mixed well until complete dissolution. Finally, diisopropylethylamine (600 uL) was added, and the mixture was shaken sufficiently and mixed well. The solution described above was added to the synthesis tube. Then, the mixture was bubbled with nitrogen from the bottom of the solid-phase synthesis tube for about 2 h. The resin was tested using ninhydrin until it was substantially colorless. The solvent was removed under vacuum, and the mixture was washed three times with N,N'-dimethylformamide (10 mL for each washing). (4) Deprotection and coupling of Fmoc-Lys(Dde)-OH An Fmoc-deprotection reagent solution (N,N'-dimethylformamide / piperidine = 4:1, containing 1% HOBt, 10 mL) was added to the solid-phase synthesis tube in the previous step. The mixture was stirred for 10 min and completely filtered under vacuum. Then the same Fmoc-deprotection reagent solution (10 mL) was added, and the mixture was stirred for 10 min and completely filtered under vacuum. Subsequently, the mixture was washed four times with N,N'-dimethylformamide (10 mL for each washing). The resin was tested with ninhydrin and exhibited a dark blue color. Fmoc-Lys(Dde)-OH (920 mg), HATU (576 mg), and HOAT (208 mg) were weighed into a PE tube, DMF (12 mL) was added, and the mixture was mixed well until complete dissolution. Finally, diisopropylethylamine (600 uL) was added, and the mixture was shaken sufficiently and mixed well. The solution described above was added to the synthesis tube. Then, the mixture was bubbled with nitrogen from the bottom of the solid-phase synthesis tube for about 2 h. The resin was tested using ninhydrin until it was substantially colorless. The solvent was removed under vacuum, and the mixture was washed three times with N,N'-dimethylformamide (10 mL for each washing). (5) Deprotection and coupling of Fmoc-PEG4-OH An Fmoc-deprotection reagent solution (N,N'-dimethylformamide / piperidine = 4:1, containing 1% HOBt, 10 mL) was added to the solid-phase synthesis tube in the previous step. The mixture was stirred for 10 min and completely filtered under vacuum. Then the same Fmoc-deprotection reagent solution (10 mL) was added, and the mixture was stirred for 10 min and completely filtered under vacuum. Subsequently, the mixture was washed four times with N,N'-dimethylformamide (10 mL for each washing). The resin was tested with ninhydrin and exhibited a dark blue color. Fmoc-PEG4-OH (585 mg), HATU (576 mg), and HOAT (208 mg) were weighed into a PE tube, DMF (12 mL) was added, and the mixture was mixed well until complete dissolution. Finally, diisopropylethylamine (600 pL) was added, and the mixture was shaken sufficiently and mixed well. The solution described above was added to the synthesis tube. Then, the mixture was bubbled with nitrogen from the bottom of the solid-phase synthesis tube for about 2 h. The resin was tested using ninhydrin until it was substantially colorless. The solvent was removed under vacuum, and the mixture was washed three times with N,N'-dimethylformamide (10 mL for each washing). (6) Deprotection and coupling of Fmoc-Gly-Gly-OH An Fmoc-deprotection reagent solution (N,N'-dimethylformamide / piperidine = 4:1, containing 1% HOBt, 10 mL) was added to the solid-phase synthesis tube in the previous step. The mixture was stirred for 10 min and completely filtered under vacuum. Then the same Fmoc-deprotection reagent solution (10 mL) was added, and the mixture was stirred for 10 min and completely filtered under vacuum. Subsequently, the mixture was washed four times with N,N'-dimethylformamide (20 mL for each washing). The resin was tested with ninhydrin and exhibited a dark blue color. Fmoc-Gly-Gly-OH (567 mg), HATU (576 mg), and HOAT (208 mg) were weighed into a PE tube, DMF (12 mL) was added, and the mixture was mixed well until complete dissolution. Finally, diisopropylethylamine (600 pL) was added, and the mixture was shaken sufficiently and mixed well. The solution described above was added to the synthesis tube. Then, the mixture was bubbled with nitrogen from the bottom of the solid-phase synthesis tube for about 2 h. The resin was tested using ninhydrin until it was substantially colorless. The solvent was removed under vacuum, and the mixture was washed three times with N,N'-dimethylformamide (10 mL for each washing). (7) Deprotection and condensation of Boc-Gly-OH An Fmoc-deprotection reagent solution (N,N'-dimethylformamide / piperidine = 4:1, containing 1% HOBt, 10 mL) was added to the solid-phase synthesis tube in the previous step. The mixture was stirred for 10 min and completely filtered under vacuum. Then the same Fmoc-deprotection reagent solution (10 mL) was added, and the mixture was stirred for 10 min and completely filtered under vacuum. Subsequently, the mixture was washed four times with N,N'-dimethylformamide (10 mL for each washing). The resin was tested with ninhydrin and exhibited a dark blue color. Boc-Gly-OH (280 mg), HATU (576 mg), and HOAT (208 mg) were weighed into a PE tube, DMF (12 mL) was added, and the mixture was mixed well until complete dissolution. Finally, diisopropylethylamine (600 pL) was added, and the mixture was shaken sufficiently and mixed well. The solution described above was added to the synthesis tube. Then, the mixture was bubbled with nitrogen from the bottom of the solid-phase synthesis tube for about 2 h. The resin was tested using ninhydrin until it was substantially colorless. The solvent was removed under vacuum, and the mixture was washed three times with N,N'-dimethylformamide (10 mL for each washing). (8) Deprotection and coupling of p-iodophenylbutyric acid A Dde-deprotection reagent solution (N,N'-dimethylformamide / hydrazine hydrate = 95:5, 10 mL) was added to the solid-phase synthesis tube in the previous step. The mixture was stirred for 10 min. Then, the mixture was completely filtered under vacuum. The same Dde-deprotection reagent solution (10 mL) was added, and the mixture was stirred for 10 min and completely filtered under vacuum. Subsequently, the mixture was washed four times with N,N'-dimethylformamide (10 mL for each washing). The resin was tested with ninhydrin and exhibited a dark blue color. p-Iodophenylbutyric acid (696 mg) and Oxyma (864 mg) were weighed into a PE tube, N,N'-dimethylformamide (10 mL) was added, and the mixture was mixed well until complete dissolution. Finally, DIC (600 pL) was added, and the mixture was shaken sufficiently and mixed well. The solution described above was added to the synthesis tube. Then, the mixture was bubbled with nitrogen from the bottom of the solid-phase synthesis tube for about 2 h. The resin was tested using ninhydrin until it was substantially colorless. The solvent was removed under vacuum, and the mixture was washed twice with N,N'-dimethylformamide (10 mL for each washing) and washed three times with dichloromethane (10 mL for each washing). The solvent was removed under vacuum, and then the resin was air-dried to a free-flowing state. (9) Cleavage Dichloromethane (7 mL) and hexafluoroisopropanol (3 mL) were added to a round-bottom flask, and the mixture was mixed well. The resin obtained in the previous step was added to the solution described above. The mixture was stirred for about 2 h. The mixture was filtered, and the resin was washed with a small amount of dichloromethane. The resulting filtrate was completely concentrated under reduced pressure to give an oily crude peptide, which was weighed. (10) Coupling of DOTA DOTA (916 mg) and HOBt (212 mg) were weighed into a PE tube, N,N'-dimethylformamide (1 mL) was added, and the mixture was mixed well until complete dissolution. The solution described above was added to a 50 mL round-bottom flask containing the crude peptide, and dichloromethane (5 mL) was added. The mixture was shaken well, and DIC (300 pL) was slowly added dropwise. The mixture was stirred overnight. The solution was concentrated to dryness by a rotary evaporator to give a pure product. (11) Deprotection and purification Preparation of 10 mL of a conventional cleavage solution: phenol (500 mg), Tips (1 mL), and purified water (0.5 mL), with the volume brought to 10 mL by using TFA. The deprotection solution described above was poured into the pure product obtained in (8), and the mixture was stirred for 2 h. Cold ethyl ether (20 mL) was added, and sufficient precipitation was achieved. 5 The mixture was then centrifuged at 3500 rpm for 3 min using a centrifuge. After the centrifugation was completed, the supernatant was discarded, and the mixture was centrifuged three times. The mixture was air-dried at room temperature. The resulting pure product was separated by semi-preparative liquid chromatography and lyophilized to give LP11 (20 mg, purity: 96.46%). LC-MS analysis showed [1 / 2M+H]+ = 957.25, and the value is consistent with 10 the theoretical value. Example 13: Synthesis of Compound LP12 15 Referring to the synthetic method for compound LP4 in Example 5, compound LP12 was synthesized according to the route shown above. The LC-MS analysis value is consistent with the theoretical value. Example 14: Synthesis of Compound LP13 NHDde BocHN' Frnoc-Lys(Dde)-OH FmocHN' 20¾ HFIP / DCM LP13 Referring to the synthetic method for compound LP4 in Example 5, compound LP13 was synthesized according to the route shown above. LC-MS analysis showed [1 / 2M+H]+ = 816.70, and the value is consistent with the theoretical value. 5 Example 15: Synthesis of Compound LP14 NHDde NHDde NHDde h_f*Fm«:-Lys(Dde)-OH HjW^ ' V-------* 1,20%Piperidine'DMF q / r\ 2.Fmoe-PEG|-OH H I H 7----* h « H s r« n ri rail - a ^hfwocm LP14 Referring to the synthetic method for compound LP4 in Example 5, compound LP14 was synthesized according to the route shown above. LC-MS analysis showed [1 / 2M+H]+ = 665.50, and the value is consistent with the theoretical value. Example 16: Synthesis of Compound H0274 5 The positive control targeting radionuclide conjugate precursor H0274 was synthesized with reference to the method in the literature Mol. Pharmaceutics 2018, 15, 934-946. LC-MS analysis showed [M+H]+ = 1330.95, and the value is consistent with the theoretical value. Example 17: Preparation of Monoclonal Single-Domain Antibodies Specifically Targeting 10 Human Prostate-Specific Membrane Antigen (PSMA) 17.1 Vector construction and expression Monoclonal single-domain antibodies with high affinity and specifically targeting human PSMA were selected, the sequences of which are shown in the table below._________________ No. Sequence CDR Ab60 QVQLQESGGGSVQAGGSLRLSCTAPGYTDSN NYYMS (SEQ ID NO: 1) YYMSWFRQAPGKEREWVAGVNTGRGSTSYA GVNTGRGSTSYADSVK DSVKGRFTISQDNAKNTMFLQMNSLKPEDTAI G(SEQ ID NO: 2) YYCAVAACHFCDSLPKTQDEYILWGQGTQVT AACHFCDSLPKTQDEY VSS (SEQ ID NO: 10) IL(SEQ ID NO: 3) Ab61 QVQLQESGGGSVQAGGSLRLSCARSGWPYST TYSMN (SEQ ID NO: 4) YSMNWFRQAPGKEREAVAGISSTMSGIIFAES GISSTMSGIIFAESKAG( SEQ ID NO: 5) KAGQFTISQDNAKNTVYLQMNNLKPEDTAIY YCAARRDYSLSSSSDDFDYWGQGTQVTVSS RRDYSLSSSSDDFDY (SEQ ID NO: 6) (SEQ ID NO: 11) Ab62 EVQLVESGGGVVQPGRSLRLSCAASGFSFSGY GYGMH (SEQ ID NO: 7) GMHWVRQAPGKGLEWVAYISYDGSNKYYAD YISYDGSNKYYADSVK G(SEQ ID NO: 8) DPAWGLRLGESSSYDF DI(SEQ ID NO: 9) SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY YCAKDPAWGLRLGESSSYDFDIWGQGTMVT VSSGALPETGGHHHHHH(SEQ ID NO: 12) Ab63 EVQLVESGGGVVQPGRSLRLSCAASGFSFSGY GYGMH(SEQ ID NO: 7) GMHWVRQAPGKGLEWVAYISYDGSNKYYAD YISYDGSNKYYADSVK G(SEQ ID NO: 8) DPAWGLRLGESSSYDF SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY YCAKDPAWGLRLGESSSYDFDIWGQGTMVT VSSGGGGSGGGGSLPETGG (SEQ ID NO: 13) DI(SEQ ID NO: 9) Note: Antibodies Ab60 and Ab61 were unmodified VHHs; antibody Ab62 was a modified VHH: its C-terminus was sequentially linked to a linker sequence (GA), a recognition sequence for a sortase enzyme donor substrate (LPETGG, SEQ ID NO: 18), and a purified sequence (HHHHHH, SEQ ID NO: 20), and under the action of the sortase enzyme, antibody Ab62 cleaved off sequence GGHHHHHH (SEQ ID NO: 19) and was linked to glycine in formula (I); antibody Ab63 was a modified VHH: its C-terminus was sequentially linked to a linker sequence (GGGGSGGGGS, SEQ ID NO: 15) and a recognition sequence for a sortase enzyme donor substrate (LPETGG, SEQ ID NO: 18), and under the action of the sortase enzyme, antibody Ab63 cleaved off sequence GG and was linked to glycine in formula (I). To generate an expression vector encoding the anti-human PSMA single-domain antibody, the nucleic acid sequence of the single-domain antibody was cloned into a pCDNA 3.4 vector; the vector was transformed into E. coli competent cells by ligation, monoclones were picked for sequencing confirmation, positive clones were cultured and amplified for plasmid extraction, and antibody eukaryotic expression plasmids were obtained and transformed into Chinese hamster ovary cells (CHO cells) adapted to suspension growth by electroporation. After the electroporation was completed, the cells in the electroporation cuvette were evenly aliquoted into shake flasks containing 100 mL of the culture medium and incubated statically for 40 min. After the incubation was completed, the shake flasks were incubated at 37 °C and 120 rpm with 8% CO2, and the antibodies were collected. 17.2 Purification of antibodies The antibodies were purified by the Ni affinity chromatography column. The chromatography column was first equilibrated with 20 mL of 1x PBS at a flow rate of 1 mL / min. After loading, 20 mL of 1x PBS and 5 mM imidazole (pH 8.0) were passed through the column at a flow rate of 1 mL / min to remove impurities. Then the sample was eluted using 150 mM imidazole (pH 8.0) at 1 mL / min and collected in separate tubes, and the absorbance value at 280 nm was read using a NanoDrop instrument. The high-concentration protein was transferred to a dialysis bag and dialyzed in a beaker containing 50 mM Tris + 150 mM NaCl (pH 8.0). Example 18: Preparation of Conjugate Ab62-LP1 18.1 Experimental principle Immobilized Sortase specifically recognizes and cleaves an enzyme-recognition site (e.g., LPETGG) on an engineered small antibody fragment (such as the Fab, scFv, nanobody, sdAb, and affibody), and site-specifically conjugates the fragment with a structure of a radionuclide-linked chelating group (i.e., formula II), so as to form the corresponding conjugate. 18.2 Preparation of immobilized Sortase Halo-Sortase and Chloro resin (see WO2022160156A) were mixed and incubated at room temperature for 10 min to 24 h, and then rinsed with a buffer of 20 mM Tris-HCl and 150 mM NaCl (pH = 6.0-10.0). The immobilized Sortase after being rinsed was assayed for activity. After passing the assay, the immobilized ligase (i.e., the Sortase enzyme) resin (Ligase Immobilized Resin) was washed with 20 mM Tris-HCl and 150 mM NaCl and stored at 4 °C for later use. 18.3 Conjugation and purification Single-domain antibody Ab62 was treated by ultrafiltration, dialysis, or desalting column chromatography, and the buffer was replaced with a solution of 50 mM Tris-HCl and 150 mM NaCl (pH = 5.0-8.0). Single-domain antibody Ab62 and compound LP1 were thoroughly mixed according to an appropriate molar ratio (1:1 to 1:100) and added to a certain amount of the immobilized Sortase enzyme. A certain amount of the buffer solution and the CaCl2 solution were added. The mixture was mixed well. The system described above was subjected to a conjugation reaction at 4-40 °C for 0.5-20 h. After the reaction was completed, the mixture was centrifuged, and the supernatant was collected. An appropriate amount of the EDTA solution was added to the supernatant, and the mixture was incubated at room temperature for 0.1-5 h. Subsequently, purification, ultrafiltration, or dialysis was performed to remove unreacted small molecules. Purified conjugate Ab62-LP1 was stored in an acetic acid buffer of an appropriate pH value at 4 °C or -80 °C for later use. 18.4 Detection of number of chelating groups in conjugate Ab62-LP1 (DAR value) The number of structures of radionuclide-linked chelating groups conjugated to the singledomain antibody in conjugate Ab62-LP1 (DAR value) was detected using HIC-HPLC, and the specific procedures were as follows: Chromatographic column: Proteomix HIC Butyl-NP5, 4.6 x 100 mm, 5 um, Non-Porous chromatographic column (manufacturer: Sepax, PN: 431NP5-4610); mobile phase A: 1.5 M ammonium sulfate + 20 mM phosphate-buffered salt (pH 7.0); mobile phase B: a mixed solution of 20 mM phosphate-buffered salt (pH 7.0) and isopropanol, in a volume ratio of 7:3; flow rate: 0.8 mL / min; detection wavelength: 280 nm. elution gradient: 0-8 min, phase B from 10% to 100%. The detection results are shown in FIG. 1. According to the peak area, it was calculated that an average of about 0.79 structures of radionuclide-linked chelating groups were conjugated to each single-domain antibody Ab62, i.e., the DAR of conjugate Ab62-LP1 was 0.79. 18.5 Purity detection of conjugate Ab62-LP1 The purity of conjugate Ab62-LP1 was detected by SEC-HPLC, and the specific procedures were as follows: Chromatographic column: TSKgel G3000SWXL 7.8 mm I.D. x 30 cm, 5 pm chromatographic column (manufacturer: Tosoh, PN: 0008541); mobile phase: a mixed solution of 2x PBS and acetonitrile in a volume ratio of 90:10; flow rate: 1.0 mL / min; detection wavelength: 280 nm. The detection results are shown in FIG. 2. The purity of conjugate Ab62-LP1 could be calculated to be close to 100% according to the peak area. Example 19: Preparation of Conjugate Ab62-LP0, Conjugate Ab62-LP2, Conjugate Ab62-LP3, and Conjugate Ab63-LP1 Referring to the preparation method in Example 18, compound LP1 was replaced with compound LP0, compound LP2, and compound LP3 to prepare conjugate Ab62-LP0, conjugate Ab62-LP2, and conjugate Ab62-LP3, respectively; single-domain antibody Ab62 was replaced with single-domain antibody Ab63 to prepare conjugate Ab63-LP1. The resulting conjugates _were further purified and subjected to DAR tests. The results are shown in the table below: Conjugate No. DAR value Purity Ab62-LP0 0.73 100% Ab62-LP2 0.72 100% Ab62-LP3 0.70 100% Ab63-LP1 0.83 100% Example 20: Affinity Assay of Conjugates (SPR Method) The affinity of single-domain antibody Ab62 and conjugates thereof (Ab62-LP1, Ab62-LP2, and Ab62-LP3) for human PSMA was measured on a Biacore T200 molecular interaction instrument. First, a 1x HBS-EP solution was prepared as the running buffer for the entire assay. The human PSMA protein was diluted to 15 pg / mL in a 10 mM sodium acetate solution (pH 4.5) and was coupled onto channels 2-4 of a Series S CM5 biochip at about 2500 RU using amino coupling reagent EDC-NHS. Subsequently, quenching was performed in a 1 M ethanolamine solution (pH 8.5). Channel 1 was used as a blank subtraction channel and left empty without processing. The test single-domain antibody and conjugates were serially two-fold diluted with the 1x HBS-EP solution from a top concentration of 10 nM down to 0.625 nM. A single-cycle mode was used to measure the affinity of samples at different concentrations for the human-PSMA-coupled Series S CM5 biochip sequentially from low analyte concentration to high analyte concentration. The assay temperature was 25 °C, the data-acquisition frequency was 10 Hz, and the flow rate was 30 gL / min. The association time and dissociation time were 120 s and 600 s, respectively. After data acquisition was completed, blank subtraction was performed on the sensorgram traces of each sample using Biacore T200 Evaluation Software 3.2.1 software. Kinetic analysis with 1:1 binding-model fitting was performed using the blank-subtracted sensorgram traces, and the affinity strengths for binding of the single-domain antibody and conjugates to the human PSMA antigen were finally calculated. The results are shown in the table below: Sample No. KD (M) Ab62 1.394E-10 Ab62-LP1 3.393E-10 Ab62-LP2 3.610E-10 Ab62-LP3 3.865E-10 As can be seen from the results in the above table, the affinity of conjugate Ab62-LP1, conjugate Ab62-LP2, and conjugate Ab62-LP3 was not significantly different from that of Ab62, indicating that the conjugation of different payload-linkers did not affect the affinity of the single-domain antibody. Example 21: Affinity Assay of Conjugates (FACS Method) Using the PSMA+ PC-3 tumor cell line, the affinity of conjugate Ab62-LP1, conjugate Ab62-LP2, conjugate Ab62-LP3, and single-domain antibody Ab62 for PSMA-positive tumor cells can be determined by the conventional FACS method, and the results are shown in FIG. 3. It can be seen that the conjugation of different payload-linkers did not affect the affinity of the single-domain antibody for tumor cells. Example 22: Endocytic Activity Assay of Conjugates Using the PSMA+ PC-3 tumor cell line, the endocytic activity of PSMA-positive tumor cells on conjugate Ab62-LP1, conjugate Ab62-LP2, conjugate Ab62-LP3, and single-domain antibody Ab62 can be determined by the conventional endocytic activity assay method, and the results are shown in FIG. 4. It can be seen that the conjugation of different payload-linkers did not affect the endocytosis of the single-domain antibody by PSMA-positive tumor cells. Example 23: Preparation of Radionuclide Conjugate 68Ga-Ab62-LP1 Conjugate Ab62-LP1 (about 288 gg) was diluted in about 200 gL of a 1 M NaOAc buffer (about pH 4.5), and a [68Ga]Ga3+ solution (5 mCi, about 1 mL) was added to the system. The mixture was then incubated at 20-50 °C for 10-120 min. The reaction solution was subjected to SEC purification using a PD-10 desalting column and eluted with a 0.01 M sterile PBS buffer (about pH 7.4), and the desired fraction was collected. The specific activity was detected to be about 0.01 mCi / pg, and the chemical purity and radiochemical purity were detected by radio-HPLC. The results are shown in FIG. 5 and FIG. 6, respectively. Example 24: Preparation of Radionuclide Conjugate 177Lu-Ab62-LP1 Preparation 1: Conjugate Ab62-LP1 (about 200-1000 pg) was diluted in about 200-500 pL of a 0.5 M NH4OAc buffer (about pH 4.0), and a [177Lu]Lu3+ solution (5-250 mCi) was added to the system. The mixture was then incubated at 20-50 °C for 10-120 min. The reaction solution was subjected to SEC purification using a PD-10 desalting column and eluted with a 0.01 M sterile PBS buffer (about pH 7.4), and the desired fraction was collected. The specific activity was detected to be about 10-150 mCi / mg, and the chemical purity and radiochemical purity were detected by radio-HPLC. The results are shown in FIG. 7 and FIG. 8, respectively. Preparation 2: Conjugate Ab62-LP1 (about 300 pg) was diluted in about 500 pL of a 1 M NaOAc buffer (about pH 4.5), and a [177Lu]Lu3+ solution (20-25 mCi) was added to the system. The mixture was then incubated at 20-50 °C for 10-120 min. The reaction solution was subjected to SEC purification using a PD-10 desalting column and eluted with a 0.01 M sterile PBS buffer (about pH 7.4), and the desired fraction was collected to give conjugate 177Lu-Ab62-LP1. An appropriate amount of the NaVc solution (100 mg / mL) was added to the solution. The specific activity was detected to be about 0.04 mCi / pg, and the chemical purity and radiochemical purity were detected by radio-HPLC. The results are shown in FIG. 9 and FIG. 10, respectively. Example 25: Preparation of Radionuclide Conjugates 177Lu-Ab62-LP2, 177Lu-Ab62-LP3, and 177Lu-PSMA-617 Preparation 1: Referring to the method of Preparation 1 of Example 24, conjugate Ab62-LP1 was separately replaced with conjugate Ab62-LP2, conjugate Ab62-LP3, and PSMA-617 (CAS: 1702967-37-0) for preparation to give conjugates 177Lu-Ab62-LP2, 177Lu-Ab62-LP3, and 177Lu-PSMA-617, whose chemical purity and radiochemical purity determined by radio-HPLC after purification both met the requirements for subsequent tests. Preparation 2: Referring to the method of Preparation 2 of Example 24, conjugate Ab62-LP1 was separately replaced with conjugate Ab62-LP2, conjugate Ab62-LP3, and PSMA-617 (CAS: 1702967-37-0) for preparation to give conjugates 177Lu-Ab62-LP2, 177Lu-Ab62-LP3, and 177Lu-PSMA-617, whose chemical purity and radiochemical purity determined by radio-HPLC after purification both met the requirements for subsequent tests. Example 26: Serum Stability Test of Radionuclide Conjugates 177Lu-Ab62-LP1, 177Lu-Ab62-LP2, 177Lu-Ab62-LP3, and 177Lu-PSMA-617 20-50 pL of each of radionuclide conjugates 177Lu-Ab62-LP1, 177Lu-Ab62-LP2, 177Lu-Ab62- LP3, and 177Lu-PSMA-617 prepared by the methods of Preparation 2 of Example 24 and Preparation 2 of Example 25 was mixed with an equal volume of the mouse serum, and the mixture was pipetted, mixed well, and incubated in a thermostatic incubator at 37 °C. Samples were respectively taken at 0 h, 8 h, and 24 h of incubation for radioactive thin-layer scanning analysis to detect the radiochemical purity of the system. The detection results showed that the radiochemical purity of radionuclide conjugate 177Lu-PSMA-617 at 0 h was 99.2%, the radiochemical purity at 8 h was slightly reduced to 99.1%, but the radiochemical purity at 24 h was reduced to 97.0%, while the radiochemical purity of radionuclide conjugates 177Lu-Ab62-LP1, 177Lu-Ab62-LP2, and 177Lu-Ab62-LP3 in serum at 0 h, 8 h, and 24 h was unchanged, which is 100%. Radionuclide conjugates 177Lu-Ab62-LP1, 177Lu-Ab62-LP2, and 177Lu-Ab62-LP3 exhibited higher stability relative to radionuclide conjugate 177Lu-PSMA-617. Example 27: Evaluation of In Vivo Tumor-Inhibitory Activity of Different 177Lu-Labeled Radionuclide Conjugates in PSMA+ LNCaP Tumor-Bearing Murine Model Radionuclide conjugates 177Lu-Ab62-LP1, 177Lu-Ab62-LP2, and 177Lu-Ab62-LP3 (control 1) and radionuclide conjugate 177Lu-PSMA-617 (control 2) prepared by the methods of Preparation 2 of Example 24 and Preparation 2 of Example 25, respectively, were injected into PSMA+ LNCaP tumor-bearing mice, and then the changes in tumor volume and body weight of the mice were recorded at different time points, as shown in the table below. Group Test substance Dose (MBq / mouse) Frequency of administration Route of administration Tumor volume (mm3, mean ± SE) Day 0 Day 6 Day 13 Day 20 Day 27 G1 Normal saline - Single dose Intravenous injection 159.3± 10.7 444.0± 45.2 1682.8 ±488.2 2728.3 ±394.6 N / A G2 177Lu- PSMA-617 10 Single dose Intravenous injection 159.7± 11.0 145.2± 14.4 47.2± 19 210.8± 73.9 1173.9 ±426.6 G3 177Lu- Ab62-LP1 10 Single dose Intravenous injection 159.5± 10.5 87.5.0± 9.1 66.0± 22.9 219.9± 106.3 843.9± 348.3 G4 177Lu- Ab62-LP2 10 Single dose Intravenous injection 159.4± 9.8 64.8± 9.5 0.0± 0.0 0.0± 0.0 0.0± 0.0 G5 177Lu- Ab62-LP2 5 Single dose Intravenous injection 158.4± 11.0 68.9± 12.9 35.5± 17.9 7.3± 6.0 282.2± 194.0 G6 177Lu- Ab62-LP3 10 Single dose Intravenous injection 158.9± 11.9 216.2± 8.3 239.5± 68.4 667.5± 174.2 1808.1 ±313.5 It can be seen that radionuclide conjugate 177Lu-Ab62-LP2 exhibited the highest tumor- inhibitory activity, while the activity of radionuclide conjugate 177Lu-Ab62-LP1 was also higher than that of radionuclide conjugate 177Lu-Ab62-LP3 (control 1) and that of radionuclide conjugate 177Lu-PSMA-617 (control 2). The body weight of the mice tended to recover subsequently, indicating that the RDCs of the present application were safe and well-tolerated. Example 28: Preparation of Radionuclide Conjugate 64Cu-Ab62-LP2 Conjugate Ab62-LP2 (about 100 pg) was diluted in about 200 pL of a 1 M NaOAc buffer (about pH 4.5), and a [64Cu]Cu2+ solution (6 mCi, about 300 pL) was added to the system. The mixture was then incubated at 20-50 °C for 10-120 min. The reaction solution was subjected to SEC purification using a PD-10 desalting column and eluted with a 0.01 M sterile PBS buffer (about pH 7.4), and the desired fraction was collected to give radionuclide conjugate 64Cu-Ab62-LP2. The specific activity was detected to be about 0.19 mCi / pg, and the chemical purity and radiochemical purity were detected by radio-HPLC. The results are shown in FIG. 11 and FIG. 12, respectively. Example 29: Preparation of Radionuclide Conjugates 64Cu-Ab62-LP1, 64Cu-Ab62-LP3, and 64Cu-PSMA-617 Referring to the method in Example 28, conjugate Ab62-LP2 was separately replaced with conjugate Ab62-LP1, conjugate Ab62-LP3, and PSMA-617 (CAS: 1702967-37-0) for preparation to give radionuclide conjugates 64Cu-Ab62-LP1, 64Cu-Ab62-LP3, and 64Cu-PSMA-617, whose chemical purity and radiochemical purity determined by radio-HPLC after purification were about 100%. Example 30: Stability Investigation of Radionuclide Conjugates 64Cu-Ab62-LP1, 64Cu-Ab62-LP2, 64Cu-Ab62-LP3, and 64Cu-PSMA-617 in Murine Serum A certain amount of radionuclide conjugates 64Cu-Ab62-LP1, 64Cu-Ab62-LP2, and 64Cu-Ab62-LP3 and conjugate 64Cu-PSMA-617 were separately mixed and incubated with the murine serum, and samples were taken at 0 h, 8 h, and 24 h for detection of the radiochemical purity of the samples using Radio-iTLC. The results are shown in FIG. 13. It can be seen that radionuclide conjugates 64Cu-Ab62-LP1, 64Cu-Ab62-LP2, and 64Cu-Ab62-LP3 exhibited higher stability with almost no degradation relative to 64Cu-PSMA-617. Example 31: Uptake and Endocytosis of Radionuclide Conjugates 64Cu-Ab62-LP1, 64Cu-Ab62-LP2, 64Cu-Ab62-LP3, and 64Cu-PSMA-617 in Tumor Cells PSMA+ LNCaP and PSMA- PC-3 tumor cells were separately seeded in multi-well plates and allowed to adhere and grow overnight. The cells were washed with PBS, and a certain amount of the culture medium was added per well, followed by addition of radionuclide conjugates 64Cu-Ab62-LP1, 64Cu-Ab62-LP2, 64Cu-Ab62-LP3, and 64Cu-PSMA-617 per well, respectively. Replicate wells were used for each sample. Then, the mixture was diluted with normal saline and incubated in the plate for 4 h. To detect the radionuclide conjugate uptake activity by tumor cells, the cells were washed three times with ice-cold PBS, a NaOH lysis solution was added to the cell samples, and measurement was performed in a Y-counter. To detect the endocytosis of each conjugate by tumor cells, the cells were first washed with ice-cold PBS, incubated in an acidic buffer for 10 min, and washed with ice-cold PBS. A NaOH lysis solution was added to the cell samples, and measurement was performed in a Y-counter. The results are shown in FIG. 14. It can be seen from the results that the activity of three single-domain antibody radionuclide conjugates 64Cu-Ab62-LP1, 64Cu-Ab62-LP2, and 64Cu-Ab62-LP3 for uptake and endocytosis in PSMA+ LNCaP tumor cells was comparable to that of 64Cu-PSMA-617, and they were hardly taken up by PSMA- PC-3 tumor cells. Example 32: Positron Emission Tomography (PET) Imaging Study of Different 64Cu-Labeled Radionuclide Conjugates in PSMA+ LNCaP Tumor-Bearing Murine Model Radionuclide conjugates 64Cu-Ab62-LP1, 64Cu-Ab62-LP2, and 64Cu-Ab62-LP3 (control 3) and radionuclide conjugate 64Cu-PSMA-617 (control 4) were separately injected into PSMA+ LNCaP tumor-bearing murines. The tumor-bearing murines were then scanned at different time points using PET / CT, and the corresponding images and the amount of 64Cu in tumors and key organ tissues were collected. The results are shown in the table below._______________________ 64Cu- PSMA-617 64Cu-Ab62- LP1 64Cu-Ab62-LP2 64Cu-Ab62- LP3 24h 48h 24h 48h 24h 48h 24h 48h Ratio of 64Cu in tumor to that in blood or normal organs Tumor / blood 4 4 35 17 47 42 35 47 Tumor / kidney 2 1 4 4 6 9 1 3 Tumor / liver 1 1 5 3 13 10 3 3 Tumor / salivary gland 4 4 41 24 58 110 53 34 Exposure / A UC1-48 h (%ID / g*h) Tumor 383.2±4.90 447.3±16.86 1114±32.27 261.8±24.60 Blood 82.74±4.39 15.03±5.00 95.34±11.87 6.15±1.57 Kidney 190.6±4.786 167.8±13.96 233.3±10.32 198.5±10.43 Liver 498.8±10.49 84.47±4.75 116.1±9.83 66.73±6.14 It can be seen that 64Cu-Ab62-LP1 and 64Cu-Ab62-LP2 had higher 64Cu enrichment (AUC1-48h) and longer retention time in tumors relative to 64Cu-Ab62-LP3 (control 3) and conjugate 64Cu-PSMA-617 (control 4). Furthermore, relative to the other three radionuclide conjugates, 64Cu- Ab62-LP2 showed a relatively significant increase in nearly all ratios of 64Cu enrichment amount in tumors to that in the blood and key normal tissues at 24 h and 48 h. Example 33: Preparation of Conjugates Ab62-LP5, Ab62-LP6, Ab62-LP10, and Ab62-LP11 Referring to the preparation method in Example 18, compound LP1 was replaced with compound LP5, compound LP6, compound LP10, and compound LP11 to prepare conjugate Ab62-LP5, conjugate Ab62-LP6, conjugate Ab62-LP10, and conjugate Ab62-LP11, respectively. The resulting conjugates were further purified and subjected to a DAR test. The DAR value and purity analysis (monomer ratio) results obtained are shown in the table below: Conjugate No. DAR value Purity Ab62-LP5 0.79 100% Ab62-LP6 0.72 99.66% Ab62-LP10 0.83 99.59% Ab62-LP11 0.90 99.02% Example 34: Preparation of Radionuclide Conjugates 64Cu-Ab62-LP5, 64Cu-Ab62-LP6, 64Cu-Ab62-LP10, and 64Cu-Ab62-LP11 Referring to the method in Example 28, the conjugate Ab62-LP2 was replaced with conjugates Ab62-LP5, Ab62-LP6, Ab62-LP10, and Ab62-LP11 to prepare radionuclide conjugates 64Cu-Ab62-LP5, 64Cu-Ab62-LP6, 64Cu-Ab62-LP10, and 64Cu-Ab62-LP11, respectively. After purification, the chemical purity and the radioactive purity were all about 100%, as detected by radio-HPLC. Example 35: Positron Emission Tomography (PET) Imaging Study of Different 64Cu-Labeled Radionuclide Conjugates in PSMA+ LNCaP Tumor-Bearing Murine Model Radionuclide conjugates 64Cu-Ab62-LP2, 64Cu-Ab62-LP5, 64Cu-Ab62-LP6, 64Cu-Ab62-LP10, and 64Cu-Ab62-LP11 were separately injected into PSMA+ LNCaP tumor-bearing mice. The tumor-bearing mice were then scanned at different time points using PET / CT, and the corresponding images and the amount of 64Cu in tumors and key organ tissues were collected. The results are shown in the table below. 64Cu-Ab62- LP5 64Cu-Ab62- LP6 64Cu-Ab62- LP10 64Cu-Ab62- LP11 24h 48h 24h 48h 24h 48h 24h 48h Ratio of 64Cu Tumor / blood 18.5 13.5 40.2 58.5 10.3 19.3 4.0 6.8 in tumor to that in blood or normal organs Tumor / kidney 3.1 3.1 1.4 2.2 3.6 4.3 3.9 4.7 Tumor / liver 2.9 3.0 6.4 3.2 5.1 4.9 3.4 3.9 Exposure / AU C1-72 h (%ID / g*h) Tumor 914±37.2 535.1±41.7 1439±56.1 1757±43.9 Blood 41.5±1.7 9.9±2.4 203.1±14.9 457.5±35.2 Kidney 390.8±19.4 361.9±37.0 420.7±17.6 479.4±18.0 Liver 258±8.6 105.2±5.8 331±16.1 570±22.3 It can be seen that the radionuclide conjugates 64Cu-Ab62-LP5, 64Cu-Ab62-LP6, 64Cu-Ab62-LP10, and 64Cu-Ab62-LP11 all had relatively high 64Cu enrichment amount (AUC) in tumors. In the tumor-bearing murine model, at 1-72 h after administration, the order of 64Cu enrichment amount in the blood was: 64Cu-Ab62-LP11 > 64Cu-Ab62-LP10 > 64Cu-Ab0362-LP5 > 64Cu-Ab0362-LP6. The order of 64Cu enrichment amount in the tumor was completely consistent with the order in the blood, and there was no significant difference in the 64Cu enrichment amount of these four radionuclide conjugates in the kidney. Example 36: Preparation of Monoclonal Single-Domain Antibody Specifically Targeting Human Epidermal Growth Factor Receptor 2 (HER2) 36.1 Vector construction and expression A monoclonal single-domain antibody with high affinity and specifically targeting human HER2 was selected, the sequences of which are shown in the table below.__________________ No. Sequence CDR Ab5 QVQLQESGGGSVQAGGSLKLTCAASGYIF SCGMG (SEQ ID NO: 23) NSCGMGWYRQSPGRERELVSRISGDGDT RISGDGDTWHKESVKG (SEQ ID NO: 24) WHKESVKGRFTISQDNVKKTLYLQMNSL KPEDTAVYFCAVCYNLETYWGQGTQVTV CYNLETY(SEQ ID NO: SSGALPETGGHHHHHH (SEQ ID NO: 22) 25) To generate an expression vector encoding the anti-human HER2 single-domain antibody, the nucleic acid sequence of the single-domain antibody was cloned into a pCDNA 3.4 vector; the vector was transformed into E. coli competent cells by ligation, monoclones were picked for sequencing confirmation, positive clones were cultured and amplified for plasmid extraction, and antibody eukaryotic expression plasmids were obtained and transformed into Chinese hamster ovary cells (CHO cells) adapted to suspension growth by electroporation. After the electroporation was completed, the cells in the electroporation cuvette were evenly aliquoted into shake flasks containing 100 mL of the culture medium and incubated statically for 40 min. After the incubation was completed, the shake flasks were incubated at 37 °C and 120 rpm with 8% CO2, and the antibodies were collected. 36.2 Purification of antibody The antibodies were purified by the Ni affinity chromatography column. The chromatography column was first equilibrated with 20 mL of 1x PBS at a flow rate of 1 mL / min. After loading, 20 mL of 1x PBS and 5 mM imidazole (pH 8.0) were passed through the column at a flow rate of 1 mL / min to remove impurities. Then the sample was eluted using 150 mM imidazole (pH 8.0) at 1 mL / min and collected in separate tubes, and the absorbance value at 280 nm was read using a NanoDrop instrument. The high-concentration protein was transferred to a dialysis bag and dialyzed in a beaker containing 50 mM Tris + 150 mM NaCl (pH 8.0). Example 37: Preparation of Conjugate Ab5-LP10 Referring to the preparation method in Example 18, compound LP1 was replaced with compound LP10, and single-domain antibody Ab62 was replaced with single-domain antibody Ab5 to prepare conjugate Ab5-LP10. The resulting conjugate was further purified and subjected to a DAR test. The DAR value and purity analysis (monomer ratio) results obtained are shown in the table below: Conjugate No. DAR value Purity Ab5-LP10 0.98 97.38% Example 38: Affinity Assay (SPR Method) Referring to the method in Example 20, the affinity strength was tested by replacing the human PSMA protein with the human HER2 protein and replacing single-domain antibody Ab62 with single-domain antibody Ab5. The results are shown in the table below: ,______________________ Sample No. ka(1 / Ms) Kd(1 / s) KD (M) Ab5 4.78E+4 9.17E-4 1.92E-8 Example 39: Preparation of Radionuclide Conjugate 64Cu-Ab5-LP10 Referring to the preparation method in Example 28, conjugate Ab62-LP2 was replaced with conjugate Ab5-LP10 to prepare radionuclide conjugate 64Cu-Ab5-LP10, whose chemical purity and radiochemical purity determined by radio-HPLC after purification both met the requirements for subsequent tests. Example 40: Positron Emission Tomography (PET) Imaging Study of 64Cu-Labeled Radionuclide Conjugate in Tumor-Bearing Murine Model SKOV-3 with High HER2 Expression Radionuclide conjugate 64Cu-Ab5-LP10 was injected into SKOV-3 tumor-bearing murines with high HER2 expression, and then the tumor-bearing murines were scanned at different time points using PET / CT. The corresponding images and the amount of 64Cu in tumors and key organ tissues were collected, and the results are shown in the table below. 64Cu-Ab5-LP10 24h 48h Ratio of 64Cu in tumor to that in blood or normal organs Tumor / blood 11.06 9.45 Tumor / kidney 1.06 1.60 Tumor / liver 5.77 4.22 Exposure / AUCi-72 h (%ID / g*h) Tumor 1035±89.15 Blood 219.8±9.467 Kidney 1010±50.13 Liver 287.7±5.414 It can be seen that, similar to 64Cu-Ab62-LP1 and 64Cu-Ab62-LP2 in Example 32, radionuclide conjugate 64Cu-Ab5-LP10 had high 64Cu enrichment (AUC1-72 h) in tumors and also had relatively long retention time. Example 41: Preparation of DLL3-Targeting Conjugates Ab12-LP10 and Ab9-LP5 Referring to the preparation method in Example 18, compound LP1 was separately replaced with compound LP10 and compound LP5, and single-domain antibody Ab62 was separately replaced with anti-DLL3 single-domain antibody Ab12 and scFv fragment Ab9 to prepare conjugates Ab12-LP10 and Ab9-LP5. The resulting conjugates were further purified and subjected to DAR tests. The DAR values and purity analysis (monomer ratio) results obtained are shown in the table below, wherein Ab9 was an scFv, and Ab12 was a VHH._____________ Conjugate No. DAR value Purity Ab12-LP10 0.78 98.53% Ab9-LP5 0.91 97.69% Example 42: Preparation of Radionuclide Conjugates 64Cu-Ab12-LP10 and 64Cu-Ab9-LP5 Referring to the preparation method in Example 28, conjugate Ab62-LP2 was separately replaced with the targeting conjugates Ab12-LP10 and Ab9-LP5 to prepare radionuclide conjugates 64Cu-Ab12-LP10 and 64Cu-Ab9-LP5, whose chemical purity and radiochemical purity determined by radio-HPLC after purification both met the requirements for subsequent tests. Example 43: Positron Emission Tomography (PET) Imaging Study of 64Cu-Labeled Radionuclide Conjugate in Tumor-Bearing Murine Model H82 with DLL3 Expression Radionuclide conjugate 64Cu-Ab12-LP10 was injected into H82 tumor-bearing murines with DLL3 expression. The tumor-bearing murines were then scanned at different time points using 5 PET / CT. The corresponding images and the amount of 64Cu in the tumor and key organ tissues were collected, and the ratios of 64Cu in the tumor to that in the blood and muscle were calculated. The results are shown in the table below: Ratios of 64Cu in tumor to that in blood and muscle 64Cu-Ab12-LP10 24h 48h Tumor / blood 1.8-2 2.0-3 Tumor / muscle 11.7-14 10.0-15 It can be seen that 64Cu-Ab12-LP10 can better enrich tumor sites.
Claims
1. A radionuclide conjugate, comprising a structure of formula (I) below:wherein0 formula (I)is a targeting moiety, and the remaining moiety is a payload unit, wherein the targetingmoietyand the payload unit form a covalent bond through enzymatic conjugation orchemical conjugation;each Q is independently an albumin-binding unit;each D is independently a chelating group for a radionuclide;La is a conjugating unit linking the targeting moiety and G, wherein each La isindependently selected from the following 1), 2), and a combination thereof:1) one or more natural or non-natural amino acids or oligomeric natural or non-natural amino acids with a degree of polymerization of 2-20;2) a chemical bond or C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -S-, -NH-, -(CO)-, C2-6 alkynyl, C3-10 cycloalkylene, 3- to 10-membered heterocycloalkylene, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, alkynyl, cycloalkylene, heterocycloalkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, sulfonyl-C1-10 alkyl, and 3- to 10-membered heterocycloalkyl;each Lb and each Lc, when present, is independently a chemical bond or C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -(CO)-, -NH-, -(C=S)-, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl;G is a branching moiety with a branching function, and is directly or indirectly linked to Q and D, wherein each G is independently selected from the following 3), 4), and a combination thereof:3) one or more natural or non-natural amino acids or oligomeric natural or non-natural amino acids with a degree of polymerization of 2-20;4) a chemical bond or C1-60 alkylene, wherein a carbon chain unit of the alkylene is optionallyreplaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl;j is an integer selected from 1 to 30;k is an integer selected from 1 to 20;o is an integer or non-integer greater than 0 and less than 20.
2. The radionuclide conjugate according to claim 1, whereinthe targeting moiety and the payload unit form a covalent bond through enzymaticconjugation;j is an integer selected from 1 to 10;k is an integer selected from 1 to 10;o is an integer or non-integer greater than 0 and less than 10.
3. A radionuclide conjugate, comprising a structure of formula (II) below:° formula (II)whereinis a targeting moiety, and the remaining moiety is a payload unit, wherein the targetingmoietyand the payload unit form a covalent bond through enzymatic conjugation orchemical conjugation;each Q is independently an albumin-binding unit; preferably, the albumin-binding unit is a small-molecule albumin-binding unit;each D is independently a chelating group for a radionuclide;each La is independently selected from the following 1), 2), and a combination thereof:1) a natural or non-natural amino acid or an oligomeric natural or non-natural amino acid with a degree of polymerization of 2-20;2) a chemical bond or C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -S-, -NH-, -(CO)-, C2-6 alkynyl, C3-10cycloalkylene, 3- to 10-membered heterocycloalkylene, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, alkynyl, cycloalkylene, heterocycloalkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, sulfonyl-C1-10 alkyl, and 3- to 10-membered heterocycloalkyl;each Lb and each Lc, when present, is independently a chemical bond or C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -(CO)-, -NH-, -(C=S)-, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl;each G1 or G3, when present, is independently selected from a chemical bond and C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; preferably, each G1 or G3, when present, is independently selected from a chemical bond, optionally substituted -NH-(C1-10 alkylene)-CO-, optionally substituted -NH-PEG-CO-, optionally substituted -NH-PEG-(C1-10 alkylene)-CO-, and optionally substituted -NH-(C1-10 alkylene)-PEG-CO-; the substituent for the substitution is selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl-; PEG is -(CH2CH2O)x- or -(OCH2CH2)y-, and x or y is an integer of 1-20;preferably,G1 and G3 are each independently selected from a chemical bond and the following structures:0 and 'each G2 or G4, when present, is independently a branching unit; preferably, each G2 or G4 is selected from one of or a combination of more of the following groups:1) one or more branched natural or non-natural amino acid fragments, wherein preferably, the branched natural or non-natural amino acid fragment has the following structure: -NH-(CR2R3)-CO-, wherein R2 and R3 are each independently selected from hydrogen, optionally substituted -(C1-10 alkylene)-NH-, and optionally substituted -(C1-10 alkylene)-CO-; R2 and R3 are not simultaneously hydrogen; more preferably, the branched natural or non-natural amino acid is a glutamic acid fragment, an aspartic acid fragment, or a lysine fragment; the substituent for the substitution is selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl-; 2) C1-20 linear or branched alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at leastone substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl;preferably, G2 and G4 are each independently combination thereof:the following structural fragment or aHN''N NOH H, ,wherein one terminus of the wavy line marked with * is a terminus proximal ton1 and n2 are each independently an integer of 0-10;j1, j2, k1, and k2 are each independently an integer of 0-10;o is an integer or non-integer greater than 0 and less than 10.
4. The radionuclide conjugate according to claim 3, whereinthe targeting moiety conjugation;and the payload unit form a covalent bond through enzymaticPEG is -(CH2CH2O)x- or -(OCH2CH2)y-, wherein x or y is an integer of 1-10;preferably,G1 and G3 are each independently selected from a chemical bond and the following structures:H i"^'OO'V Hn *%.no andpreferably, G2 and G4 are each independently the following structural fragment or a combination thereof:HN%o or H H , wherein one terminus of the wavy line marked with *\Ais a terminus proximal to5. The radionuclide conjugate according to any one of claims 1-4, whereinthe targeting moietyis selected from a ligand, a polypeptide, and an antibody or anantigen-binding fragment thereof that specifically bind to a target; preferably, the targetingmoietyis an antibody or an antigen-binding fragment thereof; more preferably, the\Atargeting moiety is selected from a single-domain antibody and a single-chain antibody.
6. The radionuclide conjugate according to any one of claims 1-5, wherein <%\the targeting moiety is an anti-prostate-specific membrane antigen (PSMA) antibody, ananti-epidermal growth factor receptor 2 (HER2) antibody, or an anti-Delta-like ligand 3 (DLL3) antibody.
7. The radionuclide conjugate according to claim 6, whereinthe targeting moietycomprises an HCDR1 set forth in SEQ ID NO: 1, an HCDR2 set forthin SEQ ID NO: 2, and an HCDR3 set forth in SEQ ID NO: 3; orthe targeting moietycomprises an HCDR1 set forth in SEQ ID NO: 4, an HCDR2 set forthin SEQ ID NO: 5, and an HCDR3 set forth in SEQ ID NO: 6; orthe targeting moietycomprises an HCDR1 set forth in SEQ ID NO: 7, an HCDR2 set forthin SEQ ID NO: 8, and an HCDR3 set forth in SEQ ID NO: 9; orthe targeting moietycomprises an HCDR1 set forth in SEQ ID NO: 23, an HCDR2 setforth in SEQ ID NO: 24, and an HCDR3 set forth in SEQ ID NO: 25.
8. The radionuclide conjugate according to claim 6, whereinthe targeting moietycomprises the amino acid sequence set forth in SEQ ID NO: 10 orSEQ ID NO: 11, or comprises the amino acid sequence set forth in positions 1 to 127 of SEQID NO: 12, or comprises the amino acid sequence set forth in positions 1 to 115 of SEQ ID NO:22; orthe targeting moiety comprises an amino acid sequence having at least 85% identity to theamino acid sequence set forth in SEQ ID NO: 10 or SEQ ID NO: 11, or comprises an amino acid sequence having at least 85% identity to the amino acid sequence set forth in positions 1 to 127 of SEQ ID NO: 12, or comprises an amino acid sequence having at least 85% identity to the amino acid sequence set forth in positions 1 to 115 of SEQ ID NO: 22.
9. The radionuclide conjugate according to any one of claims 1-4, whereinthe targeting moietyand the payload unit are conjugated by an enzyme, and the enzymeused in enzymatic conjugation is a ligase, wherein the ligase is selected from a Sortase enzyme, a transglutaminase, a formylglycine-generating enzyme, a tyrosinase, and an asparagine ligase;under the action of the ligase, the targeting moiety forms La of the payload unit throughreaction with La';preferably, the targeting moietycomprises a ligase recognition substrate, and La'comprises a ligase recognition substrate; preferably, the targeting moietycomprises aligase donor recognition substrate, and La' comprises a ligase acceptor recognition substrate;preferably, La' comprises a ligase donor recognition substrate, and the targeting moiety comprises a ligase acceptor recognition substrate.
10. The radionuclide conjugate according to claim 9, whereinthe targeting moietyand the payload unit form a covalent bond through enzymaticconjugation; under the action of the ligase, the targeting moiety forms La of the payloadunit through reactionwith La';the ligase is a Sortase enzyme, and the targeting moiety and La' comprise a recognitionsequence for a Sortase enzyme donor substrate or an acceptor substrate sequence, respectively; preferably, the recognition sequence for the donor substrate is LPX1TGX2, and the recognition sequence for the acceptor substrate is (Gly)n, wherein X1 is any natural or non-natural amino acid, X2 is absent or is an amino acid fragment comprising 1-10 amino acids, and n is an integer of 2-20; orthe ligase is a transglutaminase, and the targeting moiety and La' comprise a recognitionstructure for a transglutaminase donor substrate or a recognition structure for a transglutaminaseacceptor substrate, respectively; preferably, La' comprises -NH2, and the targeting moiety comprises glutamine; more preferably, La' comprises C1-10 alkylene-NH2 or lysine; orthe ligase is a formylglycine-generating enzyme, and the targeting moietyand La'comprise a recognition structure for a formylglycine-generating enzyme donor substrate or a recognition structure for a formylglycine-generating enzyme acceptor substrate, respectively;preferably, La' comprisesh ror h2n ? , wherein the wavy line represents a site of<Aattachment to G, G1, or G2 of the payload unit, and the targeting moietycomprisesrecognition sequence CX3PX4R, wherein X3 and X4 are any natural or non-natural amino acids; orthe ligase is a tyrosinase, and the targeting moiety and La' comprise a recognition structurefor a tyrosinase donor substrate or a recognition structure for a tyrosinase acceptor substrate,respectively; preferably, La' comprises a bicyclo[6.1.0]nonyne structure, and the targetingmoietycomprises tyrosine; orthe ligase is an asparagine ligase, and the targeting moietyand La' comprise a recognitionstructure for an asparagine ligase donor substrate or a recognition structure for an asparagineligase acceptor substrate, respectively; preferably, the asparagine ligase is Singzyme, La'comprises amino acid fragment GI, and the targeting moietycomprises recognitionsequence NX5L, wherein X5 is any natural or non-natural amino acid; or the asparagine ligaseis butelase, La' comprises amino acid fragment GI, and the targeting moietycomprisesrecognition sequence NHV.
11. The radionuclide conjugate according to any one of claims 1-4, whereineach La is independently selected from the following structures:-(Gly)n-, wherein n is an integer selected from 2 to 20, preferably an integer of 2-10, and more preferably 3;-NH-C1-10 alkylene-(CO)-, preferably -NH-(CH2)4-(CO)-.
12. The radionuclide conjugate according to claim 1 or 2, wherein each G is independently selected from the following structures:g , andwherein g is an integer selected from 1 to 20, preferably an integer of 1-5; further preferably,andwherein the wavy line marked with * represents a site of attachment to La, the wavy line marked with # represents a site of attachment to Lc or Lb, and the wavy line represents a site of attachment to Lb or Lc.
13. The radionuclide conjugate according to claim 3, whereinwhen n2 is 0, G2 and G3 are absent, and G4 is selected from the following structural fragments:when n2 is not 0, G2 and G4 are both the following structural fragment:wherein the wavy line marked with * represents a site of attachment to G1 or G3.
14. The radionuclide conjugate according to any one of claims 1-4, whereineach Lb is independently selected from the following structures:a chemical bond;, wherein the wavy line marked with * represents a site of attachment to D, andthe wavy line represents a site of attachment to G, G2, or G4;wherein the wavy line marked with * represents a site ofattachment to D, and the wavy line represents a site of attachment to G, G2, or G4; orwherein the wavy line marked with * represents a site ofattachment to D, and the wavy line represents a site of attachment to G, G2, or G4.
15. The radionuclide conjugate according to any one of claims 1-4, whereinLc is a chemical bond; or, wherein the wavy line marked with * represents a site of attachment to Q, andthe wavy line represents a site of attachment to G, G2, or G4.
16. The radionuclide conjugate according to any one of claims 1-4, whereinQ is a small-molecule binder; preferably, each Q is independently selected from the followingstructures:J / ; / H , , O , andwhereinR1 is selected from H, C1-6 alkyl, halogen, methoxy, and trifluoromethyl; preferably, R1 isselected from methyl and iodine;Ra1 to Ra11 are each independently selected from hydrogen, C1-6 alkyl, C1-6 alkoxy, halogen,cyano, nitro, amino, and hydroxyl;preferably, each Q is independentlyClselected from0and17. The radionuclide conjugate according to any one of claims 1-4, whereineach D is independently selected from:bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (CBTE2a), cyclohexyl-1,2-diaminetetraacetic acid (CDTA), 4-(1,4,8,11-tetraazacyclotetradec-1-yl)-methylbenzoic acid (CPTA), N'-[5-[acetyl(hydroxy)amino]pentyl]-N-[5-[[4-[5-aminopentyl-(hydroxy)amino]-4-oxobutanoyl]amino]pentyl]-N-hydroxybutanediamide (DFO), 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (DO2A),1,4,7,10-tetraazacyclododecane-N, N, N", N"'-tetraacetic acid (DOTA), a-(2-carboxyethyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTAGA), 1,4,7,10-azacyclododecane-N,N',N'',N'''-1,4,7,10-tetra(methylene)phosphonic acid (DOTMP), N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5''-bis(phosphate) (DPDP), diethylenetriamine-N,N',N''-penta(methylene)phosphonic acid (DTMP), diethylenetriaminepentaacetic acid (DTPA), ethylenediamine-N,N'-tetraacetic acid (EDTA), ethylene glycol-O,O-bis(2-aminoethyl)-N,N,N'',N''-tetraacetic acid (EGTA), N,N-bis(hydroxybenzyl)-ethylenediamine-N,N''-diacetic acid (HBED), hydroxyethylethylenediaminetriacetic acid (HEDTA), 1-(p-nitrobenzyl)-1,4,7,10-tetraazacyclodecane-4,7,10-triacetate (HP-DOA3), 6-hydrazinyl-N-methylpyridine-3-carboxamide (HYNIC), tetra 3-hydroxy-N-methyl-2-pyridone chelator abbreviated as Me-3,2-HOPO (4-((4-(3-(bis(2-(3-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamido)ethyl)amino)-2-((bis(2-(3-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamido)ethyl)amino)methyl)propyl)phenyl)amino)-4-oxobutanoic acid), 1,4,7-triazacyclononane-1-succinic acid-4,7-diacetic acid (NODASA), 1-(1-carboxy-3-carboxypropyl)-4,7-(carboxy)-1,4,7-triazacyclononane (NODAGA), 1,4,7-triazacyclononanetriacetic acid (NOTA), 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (TE2A), 1,4,8,11-tetraazacyclododecane-1,4,8,11-tetraacetic acid (TETA), tris(hydroxypyridone) (THP), terpyridine-bis(methyleneaminetetraacetic acid) (TMT), 1,4,7-triazacyclononane-1,4,7-tris[methylene(2-carboxyethyl)phosphinic acid] (TRAP), 1,4,7,10-tetraazacyclotridecane-N,N',N'',N'''-tetraacetic acid (TRITA), 3-[[4,7-bis[[2-carboxyethyl(hydroxy)phosphoryl]methyl]-1,4,7-triazacyclononan-1-yl]methyl-hydroxy-phosphoryl]propanoic acid, triethylenetetraminehexaacetic acid (TTHA), and N1-(5-aminopentyl)-N1-hydroxy-N4-(5-(N-hydroxy-4-((5-(N-hydroxyacetamido)pentyl)amino)-4-oxobutanamido)pentyl)butanediamide;preferably,each D is independently selected from 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, 1,4,7-triazacyclononanetriacetic acid (NOTA), and N1-(5-aminopentyl)-N1-hydroxy-N4-(5-(N-hydroxy-4-((5-(N-hydroxyacetamido)pentyl)amino)-4-oxobutanamido)pentyl)butanediamide.
18. The radionuclide conjugate according to any one of claims 1-4, whereinthe radionuclide is selected from any radioactive cation or anion of F, Br, I, Sc, Cu, Ga, Y, In, Lu, Tc, Sm, Sr, Ra, Tb, Ho, Re, Pb, Bi, Ac, Th, Co, Gd, Dy, Zr, At, and Er;preferably,the radionuclide is selected from 18F, 77Br, 131I, 125I, 43Sc, 44Sc, 47Sc, 64Cu, 67Cu, 67Ga, 68Ga, 86Y, 90Y, 90In, 111In, 177Lu, 94Tc, 99Tc, 153Sm, 89Sr, 223Ra, 151Tb, 166Ho, 186Re, 188Re, 212Pb, 213Bi, 212Bi, 225Ac, 227Th, 55Co, 57Co, 152Gd, 153Gd, 157Gd, 166Dy, 89Zr, and 211At;more preferably,the radionuclide is selected from 68Ga, 64Cu, and 177Lu.
19. The radionuclide conjugate according to claim 1, whereinthe radionuclide conjugate comprises a structure selected from the following: / 1 Hud „ HN- A H 0 H 0 0 NH' H U H H hm^0NH' < a n y N n A \l H S h S 0 5 / 1 H 9 H H H 0 H O 0 I HOOC—y--1 / - N Nx % NX HOOC— 9 a xy H || H ?IH ? <A —n "ArN n "ArN '^'o'^v n 'TfN x / 3'~x'A AT H n H n H n H X / dy1 1 H >—\ / --\ / — co2h k a 3 £ o A M HO2C—co2h XjO"1 0 —\ / --\ / — COOH H NN ^N N^ HOOC—1 f COOH VAX' 0 [ -AAx H 4 NH 0 -COOH a xy' r 0 1 --y--COOH rT N n N ° H c HOOC—! --1 '—COOH / 1 H ? H \r h g h q 5 0 NH^^ / 1 H n H A.Mk < -n^n^n^n^o^°^o^>X^hn Jf n H n no 5 h ^1 h || H ^"1 H 0 H 0 0 ^1 H H HN- << O 0 9 <K / LPET. H 9 H J \aX Xy^'^ H O " s s HOOC—\y--yy—COOH N N NH o X N^ \ COOH 1 HN HN'>X>—N n o ) o / HN V—\ / --\ / ~COOH O N N. ^N N^ HOOC—'--1 '—COOH -J N^( / 1 / Z \ 0H CT) o^N'-^ N'°H > X HN -^0 0 Xo S S H0'N N N -^^)- N N H H \= / H H x xy1 HO2C^ / V C°2H S \__|\|__ / _O / I H H \= / C°2H ^~^y' 1 H >—i / --1 / —CO2H s C—; ^N N^ ho2c—co2h HOOC—\ / --^COOH « » o ^N N >—7 \-- / ^COOH HN X h2n so3h J HO )=( 'Y^yxX'XMo H 0 / \hooc^ ^cooh , andHOOC^ - / ^COOH,wherein -S- and -GA-LPET- in the structure described above are portions of the amino acidscomprised in the targeting moiety20. The radionuclide conjugate according to any one of claims 1-4, comprising a structure offormula (I') below:whereinformula (I')Q is an albumin-binding unit;D and D' are each independently a chelating group for a radionuclide;A is a single-domain antibody or a single-chain antibody, or an antigen-binding fragment thereof;Ld is selected from a chemical bond and C1-60 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-; L1, L2, L1', and L2' are each independently a chemical bond or an amino acid fragment with a degree of polymerization of 1-10, or selected from one or a combination of the following divalent groups: C1-10 alkylene, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, nitro, cyano, and C1-10 alkyl;m is an integer selected from 0 to 20;n is an integer selected from 2 to 20;z is an integer selected from 1 to 20.
21. The radionuclide conjugate according to claim 20, whereina terminus of A is modified to be conjugated with (Gly)n in formula (I') under the action of a ligase.
22. The radionuclide conjugate according to claim 21, wherein the ligase is a Sortase enzyme; and / orA comprises an antibody with a C-terminal modification, wherein an antibody, a spacer (SP), and a recognition sequence for a ligase donor substrate are sequentially linked, or an antibody and a recognition sequence for a ligase donor substrate are sequentially linked; and / or SP is selected from GA, GGGGS, GGGGSGGGGS, and GGGGSGGGGSGGGGS; and / or the recognition sequence for a ligase donor substrate is LPX1TGX2, wherein X1 is any natural or non-natural amino acid, and X2 is absent or is an amino acid fragment comprising 1-10 amino acids.
23. The radionuclide conjugate according to any one of claims 20-22, whereinLd is selected from a chemical bond, -NH-C1-20 alkylene-(CO)-, and -NH-(PEG)i-(CO)-, wherein (PEG)i comprises 1-20 structural units selected from -(O-C2H4)- and -(C2H4-O)-, and is optionally linked to C1-10 alkylene at at least one terminus of the -(O-C2H4)- or -(C2H4-O)-structural unit.
24. The radionuclide conjugate according to any one of claims 20-22, whereinLd is -NH-(PEG)i-(CO)-, wherein (PEG)i is 1-20 consecutive -(O-C2H4)- or -(C2H4-O)-structural units, and is optionally linked to C1-10 alkylene at at least one terminus of the -(O-C2H4)- or -(C2H4-O)- structural unit;preferably, Ld is -NH-(PEG)i-C1-10 alkylene-(CO)-;more preferably, Ld is -NH-PEG4-C2H4-(CO)-; further preferably, Ld is -NH-(C2H4-O)4-C2H4-(CO)-.
25. The radionuclide conjugate according to any one of claims 20-22, whereinL1 and L1' are each independently selected from any one of a chemical bond, C1-10 alkylene, -NH-, and -(CO)-, or any combination thereof;preferably, L1 is selected from -(CH2)4-NH-, -CO-NH-C2H4-NH-, and -NH-;preferably, L1' is selected from a chemical bond, -(CH2)4-NH-, -CO-NH-C2H4-NH-, and -NH-.
26. The radionuclide conjugate according to any one of claims 20-22, whereinL2 and L2' are each independently selected from any one of a chemical bond, an amino acid fragment with a degree of polymerization of 1-10, -(CO)-, C1-10 alkylene, and -NH-, or any combination thereof;preferably, L2 is selected from -(CO)-, -(CH2)4-NH-, -CO-amino acid fragment with degree of polymerization of 1-10-, and -CO-Lys-;preferably, L2' is selected from a chemical bond, -(CO)-, -(CH2)4-NH-, -CO-amino acid fragment with degree of polymerization of 1-10-, and -CO-Lys-.
27. The radionuclide conjugate according to any one of claims 20-22, wherein m is an integer selected from 0 to 10; preferably, m is 0, 1, or 2, more preferably 0 or 1; n is an integer selected from 2 to 10; preferably, n is 2, 3, or 4; more preferably, n is 3; and / orwhen Ld is -NH-(PEG)i-C1-10 alkylene-(CO)-, i is an integer selected from 1 to 12; preferably, i is 2, 3, 4, 5, or 6; more preferably, i is 4;and / orz is an integer selected from 1 to 10; preferably, z is 1, 2, 3, or 4; more preferably, z is 1.
28. The radionuclide conjugate according to any one of claims 20-22, wherein D and D' are each independently selected from bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (CBTE2a), cyclohexyl-1,2-diaminetetraacetic acid (CDTA), 4-(1,4,8,11-tetraazacyclotetradec-1-yl)-methylbenzoic acid (CPTA), N'-[5-[acetyl(hydroxy)amino]pentyl]-N-[5-[[4-[5-aminopentyl-(hydroxy)amino]-4-oxobutano yl]amino]pentyl]-N-hydroxybutanediamide (DFO), 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (DO2A), 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA), a-(2-carboxyethyl)-1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid (DOTAGA), 1,4,7,10-azacyclododecane-N,N',N'',N'''-1,4,7,10-tetra(methylene)phosphonic acid (DOTMP), N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5''-bis(phosphate) (DPDP), diethylenetriamine-N,N',N''-penta(methylene)phosphonic acid (DTMP), diethylenetriaminepentaacetic acid (DTPA), ethylenediamine-N,N'-tetraacetic acid (EDTA), ethylene glycol-O,O-bis(2-aminoethyl)-N,N,N'',N''-tetraacetic acid (EGTA), N,N-bis(hydroxybenzyl)-ethylenediamine-N,N''-diacetic acid (HBED), hydroxyethylethylenediaminetriacetic acid (HEDTA), 1-(p-nitrobenzyl)-1,4,7,10-tetraazacyclodecane-4,7,10-triacetate (HP-DOA3), 6-hydrazinyl-N-methylpyridine-3-carboxamide (HYNIC), tetra 3-hydroxy-N-methyl-2-pyridone chelator abbreviated as Me-3,2-HOPO(4-((4-(3-(bis(2-(3-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamido)ethyl)amino )-2-((bis(2-(3-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamido)ethyl)amino)met hyl)propyl)phenyl)amino)-4-oxobutanoic acid), 1,4,7-triazacyclononane-1-succinic acid-4,7-diacetic acid (NODASA),1-(1-carboxy-3-carboxypropyl)-4,7-(carboxy)-1,4,7-triazacyclononane (NODAGA), 1,4,7-triazacyclononanetriacetic acid (NOTA),4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (TE2A), 1,4,8,11-tetraazacyclododecane-1,4,8,11-tetraacetic acid (TETA), tris(hydroxypyridone) (THP), terpyridine-bis(methyleneaminetetraacetic acid) (TMT), 1,4,7-triazacyclononane-1,4,7-tris[methylene(2-carboxyethyl)phosphinic acid] (TRAP), 1,4,7,10-tetraazacyclotridecane-N,N',N'',N'''-tetraacetic acid (TRITA), 3-[[4,7-bis[[2-carboxyethyl(hydroxy)phosphoryl]methyl]-1,4,7-triazacyclononan-1-yl]methyl -hydroxy-phosphoryl]propanoic acid, and triethylenetetraminehexaacetic acid (TTHA);preferably,D is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid;D' is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid.
29. The radionuclide conjugate according to any one of claims 20-22, whereinthe radionuclide is selected from any radioactive cation or anion of F, Br, I, Sc, Cu, Ga, Y, In, Lu, Tc, Sm, Sr, Ra, Tb, Ho, Re, Pb, Bi, Ac, Th, Co, Gd, Dy, Zr, At, and Er;preferably,the radionuclide is selected from 18F, 77Br, 131I, 125I, 43Sc, 44Sc, 47Sc, 64Cu, 67Cu, 67Ga, 68Ga, 86Y, 90Y, 90In, 111In, 177Lu, 94Tc, 99Tc, 153Sm, 89Sr, 223Ra, 151Tb, 166Ho, 186Re, 188Re, 212Pb, 213Bi, 212Bi, 225Ac, 227Th, 55Co, 57Co, 152Gd, 153Gd, 157Gd, 166Dy, 89Zr, and 211At.
30. The radionuclide conjugate according to any one of claims 20-22, whereinQ is selected from:whereinR1 is selected from H, C1-6 alkyl, halogen, methoxy, and trifluoromethyl; preferably, R1 is selected from methyl and iodine;Ra1 to Ra11 are each independently selected from hydrogen, C1-6 alkyl, C1-6 alkoxy, halogen, cyano, nitro, amino, and hydroxyl;31. The radionuclide conjugate according to any one of claims 20-22, whereinA is an anti-prostate-specific membrane antigen (PSMA) antibody, an anti-epidermal growth factor receptor 2 (HER2) antibody, or an anti-Delta-like ligand 3 (DLL3) antibody.
32. A compound, comprising a structure of formula (III) below:jk formula (III)whereineach Q is independently an albumin-binding unit;each D is independently a chelating group for a radionuclide;La' is selected from the following 1), 2), and a combination thereof:1) one or more natural or non-natural amino acids or oligomeric natural or non-natural amino acids with a degree of polymerization of 2-20;2) C1-20 alkyl, wherein a carbon chain unit of the alkyl is optionally replaced with at least one substituent selected from -O-, -S-, -NH-, -(CO)-, C2-6 alkynyl, C3-10 cycloalkylene, 3- to 10membered heterocycloalkylene, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, alkynyl, cycloalkylene, heterocycloalkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, sulfonyl-C1-10 alkyl, and 3- to 10-membered heterocycloalkyl;each Lb and each Lc, when present, is independently a chemical bond or C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -(CO)-, -NH-, -(C=S)-, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl;G is a branching moiety with a branching function, and is directly or indirectly linked to Q and D, wherein each G is independently selected from the following 3), 4), and a combination thereof:3) one or more natural or non-natural amino acids or oligomeric natural or non-natural amino acids with a degree of polymerization of 2-20;4) a chemical bond or C1-60 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10alkyl;j is an integer selected from 1 to 30;k is an integer selected from 1 to 20.
33. A compound, comprising a structure of formula (IV) below:whereineach Q is independently an albumin-binding unit; preferably, the albumin-binding unit is a small-molecule albumin-binding unit;each D is independently a chelating group for a radionuclide;each La' is independently selected from the following 1), 2), and a combination thereof:1) a natural or non-natural amino acid or an oligomeric natural or non-natural amino acid with a degree of polymerization of 2-20;2) C1-20 alkyl, wherein a carbon chain unit of the alkyl is optionally replaced with at least one substituent selected from -O-, -S-, -NH-, -(CO)-, C2-6 alkynyl, C3-10 cycloalkylene, 3- to 10membered heterocycloalkylene, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, alkynyl, cycloalkylene, heterocycloalkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, sulfonyl-C1-10 alkyl, and 3- to 10-membered heterocycloalkyl;each Lb and each Lc, when present, is independently a chemical bond or C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -(CO)-, -NH-, -(C=S)-, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl;each G1 or G3, when present, is independently selected from a chemical bond and C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; preferably, each G1 or G3, when present, is independently selected from a chemical bond, optionally substituted -NH-(C1-10 alkylene)-CO-, optionally substituted -NH-PEG-CO-, optionally substituted -NH-PEG-(C1-10 alkylene)-CO-, and optionally substituted -NH-(C1-10 alkylene)-PEG-CO-; the substituent for the substitution is selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl-; PEG is -(CH2CH2O)x- or -(OCH2CH2)y-, and x or y is an integer of 1-20;preferably,G1 and G3 are each independently selected from a chemical bond and the following structures:0'y hII *s.N0 andeach G2 or G4, when present, is independently a branching unit; preferably, each G2 or G4 is selected from one of or a combination of more of the following groups:1) one or more branched natural or non-natural amino acid fragments, wherein preferably, the branched natural or non-natural amino acid fragment has the following structure: -NH-(CR2R3)-CO-, wherein R2 and R3 are each independently selected from hydrogen, optionally substituted -(C1-10 alkylene)-NH-, and optionally substituted -(C1-10 alkylene)-CO-; R2 and R3 are not simultaneously hydrogen; more preferably, the branched natural or non-natural amino acid is a glutamic acid fragment, an aspartic acid fragment, or a lysine fragment; the substituent for the substitution is selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl-; 2) C1-20 linear or branched alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl;preferably, G2 and G4 are each independently combination thereof:HNH I — <----N4--N A %OH H, ,the following structural fragment or a0 , and0 ■;wherein one terminus of the wavy line marked with * is a terminus proximal to La'; n1 and n2 are each independently an integer of 0-10;j1, j2, k1, and k2 are each independently an integer of 0-10.
34. The compound according to claim 32 or 33, wherein La' is selected from the following structures:(Gly)n, wherein n is an integer selected from 2 to 20, preferably an integer of 2-10, and more preferably 3;C1-10 alkyl-(CO)-, wherein the alkyl is substituted with a substituent of amino; preferably NH2-(CH2)4-(CO)-.
35. The compound according to claim 32, wherein G is selected from the following structures:9 , andwherein g is an integer selected from 1 to 20, preferably an integer of 1-5;further preferably,HNHN,andHN / ,wherein the wavy line marked with * represents a site of attachment to La', the wavy line markedwith # represents a site of attachment to Lc, and the wavy line represents a site of attachment to Lb.
36. The compound according to claim 33, whereinwhen n2 is 0, G2 and G3 are absent, and G4 is selected from the following structural fragments:when n2 is not 0, G2 and G4 are both the following structural fragment:wherein the wavy line marked with * represents a site of attachment to G1 or G3.
37. The compound according to claim 32 or 33, whereineach Lb is independently selected from the following structures:a chemical bond;, wherein the wavy line marked with * represents a site of attachment to D, andthe wavy line represents a site of attachment to G, G2, or G4;H S SH H \= / H , wherein the wavy line marked with * represents a site ofattachment to D, and the wavy line represents a site of attachment to G, G2, or G4; orH H \= / , wherein the wavy line marked with * represents a site ofattachment to D, and the wavy line represents a site of attachment to G, G2, or G4.
38. The compound according to claim 32 or 33, whereinLc is a chemical bond; or, wherein the wavy line marked with * represents a site of attachment to Q, andthe wavy line represents a site of attachment to G, G2, or G4.
39. The compound according to claim 32 or 33, whereinQ is a small-molecule binder; preferably, each Q is independently selected from the followingstructures:andwhereinR1 is selected from H, C1-6 alkyl, halogen, methoxy, and trifluoromethyl; preferably, R1 isselected from methyl and iodine;Ra1 to Ra11 are each independently selected from hydrogen, C1-6 alkyl, C1-6 alkoxy, halogen,cyano, nitro, amino, and hydroxyl;preferably, Q is selected from40. The compound according to claim 32 or 33, wherein each D is independently selected from:bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (CBTE2a), cyclohexyl-1,2-diaminetetraacetic acid (CDTA), 4-(1,4,8,11-tetraazacyclotetradec-1-yl)-methylbenzoic acid (CPTA), N'-[5-[acetyl(hydroxy)amino]pentyl]-N-[5-[[4-[5-aminopentyl-(hydroxy)amino]-4-oxobutanoyl]amino]pentyl]-N-hydroxybutanediamide (DFO), 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (DO2A),1,4,7,10-tetraazacyclododecane-N, N, N",N"’-tetraacetic acid (DOTA), a-(2-carboxyethyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTAGA), 1,4,7,10-azacyclododecane-N,N',N'',N'''-1,4,7,10-tetra(methylene)phosphonic acid (DOTMP), N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5''-bis(phosphate) (DPDP), diethylenetriamine-N,N',N''-penta(methylene)phosphonic acid (DTMP), diethylenetriaminepentaacetic acid (DTPA), ethylenediamine-N,N'-tetraacetic acid (EDTA), ethylene glycol-O,O-bis(2-aminoethyl)-N,N,N'',N''-tetraacetic acid (EGTA), N,N-bis(hydroxybenzyl)-ethylenediamine-N,N''-diacetic acid (HBED), hydroxyethylethylenediaminetriacetic acid (HEDTA), 1-(p-nitrobenzyl)-1,4,7,10-tetraazacyclodecane-4,7,10-triacetate (HP-DOA3), 6-hydrazinyl-N-methylpyridine-3-carboxamide (HYNIC), tetra 3-hydroxy-N-methyl-2-pyridone chelator abbreviated as Me-3,2-HOPO (4-((4-(3-(bis(2-(3-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamido)ethyl)amino)-2-((bis(2-(3-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamido)ethyl)amino)methyl)propyl)phenyl)amino)-4-oxobutanoic acid), 1,4,7-triazacyclononane-1-succinic acid-4,7-diacetic acid (NODASA), 1-(1-carboxy-3-carboxypropyl)-4,7-(carboxy)-1,4,7-triazacyclononane (NODAGA), 1,4,7-triazacyclononanetriacetic acid (NOTA), 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (TE2A), 1,4,8,11-tetraazacyclododecane-1,4,8,11-tetraacetic acid (TETA), tris(hydroxypyridone) (THP), terpyridine-bis(methyleneaminetetraacetic acid) (TMT), 1,4,7-triazacyclononane-1,4,7-tris[methylene(2-carboxyethyl)phosphinic acid] (TRAP), 1,4,7,10-tetraazacyclotridecane-N,N',N'',N'''-tetraacetic acid (TRITA), 3-[[4,7-bis[[2-carboxyethyl(hydroxy)phosphoryl]methyl]-1,4,7-triazacyclononan-1-yl]methyl-hydroxy-phosphoryl]propanoic acid, triethylenetetraminehexaacetic acid (TTHA), and N1-(5-aminopentyl)-N1-hydroxy-N4-(5-(N-hydroxy-4-((5-(N-hydroxyacetamido)pentyl)amino)-4-oxobutanamido)pentyl)butanediamide;preferably,each D is independently selected from 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, 1,4,7-triazacyclononanetriacetic acid (NOTA), and N1-(5-aminopentyl)-N1-hydroxy-N4-(5-(N-hydroxy-4-((5-(N-hydroxyacetamido)pentyl)amino)-4-oxobutanamido)pentyl)butanediamide.
41. The compound according to claim 32 or 33, whereinthe radionuclide is selected from any radioactive cation or anion of F, Br, I, Sc, Cu, Ga, Y, In, Lu, Tc, Sm, Sr, Ra, Tb, Ho, Re, Pb, Bi, Ac, Th, Co, Gd, Dy, Zr, At, and Er;preferably,the radionuclide is selected from 18F, 77Br, 131I, 125I, 43Sc, 44Sc, 47Sc, 64Cu, 67Cu, 67Ga, 68Ga, 86Y, 90Y, 90In, 111In, 177Lu, 94Tc, 99Tc, 153Sm, 89Sr, 223Ra, 151Tb, 166Ho, 186Re, 188Re, 212Pb, 213Bi, 212Bi, 225Ac, 227Th, 55Co, 57Co, 152Gd, 153Gd, 157Gd, 166Dy, 89Zr, and 211At;more preferably,the radionuclide is selected from 68Ga, 64Cu, and 177Lu.
42. The compound according to claim 32 or 33, wherein the compound is selected from:ClHO2C—co2handhooc^^^cooh , andHOOC—! ^COOH.
43. A compound, comprising a structure of formula (II'):whereinformula (II'),Q is an albumin-binding unit;D and D' are each independently a chelating group for a radionuclide;Ld is selected from a chemical bond and C1-60 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-; L1, L2, and each L1' and L2' are each independently a chemical bond or an amino acid fragment with a degree of polymerization of 1-10, or selected from one or a combination of the following divalent groups: C1-10 alkylene, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, nitro, cyano, and C1-10 alkyl;m is an integer selected from 0 to 20;n is an integer selected from 2 to 20.
44. The compound according to claim 43, whereinLd is selected from a chemical bond, -NH-C1-20 alkylene-(CO)-, and -NH-(PEG)i-(CO)-, wherein (PEG)i comprises 1-20 structural units selected from -(O-C2H4)- and -(C2H4-O)-, and is optionally linked to C1-10 alkylene at at least one terminus of the -(O-C2H4)- or -(C2H4-O)-structural unit.
45. The compound according to claim 44, whereinLd is -NH-(PEG)i-(CO)-, wherein (PEG)i is 1-20 consecutive -(O-C2H4)- or -(C2H4-O)-structural units, and is optionally linked to C1-10 alkylene at at least one terminus of the -(O-C2H4)- or -(C2H4-O)- structural unit;preferably, Ld is -NH-(PEG)i-C1-10 alkylene-(CO)-;preferably, Ld is -NH-PEG4-C2H4-(CO)-; more preferably, Ld is -NH-(C2H4-O)4-C2H4-(CO)-.
46. The compound according to any one of claims 43-45, whereinL1 and L1' are each independently selected from any one of a chemical bond, C1-10 alkylene, -NH-, and -(CO)-, or any combination thereof;preferably, L1 is selected from -(CH2)4-NH-, -CO-NH-C2H4-NH-, and -NH-;preferably, L1' is selected from a chemical bond, -(CH2)4-NH-, -CO-NH-C2H4-NH-, and -NH-.
47. The compound according to any one of claims 43-45, whereinL2 and L2' are each independently selected from any one of a chemical bond, an amino acid fragment with a degree of polymerization of 1-10, -(CO)-, C1-10 alkylene, and -NH-, or any combination thereof;preferably, L2 is selected from -(CO)-, -(CH2)4-NH-, -CO-amino acid fragment with degree of polymerization of 1-10-, and -CO-Lys-;preferably, L2' is selected from a chemical bond, -(CO)-, -(CH2)4-NH-, -CO-amino acid fragment with degree of polymerization of 1-10-, and -CO-Lys-.
48. The compound according to any one of claims 43-45, whereinm is an integer selected from 0 to 10; preferably, m is 0, 1, or 2; more preferably, m is 0 or 1; n is an integer selected from 2 to 10; preferably, n is 2, 3, or 4; more preferably, n is 3;and / orwhen Ld is -NH-(PEG)i-C1-10 alkylene-(CO)-, i is an integer selected from 1 to 12; preferably, i is 2, 3, 4, 5, or 6; more preferably, i is 4.
49. The compound according to any one of claims 43-45, whereinD and D' are each independently selected from bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (CBTE2a), cyclohexyl-1,2-diaminetetraacetic acid (CDTA), 4-(1,4,8,11-tetraazacyclotetradec-1-yl)-methylbenzoic acid (CPTA), N'-[5-[acetyl(hydroxy)amino]pentyl]-N-[5-[[4-[5-aminopentyl-(hydroxy)amino]-4-oxobutano yl]amino]pentyl]-N-hydroxybutanediamide (DFO), 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (DO2A),1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA), a-(2-carboxyethyl)-1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid (DOTAGA), 1,4,7,10-azacyclododecane-N,N',N'',N'''-1,4,7,10-tetra(methylene)phosphonic acid (DOTMP), N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5''-bis(phosphate) (DPDP), diethylenetriamine-N,N',N''-penta(methylene)phosphonic acid (DTMP), diethylenetriaminepentaacetic acid (DTPA), ethylenediamine-N,N'-tetraacetic acid (EDTA), ethylene glycol-O,O-bis(2-aminoethyl)-N,N,N'',N''-tetraacetic acid (EGTA), N,N-bis(hydroxybenzyl)-ethylenediamine-N,N''-diacetic acid (HBED), hydroxyethylethylenediaminetriacetic acid (HEDTA), 1-(p-nitrobenzyl)-1,4,7,10-tetraazacyclodecane-4,7,10-triacetate (HP-DOA3), 6-hydrazinyl-N-methylpyridine-3-carboxamide (HYNIC), tetra 3-hydroxy-N-methyl-2-pyridone chelator abbreviated as Me-3,2-HOPO (4-((4-(3-(bis(2-(3-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamido)ethyl)amino )-2-((bis(2-(3-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamido)ethyl)amino)met hyl)propyl)phenyl)amino)-4-oxobutanoic acid), 1,4,7-triazacyclononane-1-succinic acid-4,7-diacetic acid (NODASA), 1-(1-carboxy-3-carboxypropyl)-4,7-(carboxy)-1,4,7-triazacyclononane (NODAGA), 1,4,7-triazacyclononanetriacetic acid (NOTA), 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (TE2A), 1,4,8,11-tetraazacyclododecane-1,4,8,11-tetraacetic acid (TETA), tris(hydroxypyridone) (THP), terpyridine-bis(methyleneaminetetraacetic acid) (TMT), 1,4,7-triazacyclononane-1,4,7-tris[methylene(2-carboxyethyl)phosphinic acid] (TRAP), 1,4,7,10-tetraazacyclotridecane-N,N',N'',N'''-tetraacetic acid (TRITA), 3-[[4,7-bis[[2-carboxyethyl(hydroxy)phosphoryl]methyl]-1,4,7-triazacyclononan-1-yl]methyl -hydroxy-phosphoryl]propanoic acid, and triethylenetetraminehexaacetic acid (TTHA); preferably,D is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid;D' is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid.
50. The compound according to any one of claims 43-45, wherein the radionuclide is selected from any radioactive cation or anion of F, Br, I, Sc, Cu, Ga, Y, In, Lu, Tc, Sm, Sr, Ra, Tb, Ho, Re, Pb, Bi, Ac, Th, Co, Gd, Dy, Zr, At, and Er; preferably,the radionuclide is selected from 18F, 77Br, 131I, 125I, 43Sc, 44Sc, 47Sc, 64Cu, 67Cu, 67Ga, 68Ga, 86Y, 90Y, 90In, 111In, 177Lu, 94Tc, 99Tc, 153Sm, 89Sr, 223Ra, 151Tb, 166Ho, 186Re, 188Re, 212Pb, 213Bi, 212Bi, 225Ac, 227Th, 55Co, 57Co, 152Gd, 153Gd, 157Gd, 166Dy, 89Zr, and 211At, and preferably 68Ga, 64Cu, and 177Lu.
51. The compound according to any one of claims 43-45, wherein Q is selected from:whereinR1 is selected from H, C1-6 alkyl, halogen, methoxy, and trifluoromethyl; preferably, R1 is selected from methyl and iodine;Ra1 to Ra11 are each independently selected from hydrogen, C1-6 alkyl, C1-6 alkoxy, halogen,cyano, nitro, amino, and hydroxyl;52. A radionuclide conjugate, comprising a structure of formula (V) below:k formula (V)whereineach Lb is covalently linked to a chelating group, and each Lc is covalently linked to an albuminbinding unit;each Lb and each Lc, when present, is independently a chemical bond or C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -(CO)-, -NH-, -(C=S)-, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl;G is a branching moiety with a branching function, wherein G is selected from the following 1), 2), and a combination thereof:1) one or more natural or non-natural amino acids or oligomeric natural or non-natural amino acids with a degree of polymerization of 2-20;2) a chemical bond or C1-60 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl;j is an integer selected from 1 to 30;k is an integer selected from 1 to 20.
53. A radionuclide conjugate, comprising a structure of formula (VI) below:whereinformula (VI)each Lb is covalently linked to a chelating group, and each Lc is covalently linked to an albuminbinding unit;each Lb and each Lc, when present, is independently a chemical bond or C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -(CO)-, -NH-, -(C=S)-, C6-10 arylene, and 5- to 10-membered heteroarylene, wherein the alkylene, arylene, and heteroarylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl;each G1 or G3, when present, is independently selected from a chemical bond and C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl; preferably, each G1 or G3, when present, is independently selected from a chemical bond, optionally substituted -NH-(C1-10 alkylene)-CO-, optionally substituted -NH-PEG-CO-, optionally substituted -NH-PEG-(C1-10 alkylene)-CO-, and optionally substituted -NH-(C1-10 alkylene)-PEG-CO-; the substituent for the substitution is selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl,C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl-; PEG is -(CH2CH2O)x- or -(OCH2CH2)y-, and x or y is an integer of 1-20;preferably,G1 and G3 are each independently selected from a chemical bond and the following structures:0;each G2 or G4, when present, is independently a branching unit; preferably, each G2 or G4 isselected from one of or a combination of more of the following groups:1) one or more branched natural or non-natural amino acid fragments, wherein preferably, the branched natural or non-natural amino acid fragment has the following structure: -NH-(CR2R3)-CO-, wherein R2 and R3 are each independently selected from hydrogen, optionally substituted -(C1-10 alkylene)-NH-, and optionally substituted -(C1-10 alkylene)-CO-; R2 and R3 are not simultaneously hydrogen; more preferably, the branched natural or non-natural amino acid is a glutamic acid fragment, an aspartic acid fragment, or a lysine fragment; the substituent for the substitution is selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl-; 2) C1-20 linear or branched alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl;preferably, G2 and G4 are each independently the following structural fragment or a combination thereof:hn% y,*s H C° * H [*i s i 1 “?—-1—nA yH—n- / . / -. ,n / \ \ rPn n n ii iio , H H , O , and O ;wherein one terminus of the wavy line marked with * is a terminus proximal to G1;n1 and n2 are each independently an integer of 0-10;j1, j2, k1, and k2 are each independently an integer of 0-10.
54. The radionuclide conjugate according to claim 52, wherein G is selected from the following structures:9 , andwherein g is an integer selected from 1 to 20, preferably an integer of 1-5; further preferably,andwherein the wavy line marked with # represents a site of attachment to Lc or Lb, and the wavy line represents a site of attachment to Lb or Lc.
55. The radionuclide conjugate according to claim 53, whereinwhen n2 is 0, G2 is absent, and G4 is selected from the following structural fragments:when n2 is not 0, G2 and G4 are both the following structural fragment:wherein the wavy line marked with * represents a site of attachment to G1 or G3.
56. The radionuclide conjugate according to claim 52 or 53, wherein each Lb is independently selected from the following structures: a chemical bond;h , wherein the wavy line marked with * represents a site of attachment to thechelating group, and the wavy line represents a site of attachment to G, G2, or G4;H H \= / H , wherein the wavy line marked with * represents a site ofattachment to the chelating group, and the wavy line represents a site of attachment to G, G2, or G4; orn^n—\ 7—H H \== / , wherein the wavy line marked with * represents a site ofattachment to the chelating group, and the wavy line represents a site of attachment to G, G2, or G4.
57. The radionuclide conjugate according to claim 52 or 53, whereinLc is a chemical bond; orh , wherein the wavy line marked with * represents a site of attachment to thealbumin-binding unit, and the wavy line represents a site of attachment to G, G2, or G4.
58. A radionuclide conjugate, comprising a structure of formula (III') below:formula (III'),whereinLd is selected from a chemical bond and C1-60 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-; L1, L2, and each L1' and L2' are each independently covalently linked to a chelating group or an albumin-binding unit; L1, L2, and each L1' and L2' are each independently a chemical bond or an amino acid fragment with a degree of polymerization of 1-10, or selected from one or acombination of the following divalent groups: C1-10 alkylene, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, nitro, cyano, and C1-10 alkyl;m is an integer selected from 0 to 20.
59. The radionuclide conjugate according to claim 58, whereinLd is selected from a chemical bond, -NH-C1-20 alkylene-(CO)-, and -NH-(PEG)i-(CO)-, wherein (PEG)i comprises 1-20 structural units selected from -(O-C2H4)- and -(C2H4-O)-, and is optionally linked to C1-10 alkylene at at least one terminus of the -(O-C2H4)- or -(C2H4-O)-structural unit.
60. The radionuclide conjugate according to claim 58, whereinLd is -NH-(PEG)i-(CO)-, wherein (PEG)i is 1-20 consecutive -(O-C2H4)- or -(C2H4-O)-structural units, and is optionally linked to C1-10 alkylene at at least one terminus of the -(O-C2H4)- or -(C2H4-O)- structural unit;preferably, Ld is -NH-(PEG)i-C1-10 alkylene-(CO)-;preferably, Ld is -NH-PEG4-C2H4-(CO)-; more preferably, Ld is -NH-(C2H4-O)4-C2H4-(CO)-.
61. The radionuclide conjugate according to any one of claims 58-60, whereinL1 and L1' are each independently selected from any one of a chemical bond, C1-10 alkylene, -NH-, and -(CO)-, or any combination thereof;preferably, L1 is selected from -(CH2)4-NH-, -CO-NH-C2H4-NH-, and -NH-;preferably, L1' is selected from a chemical bond, -(CH2)4-NH-, -CO-NH-C2H4-NH-, and -NH-.
62. The radionuclide conjugate according to any one of claims 58-60, whereinL2 and L2' are each independently selected from any one of a chemical bond, an amino acid fragment with a degree of polymerization of 1-10, -(CO)-, C1-10 alkylene, and -NH-, or any combination thereof;preferably, L2 is selected from -(CO)-, -(CH2)4-NH-, -CO-an amino acid fragment with a degree of polymerization of 1-10-, and -CO-Lys-; preferably, L2 is -CO-Lys-;preferably, L2' is selected from a chemical bond, -(CO)-, -(CH2)4-NH-, -CO-an amino acid fragment with a degree of polymerization of 1-10-, and -CO-Lys-; preferably, L2' is -CO-Lys-.
63. The radionuclide conjugate according to any one of claims 58-60, whereinm is an integer selected from 0 to 10; preferably, m is 0, 1, or 2, more preferably 0 or 1;n is an integer selected from 2 to 10; preferably, n is 2, 3, or 4; more preferably, n is 3; and / orwhen Ld is -NH-(PEG)i-C1-10 alkylene-(CO)-, i is an integer selected from 1 to 12; preferably,i is 2, 3, 4, 5, or 6; more preferably, i is 4.
64. A radionuclide conjugate, comprising a structure of formula (VII) below:whereinformula (VII)Ld' is selected from C1-20 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-;RA and RB are each independently optionally linked to a chelating group and / or an albuminbinding unit; RA and RB are each independently selected from hydrogen and one or a combination of the following groups: C1-10 alkylene, -NH-, and -(CO)-, wherein the alkylene is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, nitro, cyano, and C1-10 alkyl; RA and RB are not simultaneously hydrogen;RC is optionally covalently linked to a chelating group, an albumin-binding unit, or a combination thereof; RC is selected from one or a combination of the following: hydroxyl, a natural or non-natural amino acid fragment, and C1-30 alkylene, wherein a carbon chain unit of the alkylene is optionally replaced with at least one substituent selected from -O-, -NR4-, -(CO)-, -(C=S)-, and C6-10 arylene, and the alkylene and arylene are optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl;R4 is selected from hydrogen and C1-10 alkyl, wherein a carbon chain unit of the alkyl is optionally replaced with at least one substituent selected from -O-, -NH-, and -(CO)-, and the alkyl is optionally substituted with at least one substituent selected from hydroxyl, halogen, amino, sulfhydryl, nitro, cyano, sulfonyl, C1-10 alkyl, C1-10 alkoxy, amine group, and sulfonyl-C1-10 alkyl.
65. The radionuclide conjugate according to claim 64, whereinLd' is selected from -(PEG)i- and C1-10 alkylene, wherein (PEG)i is 1-10 consecutive -(O-C2H4)-or -(C2H4-O)- structural units, and is optionally linked to C1-10 alkylene at at least one terminus of the -(O-C2H4)- or -(C2H4-O)- structural unit;preferably, Ld' is selected from -(C2H4-O)4-C2H4- and C5 alkylene.
66. The radionuclide conjugate according to claim 64, whereinRA and RB are each independently selected from hydrogen and C1-10 alkylene, wherein the alkylene is substituted with at least one substituent selected from hydroxyl, halogen, amino, nitro, cyano, and C1-10 alkyl; RA and RB are not simultaneously hydrogen;preferably, RA and RB are each independently hydrogen or C1-10 alkylene, wherein the alkyleneis substituted with amino; RA and RB are not simultaneously hydrogen;more preferably, RA and RB are each independently hydrogen or67. The radionuclide conjugate according to claim 64, whereinRC is selected from hydroxyl,, and68. The radionuclide conjugate according to claim 64, whereinHN^HN^HhA HlAHN^HNNHHNOS S, andpreferably,and69. Use of the radionuclide conjugate according to any one of claims 1-31, the compound according to any one of claims 32-51, or the radionuclide conjugate according to any one of claims 52-68 in the preparation of a radionuclide conjugate.
70. A radionuclide conjugate, comprising a radionuclide and the radionuclide conjugate according to any one of claims 1-31 or 52-68 or the compound according to any one of claims 32-51.
71. A pharmaceutical composition, comprising the radionuclide conjugate according to claim 70, and optionally at least one pharmaceutically acceptable carrier.
72. Use of the radionuclide conjugate according to any one of claims 1-31 or 52-68 or 70 or the pharmaceutical composition according to claim 71 for medical treatment and / or diagnosis.
73. Use of the radionuclide conjugate according to any one of claims 1-31 or 52-68 or 70 or the pharmaceutical composition according to claim 71 in the preparation of a therapeutic radiopharmaceutical or a diagnostic radiopharmaceutical,wherein the therapeutic radiopharmaceutical or the diagnostic radiopharmaceutical is used for treating or diagnosing malignant lymphoma, testicular seminoma, Wilms tumor, neuroblastoma, medulloblastoma, Ewing’s sarcoma, small cell lung cancer, head and neck squamous cellcarcinoma, esophageal squamous cell carcinoma, lung squamous cell carcinoma, breast cancer, cervical cancer, skin cancer, gastrointestinal adenocarcinoma, pancreatic cancer, prostate cancer, fibrosarcoma, liposarcoma, or rhabdomyosarcoma.
74. A method for diagnosing, delaying, or treating a disease, comprising administering to a subject in need thereof an effective amount of the radionuclide conjugate according to any one of claims 1-31 or 52-68 or 70 or the pharmaceutical composition according to claim 71, wherein the disease comprises malignant lymphoma, testicular seminoma, Wilms tumor, neuroblastoma, medulloblastoma, Ewing’s sarcoma, small cell lung cancer, head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, lung squamous cell carcinoma, breast cancer, cervical cancer, skin cancer, gastrointestinal adenocarcinoma, pancreatic cancer, prostate cancer, fibrosarcoma, liposarcoma, or rhabdomyosarcoma.
