Conjugate comprising peptide and payload

Abstract

[Problem] To provide: a conjugate of a peptide having CLDN18.2 binding activity and a payload; and others. [Solution] A conjugate comprising a peptide such as peptide A2 (ddab-Tbg-F4CON-Gthp-Y3Me-HeG-4Py-N-mCPeG-Cba-P-D-C (SEQ ID NO: 136)) and a payload, wherein the payload comprises a chelating agent and / or a radioactive isotope; and others.

Description

Conjugate containing peptide and payload 【0001】 This invention relates to a conjugate comprising a peptide and a payload (sometimes also referred to as a "peptide conjugate," "peptide complex," or simply "conjugate"), and to the use of said conjugate. 【0002】CLDN18.2 (Claudin18.2) is a 27.8 kDa four-transmembrane protein that constitutes tight junctions (TJs) between gastric mucosal epithelial cells (Genbank accession numbers NM_001002026, NP_001002026). Gastric mucosal epithelial cells tightly adhere to each other through the formation of TJs, adhesion junctions, and desmosomes at the base of the cell, forming a barrier function that prevents microorganisms and foreign substances from entering the body. It is also known to be involved in intercellular proton transport. Two isoforms of Claudin are known, 18.1 and 18.2. 18.1 is expressed in normal alveolar epithelial cells, while it is hardly or never expressed in gastric mucosal epithelial cells. On the other hand, CLDN18.2 is prominently expressed in normal gastric mucosal epithelial cells. Under physiological conditions, CLDN18.2 forms homodimers between cells. Although the involvement of CLDN18.2 in gastric cancer formation is not clear, it is thought that the breakdown of tight junctions (TJs) and loss of polarity in gastric cancer cells suppress differentiation and contribute to gastric cancer formation through increased invasiveness and abnormal cell proliferation. Due to these changes, the expression of CLDN18.2 in gastric cancer cells shifts from TJs to the cell surface. This change in the expression pattern of CLDN18.2 provides a basis for the therapeutic application of anti-CLDN18.2 antibodies, such as zolbetuximab, which binds to the first extracellular loop of CLDN18.2, in gastric cancer. Two Phase 3 clinical trials of zolbetuximab for CLDN18.2-positive gastric cancer have been completed, reporting statistically significant improvement effects, and it has been approved as a drug. The efficacy of zolbetuximab has been found to correlate with a high expression rate of CLDN18.2 in gastric cancer cells. CLDN18.2 is a promising target for gastric cancer treatment, and many clinical trials are underway for antibody therapy using ADCC and CDC, T-cell engagement therapy using bispecific antibodies that bind to CD3 and CLDN18.2, and CAR-T-cell therapy involving the introduction of CAR genes consisting of CLDN18.2 and various immune signaling molecules such as 4-1BB and CD28.Furthermore, ectopic expression of CLDN18.2 has been reported not only in gastric cancer but also in pancreatic ductal cancer and malignant progenitor lesions of the ovary, suggesting that, like gastric cancer, it may be a potential therapeutic target in the future. 【0003】 Izuma Nakayama, et al. Nat. Rev. Clin. Oncol. 2024 May; 21(5):354-369. 【0004】 The present inventors have diligently conducted research with the aim of creating a conjugate in which a peptide having CLDN18.2 binding activity is bound to a payload, and as a result, have conceived the present invention. The present invention relates to a conjugate of a novel peptide having CLDN18.2 binding activity and a payload containing a radioisotope and / or a chelating agent, a composition containing the conjugate (pharmaceutical composition, diagnostic composition, research composition), and the use of the conjugate. 【0005】Non-limitingly, this application includes the following inventions: [1] A conjugate comprising peptide A and a payload, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof (hereinafter these will also be collectively referred to simply as "conjugate"), wherein peptide A comprises an amino acid sequence represented by formula A1, or an amino acid sequence in which one or more amino acid residues are substituted, deleted, added or inserted in the amino acid sequence represented by formula A1, A1: X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13, where, in peptide A, X1 is an arbitrary D-amino acid residue, X2 is an arbitrary amino acid residue, X3 is an amino acid residue having an optionally substituted aryl group in its side chain, X4 is an arbitrary amino acid residue, X5 is an amino acid residue having an optionally substituted aryl group in its side chain, and X6 is an optionally N-alkylated glycine residue (alkyl may have substituents), X7 is any amino acid residue, X8 is N, X9 is an N-alkylated glycine residue (the alkyl group may have a substituted or aryl group), X10 is an amino acid residue having an aliphatic hydrocarbon group in its side chain, X11 is a 4-6 membered cyclic secondary amino acid residue, X12 is D, X13 is a peptide wherein (1) C or aMeC, or (2) A or G, and furthermore, G, MeG, Medn, Meda, dp, or Meds is added to the C-terminus of X13 as the 14th amino acid residue (X14), and the payload comprises a radioisotope and / or a chelating agent. 【0006】[2] The peptide A is such that in formula A1, X1 is da, dhgl, dp, ds, df4COO, dn, ddab, dk, dyae, dkCopipzaa, dd, dorn, or ddap, X2 is S, 4Py, Cha, Tbg, W7N, F4aao, K, Yae, or IMe, X3 is 3Py6NH2, F4CON, F4OMe, F4Me, or Y, and X4 is Y, F4C, F4F, 3Py6NHaa, Atp, V, Cha, 5Pyrm, F4aao, Tbg, Gthp, Cbg, YaeAc, Yae, or YaeCopipzaa, X5 is 3Py6NH2, Y, or Y3Me, X6 is MeG, HeG, CmG, PeG, AcaeG, CmpG, CmmG, MeopG, or AcapG, X7 is S, 4Py, Nmm, Ndm, HseMe, Hse, 4Pyz1Me, 3Py5CON, 4Py3CON, 3Py6pipz4Ac, K, Yae, YaeCOPipzaa, 3Py6O4thp, F4CON, 3Py6O4pip1Ac, 3Py6CON, 3Py6mor, or 4Pyz, X8 is N, X9 is PeG, mCPeG, or oCPeG, X10 is L or Cba, The conjugate according to [1], wherein X11 is P or Hpr and X12 is D. 【0007】[3] The conjugate according to [1] wherein peptide A comprises an amino acid sequence represented by formula A2, or an amino acid sequence in which 1 to 11 amino acid residues arbitrarily selected from the group consisting of the 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 9th, 10th, 11th, and 13th amino acid residues from the N-terminus of the amino acid sequence represented by formula A2 are substituted or deleted. A2: ddab-Tbg-F4CON-Gthp-Y3Me-HeG-4Py-N-mCPeG-Cba-P-D-C (SEQ ID NO: 136) [4] The conjugate according to any one of [1] to [3] wherein peptide A comprises a peptide having the amino acid sequence of SEQ ID NOs: 1 to 179. [5] The conjugate according to any one of [1] to [4] wherein peptide A further comprises additional amino acid residues. [6] The conjugate according to any one of [1] to [5], wherein peptide A is a cyclic peptide. [7] The conjugate according to any one of [1] to [6], wherein peptide A is a peptide having a cyclic structure in which the first amino acid residue of the amino acid sequence contained in peptide A is chloroacetylated, and the chloroacetylated amino acid residue is intramolecularly bonded to C or aMeC contained in the same peptide A. [8] The conjugate according to any one of [1] to [6], wherein peptide A is a peptide having a cyclic structure in which the amino group of the first amino acid residue of the amino acid sequence contained in peptide A is bonded to the carboxyl group of the C-terminal amino acid residue of peptide A. [9] The conjugate according to any one of [1] to [8], wherein (i) the payload is bound to the C-terminus of peptide A, with or without a linker, or (ii) the payload is bound to the 1st, 2nd, 4th, or 7th amino acid residue of the amino acid sequence represented by formula A1 of peptide A, with or without a linker.

[10] The conjugate according to any one of [1] to [9], wherein the payload contains the radioactive isotope.

[11] The conjugate according to

[10] , wherein the payload contains the radioactive isotope bound to the chelating agent.

[12] The conjugate according to any one of [1] to [9], wherein the payload contains the chelating agent and does not contain the radioisotope. 【0008】

[13] A pharmaceutical composition comprising the conjugate described in

[10] or

[11] .

[14] A pharmaceutical composition comprising the conjugate described in

[10] or

[11] for the prevention or treatment of Claudin 18.2-related disease.

[15] A diagnostic or research composition comprising the conjugate described in

[10] or

[11] .

[16] A diagnostic or research composition comprising the conjugate described in

[10] or

[11] for the diagnosis of Claudin 18.2-related disease. 【0009】

[17] An imaging agent comprising the conjugate described in

[10] or

[11] .

[18] An imaging agent used for tumor diagnosis comprising the conjugate described in

[10] or

[11] . 【0010】

[19] A method for testing a conjugate, wherein the conjugate is a conjugate described in any one of the following: a) solubility in a solvent; b) Claudin 18.2 binding activity; c) toxicity to cells and / or tissues; or d) toxicity to experimental animals. 【0011】

[20] A conjugate comprising peptide B and a payload, wherein peptide B comprises an amino acid sequence represented by formula B1, or an amino acid sequence in which one or more amino acid residues are substituted, deleted, added or inserted in the amino acid sequence represented by formula B1. B1: Y1-Y2-Y3-Y4-Y5-Y6-Y7-Y8-Y9-Y10-Y11-Y12-Y13 where, Y1 is any D-amino acid residue, Y2 is an amino acid residue having an optionally substituted aryl group in its side chain, Y3 is any amino acid residue, Y4 is an amino acid residue having an optionally substituted aryl group in its side chain, Y5 is an optionally N-alkylated glycine residue (the alkyl group may have substituents), Y6 is an amino acid residue having an optionally substituted aryl group in its side chain, Y7 is N, Y8 is an optionally N-alkylated glycine residue (the alkyl group may have an optionally substituted aryl group), Y9 is an amino acid residue having an aliphatic hydrocarbon group in its side chain, Y10 is P, Y11 is D Y12 is an amino acid residue having an optionally substituted aryl group in its side chain, Y13 is a peptide having (1) C or aMeC, or (2) N or bA2SMe, further having MeG or MeS added as the 14th amino acid residue (Y14) to the C-terminus of Y13, and the payload comprises a radioisotope and / or a chelating agent, the conjugate. 【0012】

[21] The peptide B is such that in formula B1, Y1 is da, dp, dk, dp4SNH2, dorn, or dkAc, Y2 is 3Py6NH2, F4OMe, 3Py6Me, 3Py6Et, or Y, Y3 is Y, N, Tbg, Yae, YaeAc, or Gthp, Y4 is Y or Y3Me, Y5 is MeG, EtG, HeG, or AcaeG, Y6 is 4Py, 3Py6OMe, 3Py, or 3Py6CON, Y7 is N, Y8 is PeG, mCPeG, or 3FPeG, Y9 is L or Cba, Y10 is P, and Y11 is D. The conjugate according to

[20] , wherein Y12 is 3Py6NH2, 4Py, Y3Me, YaeCopipzaa, Yae, YaeAc, or F3CON.

[22] The conjugate according to

[20] , wherein peptide B comprises an amino acid sequence represented by formula B2, or an amino acid sequence in which 1 to 9 amino acid residues arbitrarily selected from the group consisting of the 1st, 2nd, 3rd, 4th, 5th, 6th, 8th, 9th, and 12th amino acid residues from the N-terminus are substituted or deleted. B2: dp4SNH2-3Py6Me-Gthp-Y3Me-HeG-4Py-N-mCPeG-Cba-P-D-YaeCopipzaa-C (SEQ ID NO: 215)

[23] The conjugate according to any one of

[20] to

[22] , wherein peptide B comprises a peptide having the amino acid sequence of SEQ ID NOs: 180 to 223.

[24] The conjugate according to any one of

[20] to

[23] , wherein peptide B further comprises an additional amino acid residue.

[25] The conjugate according to any one of

[20] to

[24] , wherein peptide B is a cyclic peptide.

[26] The conjugate according to

[25] , wherein peptide B is a peptide having a cyclic structure in which the first amino acid residue of the amino acid sequence contained in peptide B is chloroacetylated, and the chloroacetylated amino acid residue is intramolecularly bonded to C or aMeC contained in the same peptide B.

[27] The conjugate according to

[25] , wherein the peptide B is a peptide having a cyclic structure in which the amino group of the first amino acid residue of the amino acid sequence contained in the peptide B is bonded to the carboxyl group of the C-terminal amino acid residue of the peptide B.

[28] The conjugate according to any one of

[20] to

[27] , wherein (i) the payload is bonded to the C-terminus of the peptide B with or without a linker, or (ii) the payload is bonded to the first, third, or twelfth amino acid residue of the amino acid sequence contained in the peptide B with or without a linker.

[29] The conjugate according to any one of

[20] to

[28] , wherein the payload contains the radioactive isotope.

[30] The conjugate according to

[29] , wherein the payload contains the radioactive isotope bonded to the chelating agent.

[31] The conjugate according to any one of

[20] to

[28] , wherein the payload contains the chelating agent and does not contain the radioisotope. 【0013】

[32] A pharmaceutical composition comprising the conjugate described in

[29] or

[30] .

[33] A pharmaceutical composition comprising the conjugate described in

[29] or

[30] for the prevention or treatment of Claudin 18.2-related disease.

[34] A diagnostic or research composition comprising the conjugate described in

[29] or

[30] .

[35] A diagnostic or research composition comprising the conjugate described in

[29] or

[30] for the diagnosis of Claudin 18.2-related disease. 【0014】

[36] An imaging agent comprising the conjugate described in

[29] or

[30] .

[37] An imaging agent used for tumor diagnosis comprising the conjugate described in

[29] or

[30] . 【0015】

[38] A method for testing a conjugate, wherein the conjugate is a conjugate described in any one of the following: a) solubility in a solvent; b) Claudin 18.2 binding activity; c) toxicity to cells and / or tissues; or d) toxicity to experimental animals. 【0016】 The peptide conjugate according to the present invention has CLDN18.2 binding activity and is therefore useful as a pharmaceutical composition, diagnostic composition, and research composition for the prevention or treatment of CLDN18.2-related symptoms. 【0017】 Figure 1 shows the peptide conjugate (structure number 135) of the present invention. １７７ This graph shows the in vivo distribution of the Lu-labeled peptide conjugate in HT-29-hCLDN18.2 tumor-bearing mice at 1, 4, and 24 hours after administration. The horizontal axis represents each tissue, and the vertical axis represents the radioactivity concentration (%ID / g) in each tissue. Figure 2 shows the peptide conjugate (structure number 136) of the present invention. １７７ This graph shows the in vivo distribution of the Lu-labeled peptide conjugate in HT-29-hCLDN18.2 tumor-bearing mice at 1, 4, and 24 hours after administration. The horizontal axis represents each tissue, and the vertical axis represents the radioactivity concentration (%ID / g) in each tissue. Figure 3 shows the peptide conjugate (structure number 170) of the present invention. １７７ This graph shows the in vivo distribution of the Lu-labeled peptide conjugate in HT-29-hCLDN18.2 tumor-bearing mice at 1, 4, and 24 hours after administration. The horizontal axis represents each tissue, and the vertical axis represents the radioactivity concentration (%ID / g) in each tissue. Figure 4 shows the peptide conjugate (structure number 171) of the present invention. １７７ This graph shows the in vivo distribution results of HT-29-hCLDN18.2 tumor-bearing mice 1, 4, and 24 hours after administration of Lu-labeled peptide conjugates. The horizontal axis represents each tissue, and the vertical axis represents the radioactivity concentration (%ID / g) in each tissue. Figure 5 shows the peptide conjugates of the present invention (structure numbers 135, 136, 170, 171) ６４Representative PET / CT images of HT-29-hCLDN18.2 tumor-bearing mice at 2, 4, 24, and 47.5 hours after administration of the peptide conjugate labeled with Cu. The white arrows in the figure indicate the location of the transplanted tumors. Figure 6 shows the １７７ Graph showing the change in average tumor volume in BxPC3-hCLDN18.2 tumor-bearing mice administered with the peptide conjugate labeled with Lu, physiological saline, or gemcitabine. The horizontal axis represents the number of days after administration, and the vertical axis represents the tumor volume (mm ３ ). Also, the solid black circle line represents physiological saline, the dashed gray circle line represents gemcitabine, the solid unfilled circle line represents １７７ Lu-labeled peptide conjugate (structural number 135) (single administration), the solid black triangle line represents １７７ Lu-labeled peptide conjugate (structural number 135) (three administrations), the dashed gray triangle line represents １７７ Lu-labeled peptide conjugate (structural number 136) (single administration), the solid unfilled triangle line represents １７７ Lu-labeled peptide conjugate (structural number 136) (three administrations), the solid black square line represents １７７ Lu-labeled peptide conjugate (structural number 170) (single administration), the solid unfilled square line represents １７７ Lu-labeled peptide conjugate (structural number 170) (three administrations), the solid black diamond line represents １７７ Lu-labeled peptide conjugate (structural number 171) (single administration), the solid unfilled diamond square line represents １７７ Lu-labeled peptide conjugate (structural number 171) (three administrations). Figure 7 shows the １７７ Graph showing the change in average body weight in BxPC3-hCLDN18.2 tumor-bearing mice administered with the peptide conjugate labeled with Lu, physiological saline, or gemcitabine. The horizontal axis represents the number of days after administration, and the vertical axis represents the body weight change rate (%). Also, the solid black circle line represents physiological saline, the dashed gray circle line represents gemcitabine, the solid unfilled circle line represents １７７ Lu-labeled peptide conjugate (structural number 135) (single administration), the solid black triangle line represents １７７Lu-labeled peptide conjugate (structure number 135) (3 doses), gray dashed triangle is １７７ Lu-labeled peptide conjugate (structure number 136) (single dose), the hollow triangle solid line is １７７ Lu-labeled peptide conjugate (structure number 136) (3 doses), the solid black square is １７７ Lu-labeled peptide conjugate (structure number 170) (single dose), the solid line in the hollow square is １７７ Lu-labeled peptide conjugate (structure number 170) (3 doses), the black diamond solid line is １７７ Lu-labeled peptide conjugate (structure number 171) (single dose), hollow diamond-shaped solid line is １７７ Figure 8 (left) shows the Lu-labeled peptide conjugate (structure number 171) (3 doses). Figure 8 (left) shows the peptide conjugate of the present invention (structure number 136). ２２５ This graph (mean ± standard error) shows the change in mean tumor volume in BxPC3-hCLDN18.2 tumor-bearing mice administered with Ac-labeled peptide conjugate or physiological saline. The horizontal axis represents the number of days before and after administration, and the vertical axis represents the tumor volume (mm²). ３ ) indicates the base, and the solid black square indicates the base. ２２５ Ac-labeled peptide conjugate (structure number 136) (30 kBq), the black triangle solid line is ２２５ Ac-labeled peptide conjugate (structure number 136) (60 kBq), the black inverted triangle solid line is ２２５ The Ac-labeled peptide conjugate (structure number 136) (120 kBq) is shown. Figure 8 (right) shows the results of Dunnett's multiple comparison test using the average tumor volume values ​​35 days after administration (**: p < 0.01, ***: p < 0.001). Figure 9 (left) shows the peptide conjugate (structure number 136) of the present invention... ２２５ This graph shows the changes in average body weight in BxPC3-hCLDN18.2 tumor-bearing mice administered with Ac-labeled peptide conjugate or physiological saline. The horizontal axis represents the number of days after administration, and the vertical axis represents average body weight (g). The solid black circle line represents physiological saline, and the solid black square line represents ２２５ Ac-labeled peptide conjugate (structure number 136) (30 kBq), the black triangle solid line is ２２５Ac-labeled peptide conjugate (structure number 136) (60 kBq), the black inverted triangle solid line is ２２５ The Ac-labeled peptide conjugate (structure number 136) (120 kBq) is shown. Figure 9 (right) shows the results of Tukey's multiple comparison test using the average body weight 35 days after administration (ns: not signature). 【0018】 The present invention includes, but is not limited to, the following embodiments. Unless otherwise specified herein, the technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art. The substances, materials and examples disclosed herein are illustrative and not intended to limit them. Where the phrase "in one embodiment" is used herein, it means that the invention is not limited to that embodiment, i.e., it is not limited to that embodiment. 【0019】 1. Abbreviations In this specification, unless otherwise specified, the following abbreviations are used with the meanings set forth below. Abbreviations (General) Å: Angstrom (unit); ClAc: Chloroacetyl; Cy5SAlk: Sulfo-Cy5-alkyne; DCM: Dichloromethane; TIPS: Triisopropylsilyl; tert: Tertiary; DTT: Dithiothreitol; DMSO: Dimethyl sulfoxide; Trt: Trityl; Boc: Tertiary butoxycarbonyl; DMF: N,N-Dimethylformamide; DIEA or DIPEA: N,N-Diisopropylethylamine; DIPCI or DIC: N,N'-Diisopropylcarbodiimide; Oxyma pure: Cyano(hydroxyimino)ethyl acetate; DODT: 3,6-Dioxa-1,8-Octane-dithiol; DOTA-NHS ester: 2,2',2''-(10-(2-((2,5-dioxopyrrolidine-1-yl)oxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid; DOTA: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; Fmoc: 9-fluorenylmethyloxycarbonyl; g: grams (unit); H ２O: Water; HCl: Hydrogen chloride; HATU: O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; HOSu: N-hydroxysuccinimide; HPLC: High-performance liquid chromatography; LC-MS or LC / MS: Liquid chromatography-mass spectrometry; MeOH: Methanol; mL: Milliliter; M: Molar; μL: Microliter; mM: Millimol; μM: Micromolar; mmol: Millimole; mg: Milligram; MeCN or CH3CN: Acetonitrile; min: Minute; mm: Millimeter; μm: Micrometer; nm: Nanometer; nM: Nanomolar; NMP: N-methyl-2-pyrrolidone OSu: succinimide; PEG: polyethylene glycol; rpm: revolutions per minute (unit); tBu: tert-butyl; TFA: trifluoroacetic acid; TIS: triisopropylsilane; Trt or Tr: trityl group; H-PEG4Me: 2,5,8,11-tetraoxatridecane-13-amine; H-PEG8Me: 2,5,8,11,14,17,20,23-octaoxapentacosan-25-amine; AA: amino acid; PyAOP: 7-(azabenzotriazole-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate; Fmoc-OSu: N-(9-fluorenylmethoxycarbonyloxy)succinimide; THF: tetrahydrofuran; ClAcOSu: N-(chloroacetoxy)succinimide; EDCI・HCl: 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; Pd(PPh3)4: tetrakis(triphenylphosphine)palladium(0); ClAcOH: chloroacetic acid; conc: concentration; HFIP: 1,1,1,3,3,3-hexafluoro-2-propanol; Pbf: 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl; Alloc: allyloxycarbonyl; Allyl: allyl; apa: 1,3-propanediamine;aba: 1,4-butanediamine. 【0020】 Abbreviations (Non-natural amino acids, etc.) The abbreviations for non-natural amino acids in Table 1 below include those in which the amino group of the main chain is protected by common protecting groups such as Boc groups and Fmoc groups. 【0021】 2. Conjugates The present invention relates to a complex (also referred to as "peptide conjugate," "peptide complex," or simply "conjugate") comprising the peptide described in section 3 below (hereinafter also referred to as "peptide relating to the conjugate of the present invention") and the payload described in section 4 below (hereinafter also referred to as "payload relating to the conjugate of the present invention"), or a pharmaceutically acceptable salt thereof. The peptide in the conjugate includes all forms (including salts, isomers, solvates, etc.) as described in the section "3. Peptides" below. When referring to "peptide conjugate," "conjugate," or "peptide complex" in this specification, unless otherwise inconsistent, it also includes a pharmaceutically acceptable salt, isomer, or solvate thereof. 【0022】 In one embodiment, the conjugate of the present invention represents a complex in which a peptide related to the conjugate of the present invention and a payload related to the conjugate of the present invention are bound together, with or without the linker. In one embodiment, the conjugate of the present invention has the payload related to the conjugate of the present invention bound to the C-terminus of an amino acid residue contained in the peptide related to the conjugate of the present invention, with or without the linker. 【0023】In one embodiment, the conjugate of the present invention has a payload associated with the conjugate of the present invention bound to the side chain of an amino acid residue contained in the peptide associated with the conjugate of the present invention, with or without a linker. In one embodiment, the conjugate of the present invention has a payload bound to the 1st, 2nd, 4th, or 7th amino acid residue of SEQ ID NO: 136 contained in peptide A, with or without a linker. In one embodiment, the conjugate of the present invention has a payload bound to the 1st, 3rd, or 12th amino acid residue of SEQ ID NO: 215 contained in peptide B, with or without a linker. Not limited to, in the present invention, a conjugate includes the conjugates shown in Structure No. 42-179 and 182-223, and also includes conjugates in which the payload contained in those conjugates is substituted with a different payload. A conjugate with a different payload may be, for example, a conjugate in which the payloads DOTA, DOTALu, SulfoCy5, DOTAZr, SulfoCy5-PEG8c, DOTACu, DOTAGA, dDOTAGA, rNOTAGA, DOTA-#Ga, DOTALa in Structure No. 42-179 and 182-223 shown in Table 7 have been replaced with a different payload. 【0024】 For example, in the conjugate described in Structure No. 42, the payload sulfoCy5 bonded to the linker G-PEG10c-K may be a conjugate in which a chelating agent such as DOTA is further bonded to a chelating agent such as DOTA. Also, for example, in the conjugate described in Structure No. 135, the payload chelating agent DOTA bonded via the linker dk may be a conjugate in which a radioactive isotope is further bonded to the payload. For example, in the conjugate described in Structure No. 48, the payload chelating agent DOTA bonded via the linker dk may have a radioactive isotope instead of Lu (non-radioactive lutetium). １７７ It may also be a conjugate with Lu coupled to it. 【0025】 3. Peptides The peptides relating to the conjugates of the present invention relate to peptides or pharmaceutically acceptable salts thereof. When "peptide" is referred to herein, unless otherwise inconsistent, it also refers to pharmaceutically acceptable salts, isomers, or solvates thereof. A first embodiment of the peptide relating to the conjugates of the present invention (peptide A) is a peptide comprising an amino acid sequence represented by formula A1, or an amino acid sequence in which one or more amino acid residues are substituted, deleted, added, or inserted in the amino acid sequence represented by formula A1. In the peptide, the amino acid sequence is described from the N-terminus to the C-terminus in formula A1. 【0026】 Formula A1: X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13 In Formula A1, X1 is any D-amino acid residue, X2 is any amino acid residue, X3 is an amino acid residue having an optionally substituted aryl group in its side chain, X4 is any amino acid residue, X5 is an amino acid residue having an optionally substituted aryl group in its side chain, X6 is an optionally N-alkylated glycine residue (the alkyl group may have substituents), X7 is any amino acid residue, X8 is N, X9 is an optionally N-alkylated glycine residue (the alkyl group may have an optionally substituted aryl group), X10 is an amino acid residue having an aliphatic hydrocarbon group in its side chain, X11 is a 4-6 membered cyclic secondary amino acid residue, X12 is D X13 is (1) C or aMeC, or (2) A or G, and furthermore, G, MeG, Medn, Meda, dp, or Meds is added to the C-terminus of X13 as the 14th amino acid residue (X14). 【0027】Peptide A: In one embodiment, the peptide relating to the conjugate of the present invention includes the following amino acid sequence: ddab-Tbg-F4CON-Gthp-Y3Me-HeG-4Py-N-mCPeG-Cba-P-D-C (SEQ ID NO: 136) or an amino acid sequence having substitutions, additions, deletions or insertions in 1 to 11 amino acid residues arbitrarily selected from the group consisting of the 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 9th, 10th, 11th, and 13th amino acid residues of the above amino acid sequence. 【0028】 The amino acid sequence of Sequence ID No. 136 may have substitutions, additions, deletions, or insertions at 1 to 11 amino acid residues, which are arbitrarily selected from the group consisting of the 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 9th, 10th, 11th, and 13th amino acid residues. The number of substituted, deleted, added, and / or inserted amino acids may be between 1 and 11, with a lower limit of 1. The upper limit is 11, 10, 9, 8, 7, 6, 5, 4, 3, and 2, with a minimum of 1. 【0029】A second embodiment (peptide B) of the second embodiment of the peptide relating to the conjugate of the present invention is a peptide comprising an amino acid sequence represented by formula B1, or an amino acid sequence in which one or more amino acid residues are substituted, deleted, added, or inserted in the amino acid sequence represented by formula B1. Furthermore, in formula B1, the amino acid sequence of the peptide is described from the N-terminus to the C-terminus. Formula B1: Y1-Y2-Y3-Y4-Y5-Y6-Y7-Y8-Y9-Y10-Y11-Y12-Y13 In Formula B1, Y1 is any D-amino acid residue, Y2 is an amino acid residue having an optionally substituted aryl group in its side chain, Y3 is any amino acid residue, Y4 is an amino acid residue having an optionally substituted aryl group in its side chain, Y5 is an optionally N-alkylated glycine residue (the alkyl group may have substituents), Y6 is an amino acid residue having an optionally substituted aryl group in its side chain, Y7 is N, Y8 is an optionally N-alkylated glycine residue (the alkyl group may have an optionally substituted aryl group), Y9 is an amino acid residue having an aliphatic hydrocarbon group in its side chain, Y10 is P, Y11 is D Y12 is an amino acid residue having an optionally substituted aryl group in its side chain, Y13 is (1) C or aMeC, or (2) N or bA2SMe, and furthermore, MeG or MeS is added to the C-terminus of Y13 as the 14th amino acid residue (Y14). 【0030】Peptide B: In one embodiment, the peptide relating to the conjugate of the present invention includes the following amino acid sequence: dp4SNH2-3Py6Me-Gthp-Y3Me-HeG-4Py-N-mCPeG-Cba-P-D-YaeCopipzaa-C (SEQ ID NO: 215) or an amino acid sequence having substitutions, additions, deletions, or insertions in 1 to 9 amino acid residues arbitrarily selected from the group consisting of the 1st, 2nd, 3rd, 4th, 5th, 6th, 8th, 9th, and 12th amino acid residues of the above amino acid sequence. The amino acid sequence of SEQ ID NO: 215 may have substitutions, additions, deletions, or insertions in 1 to 9 amino acid residues arbitrarily selected from the group consisting of the 1st, 2nd, 3rd, 4th, 5th, 6th, 8th, 9th, and 12th amino acid residues. The number of substituted, deleted, added, and / or inserted amino acids may be between one and nine, with a lower limit of one. The upper limits are nine, eight, seven, six, five, four, three, and two, with a minimum of one. In one embodiment, the substitution, deletion, addition, and / or insertion of amino acids is preferably an amino acid "substitution." Non-limitingly, such amino acid substitutions are preferably conservative amino acid substitutions. A "conservative amino acid substitution" means a substitution with a functionally equivalent or similar amino acid. Conservative amino acid substitutions in a peptide result in a static change to the amino acid sequence of the peptide. For example, one or more amino acids with similar polarity act functionally equivalently and result in a static change to the amino acid sequence of such a peptide. In general, substitutions within a certain group can be considered structurally and functionally conservative. However, as is obvious to those skilled in the art, the role of a particular amino acid residue can be determined by its significance in the three-dimensional structure of the molecule containing that amino acid. For example, a cysteine ​​residue can take the less polar oxidized (disulfide) form compared to the reduced (thiol) form. The long aliphatic portion of the arginine side chain can constitute structurally and functionally important features.Furthermore, side chains containing aromatic rings (tryptophan, tyrosine, phenylalanine) can contribute to ion-aromatic interactions or cation-pi interactions. In such cases, substituting amino acids with these side chains with amino acids belonging to the acidic or nonpolar group may be structurally and functionally conserved. Residues such as proline, glycine, and cysteine ​​(disulfide form) can have a direct effect on the three-dimensional structure of the main chain and often cannot be substituted without structural distortion. 【0031】 Conservative amino acid substitutions include specific substitutions based on side chain similarity (e.g., substitutions described in L. Lehninger, Biochemistry, 2nd edition, pp. 73-75, Worth Publisher, New York (1975)) and typical substitutions, as shown below. Furthermore, for example, in groups of natural amino acids divided based on the properties of their common side chains, substitutions to amino acids belonging to the same group to which a given amino acid belongs are preferred. 【0032】Hydrophobic (also called nonpolar) amino acids: Amino acids that exhibit hydrophobicity (nonpolarity), including alanine ("Ala" or simply "A"), glycine ("Gly" or simply "G"), valine ("Val" or simply "V"), leucine ("Leu" or simply "L"), isoleucine ("Ile" or simply "I"), proline ("Pro" or simply "P"), phenylalanine ("Phe" or simply "F"), tryptophan ("Trp" or simply "W"), tyrosine ("Tyr" or simply "Y"), and methionine ("Met" or simply "M"). Hydrophobic amino acids can also be further divided into the following groups: Aliphatic amino acids: Amino acids that have fatty acids or hydrogen in their side chains, including Ala, Gly, Val, Ile, and Leu. Aliphatic branched-chain amino acids: Amino acids having branched fatty acids in their side chains, including Val, Ile, and Leu. Aromatic amino acids: Amino acids having aromatic rings in their side chains, including Trp, Tyr, and Phe. Hydrophilic (also called polar) amino acids: Amino acids that exhibit hydrophilicity (polarity), including serine ("Ser" or simply "S"), threonine ("Thr" or simply "T"), cysteine ​​("Cys" or simply "C"), asparagine ("Asn" or simply "N"), glutamine ("Gln" or simply "Q"), aspartic acid ("Asp" or simply "D"), glutamic acid ("Glu" or simply "E"), lysine (also written as lysine, "Lys" or simply "K"), arginine ("Arg" or simply "R"), and histidine ("His" or simply "H"). Hydrophilic amino acids can also be further divided into the following groups: Acidic amino acids: Amino acids whose side chains exhibit acidity, including Asp and Glu. Basic amino acids: Amino acids whose side chains are basic, including Lys, Arg, and His. 【0033】Neutral amino acids: Amino acids whose side chains are neutral, including Ser, Thr, Asn, Gln, and Cys. Gly and Pro can also be classified as "amino acids that affect the orientation of the main chain," and amino acids containing sulfur molecules in their side chains, Cys and Met, can also be classified as "sulfur-containing amino acids." In this specification, "amino acids" include not only natural amino acids but also unnatural amino acids. Unnatural amino acids include, for example, N-alkylated amino acids from the natural amino acids described above, and those modified with lower alkyl groups (e.g., C1-C5, preferably C1-C3, more preferably C1) whose nitrogen forming the peptide bond is branched or unbranched. N-alkyl amino acids are preferably N-ethyl amino acids, N-butyl amino acids, or N-methyl amino acids, and more preferably N-methyl amino acids. Furthermore, non-natural amino acids include D-type amino acids (also written as D-amino acids), β-amino acids, γ-amino acids, amino acid mutants, amino acid derivatives, and other chemically modified amino acids, as well as amino acids that do not become building blocks of proteins in the body, such as norleucine and ornithine. In addition, these include amino acids in which functional groups have been further added to the side chain of a natural amino acid or have been substituted with other functional groups (for example, amino acids with substitutions or additions to the arylene group, alkylene group, etc. of the side chain, amino acids with an increased number of carbon atoms in the arylene group, alkylene group, or alkyl group of the side chain, amino acids with substitutions in the aromatic ring of the side chain, and heterocyclic or fused amino acids). It should be noted that by adding or substituting functional groups or other structures to the side chain of a natural amino acid, properties different from those of the natural amino acid can be conferred. For example, Dap is an amino acid that has an amino group in the side chain of alanine, but due to the addition of this amino group, it exhibits the properties of a polar amino acid with basic properties, unlike alanine which belongs to the nonpolar amino acid group. In other words, the aforementioned groups, which classify natural amino acids based on the properties of their common side chains, can include non-natural amino acids that have similar side chain properties.For example, N-methylarginine (MeR), an amino acid in which the nitrogen atom of the main chain of arginine, a basic amino acid, is methylated, is a non-natural amino acid, but because it exhibits basicity, it can be classified as a basic amino acid. In this way, non-natural amino acids that exhibit the same side-chain properties as a certain amino acid can also be included as targets for conservative amino acid substitution. Furthermore, D-amino acids such as de (D-glutamic acid) can be classified as D-amino acids, but they can also be classified according to the properties of their side chains. Similarly, N-methyl amino acids can be classified as N-alkyl amino acids, or they can be classified according to the properties of the side chain of the original amino acid that has not been N-methylated. 【0034】 Non-specifically, non-natural amino acids include N-methyl amino acids, D-amino acids, and more specifically, 3FPeG, 3Py, 3Py5CON, 3Py6CON, 3Py6Et, 3Py6Me, 3Py6mor, 3Py6NH2, 3Py6NHaa, 3Py6O4pip1Ac, 3Py6O4thp, 3Py6OMe, 3Py6pipz4Ac, 4Py, 4Py3CON, 4Pyz, 4Pyz1Me, 5Pyrm, AcaeG, AcapG, aMeC, Atp, bA2SMe, PEG12c, Cba, Cbg, Cha, CmG, CmmG, CmpG, da, Dab, dd, This includes amino acids such as ddab, ddap, df4COO, dhgl, dk, dkAc, dkCopipzaa, dn, dorn, dp, dp4SNH2, ds, dyae, EtG, F3CON, F4aao, F4C, F4CON, F4F, F4Me, F4OMe, Gthp, HeG, Hpr, Hse, HseMe, IMe, mCPeG, Meda, Medn, Meds, MeG, MeopG, MeS, Ndm, Nmm, oCPeG, PeG, PEG10c, PEG4c, PEG8c, Tbg, W7N, Y3Me, Yae, YaeAc, and YaeCopipzaa. 【0035】"A pharmaceutically acceptable salt" refers to a salt of any of the peptides. Examples of pharmaceutically acceptable salts include salts with mineral acids such as sulfuric acid, hydrochloric acid, and phosphoric acid; salts with organic acids such as acetic acid, oxalic acid, lactic acid, tartaric acid, fumaric acid, maleic acid, methanesulfonic acid, and benzenesulfonic acid; salts with amines such as trimethylamine and methylamine; or salts with metal ions such as sodium ions, potassium ions, and calcium ions. For compounds that have acquired water over time, such water is also included in the pharmaceutically acceptable salts. 【0036】 Furthermore, the peptide may also be an isomer, such as a stereoisomer. A peptide may have one or more stereocenters, and these stereocenters may independently exist in either the (R) or (S) configuration. In this specification, the peptide may be an optically active compound or a racemate, and "may be an isomer" means including racemates, optically active compounds, positional isomers, and stereoisomers, or combinations thereof. In one embodiment, it may also be a mixture of one or more isomers. Note that "stereoisomer of a peptide" means a stereoisomer of the peptide. In this specification, when referring to a "peptide," its isomers are also included unless otherwise specified. 【0037】 Furthermore, the peptide may be a solvate. Solvation refers to the phenomenon in which a solute molecule (peptide or conjugate) diffuses into a solvent when ions produced by the ionization of the solute molecule and solvent molecules bind and surround each other by electrostatic force, hydrogen bonding, etc. The type of solvent is not particularly limited. When the solvent is water, it is specifically called a "hydrate". The following peptides are examples of peptide A and peptide B, respectively, which have been confirmed to have CLDN18.2 binding activity in the examples of this specification. 【0038】Peptide A: ddab-Tbg-F4CON-Gthp-Y3Me-HeG-4Py-N-mCPeG-Cba-P-D-C (SEQ ID NO: 136); a peptide in which the 13th amino acid residue of the amino acid sequence of SEQ ID NO: 136 is C or aMeC; and a peptide in which the 13th amino acid residue of the amino acid sequence of SEQ ID NO: 136 is A or G, and furthermore, G, MeG, Medn, Meda, dp, or Meds is added as the 14th amino acid residue to the C-terminus of the 13th amino acid residue. In one embodiment, peptide A of the present invention is: (1) the 13th amino acid residue of the amino acid sequence of SEQ ID NO: 136 is C or aMeC; or (2) the 13th amino acid residue of the amino acid sequence of SEQ ID NO: 136 is A or G, and furthermore, G, MeG, Medn, Meda, dp, or Meds is added as the 14th amino acid residue to the C-terminus of the 13th amino acid residue. The difference between (1) and (2) is the 13th amino acid residue. In one embodiment, if peptide A is a cyclic peptide, the number of amino acid residues included in the cyclic structure may be 13, 14, or more if there are further amino acids added to the terminal. 【0039】In one embodiment, peptide A is as follows: The first amino acid residue (of SEQ ID NO: 136) is da, dhgl, dp, ds, df4COO, dn, ddab, dk, dyae, dkCopipzaa, dd, dorn, or ddap; the second amino acid residue is S, 4Py, Cha, Tbg, W7N, F4aao, K, Yae, or IMe; the third amino acid residue is 3Py6NH2, F4CON, F4OMe, F4Me, or Y; the fourth amino acid residue is Y, F4C, F4F, 3Py6NHaa, Atp, V, Cha, 5Pyrm, F4aao, Tbg, Gthp, Cbg, YaeAc, Yae, or YaeCopipzaa; The fifth amino acid residue is 3Py6NH2, Y, or Y3Me; the sixth amino acid residue is MeG, HeG, CmG, PeG, AcaeG, CmpG, CmmG, MeopG, or AcapG; the seventh amino acid residue is S, 4Py, Nmm, Ndm, HseMe, Hse, 4Pyz1Me, 3Py5CON, 4Py3CON, 3Py6pipz4Ac, K, Yae, YaeCOPipzaa, 3Py6O4thp, F4CON, 3Py6O4pip1Ac, 3Py6CON, 3Py6mor, or 4Pyz; the eighth amino acid residue is N; the ninth amino acid residue is PeG, mCPeG, or oCPeG; The 10th amino acid residue is L or Cba; and the 11th amino acid residue is P or Hpr; and the 12th amino acid residue is D; one or more of these requirements are met. The above-mentioned options for the 1st to 12th amino acid residues can be selected in any combination. Not limited to, the above requirements are met in one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, and eleven or more requirements. Preferably, all of the above twelve requirements are met.Peptide A relating to the conjugate of the present invention is, in one embodiment, the following: The first amino acid residue of the amino acid sequence of SEQ ID NO: 136 is da, dhgl, dp, ds, df4COO, dn, ddab, dk, dyae, dkCopipzaa, dd, dorn, or ddap; the second amino acid residue is S, 4Py, Cha, Tbg, W7N, F4aao, K, Yae, or IMe; the third amino acid residue is 3Py6NH2, F4CON, F4OMe, F4Me, or Y; The fourth amino acid residue is Y, F4C, F4F, 3Py6NHaa, Atp, V, Cha, 5Pyrm, F4aao, Tbg, Gthp, Cbg, YaeAc, Yae, or YaeCopipzaa; the fifth amino acid residue is 3Py6NH2, Y, or Y3Me; the sixth amino acid residue is MeG, HeG, CmG, PeG, AcaeG, CmpG, CmmG, MeopG, or AcapG; The seventh amino acid residue is S, 4Py, Nmm, Ndm, HseMe, Hse, 4Pyz1Me, 3Py5CON, 4Py3CON, 3Py6pipz4Ac, K, Yae, YaeCOPipzaa, 3Py6O4thp, F4CON, 3Py6O4pip1Ac, 3Py6CON, 3Py6mor, or 4Pyz; the eighth amino acid residue is N; the ninth amino acid residue is PeG, mCPeG, or oCPeG; the tenth amino acid residue is L or Cba; and the eleventh amino acid residue is P or Hpr, and the twelfth amino acid residue is D, satisfying one or more of these requirements, and, (1) The 13th amino acid residue of the amino acid sequence of SEQ ID NO: 136 is C or aMeC; or (2) The 13th amino acid residue of the amino acid sequence of SEQ ID NO: 136 is A or G, and furthermore, G, MeG, Medn, Meda, dp, or Meds is added as the 14th amino acid residue to the C-terminus of the 13th amino acid residue. The above one embodiment of the options for the 1st to 12th amino acid residues can be selected in any combination. Non-limitingly, the above requirements are met by 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, or 11 or more.Preferably, all of the above 12 requirements are met. 【0040】 Peptide B; dp4SNH2-3Py6Me-Gthp-Y3Me-HeG-4Py-N-mCPeG-Cba-P-D-YaeCOPipzaa-C (SEQ ID NO: 215); a peptide in which the 13th amino acid residue of the amino acid sequence of SEQ ID NO: 215 is C or aMeC; and a peptide in which the 13th amino acid residue of the amino acid sequence of SEQ ID NO: 215 is N or bA2SMe, and furthermore, MeG or MeS is added as the 14th amino acid residue to the C-terminus of the 13th amino acid residue. 【0041】In one embodiment, peptide B according to the conjugate of the present invention is: (1) the 13th amino acid residue of the amino acid sequence of SEQ ID NO: 215 is C or aMeC; or (2) the 13th amino acid residue of the amino acid sequence of SEQ ID NO: 215 is N or bA2SMe, and furthermore, MeG or MeS is added as the 14th amino acid residue to the C-terminus of the 13th amino acid residue. The difference between (1) and (2) is the 13th amino acid residue. In one embodiment, if peptide B is a cyclic peptide, the number of amino acid residues included in the cyclic structure may be 13, 14, or more if there are further amino acids added to the terminal. Peptide B relating to the conjugate of the present invention is, in one embodiment, the following: The first amino acid residue of the amino acid sequence of Sequence ID No. 215 is da, dp, dk, dp4SNH2, dorn, or dkAc; the second amino acid residue is 3Py6NH2, F4OMe, 3Py6Me, 3Py6Et, or Y; the third amino acid residue is Y, N, Tbg, Yae, YaeAc, or Gthp; the fourth amino acid residue is Y or Y3Me; the fifth amino acid residue is MeG, EtG, HeG, or AcaeG; the sixth amino acid residue is 4Py, 3Py6OMe, 3Py, or 3Py6CON; the seventh amino acid residue is N; the eighth amino acid residue is PeG, mCPeG, or 3FPeG; The ninth amino acid residue is L or Cba; the tenth amino acid residue is P; and the eleventh amino acid residue is D; and the twelfth amino acid residue is 3Py6NH2, 4Py, Y3Me, YaeCOPipzaa, Yae, YaeAc, or F3CON; one or more of these requirements are met. The above one-instance selection of the first to twelfth amino acid residues can be chosen in any combination. Non-limitingly, the above requirements are met in one or more cases: two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, or eleven or more. Preferably, all of the above twelve requirements are met. 【0042】Peptide B relating to the conjugate of the present invention is, in one embodiment, the following: The first amino acid residue of the amino acid sequence of Sequence ID No. 215 is da, dp, dk, dp4SNH2, dorn, or dkAc; the second amino acid residue is 3Py6NH2, F4OMe, 3Py6Me, 3Py6Et, or Y; the third amino acid residue is Y, N, Tbg, Yae, YaeAc, or Gthp; the fourth amino acid residue is Y or Y3Me; the fifth amino acid residue is MeG, EtG, HeG, or AcaeG; the sixth amino acid residue is 4Py, 3Py6OMe, 3Py, or 3Py6CON; the seventh amino acid residue is N; the eighth amino acid residue is PeG, mCPeG, or 3FPeG; The ninth amino acid residue is L or Cba; the tenth amino acid residue is P; and the eleventh amino acid residue is D; the twelfth amino acid residue is 3Py6NH2, 4Py, Y3Me, YaeCOPipzaa, Yae, YaeAc, or F3CON, satisfying one or more of the requirements, and (1) the thirteenth amino acid residue of the amino acid sequence of SEQ ID NO: 215 is C or aMeC; or (2) the thirteenth amino acid residue of the amino acid sequence of SEQ ID NO: 215 is N or bA2SMe, and furthermore, MeG or MeS is added as the fourteenth amino acid residue to the C-terminus of the thirteenth amino acid residue. 【0043】 The options for the 1st to 12th amino acid residues in the above embodiment can be selected in any combination. Non-limitingly, the above requirements are met by 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, and 11 or more. Preferably, all of the above 12 requirements are met. 【0044】In one embodiment, the peptides related to the conjugate of the present invention may have further modifications to the amino acids they contain. Modification refers to, for example, the attachment of other compounds to the side chain ends of amino acids. For example, low- or medium-sized molecular weight compounds such as PEG or glycans may be attached to the side chain ends of lysine, aspartic acid, glutamic acid, arginine, glutamine, or tyrosine, or other amino acids may be attached. 【0045】 Furthermore, the peptide relating to the conjugate of the present invention is, in one embodiment, a cyclic peptide. A "cyclic peptide" refers to a peptide in which two amino acids are linked together, and all or part of it is cyclic. The peptide also includes those in which amino acids in the peptide form a cross-linking structure, those in which a cyclic structure is formed by lactam ring formation or macrocyclization reaction, and those having a lasso-peptide-like structure. In other words, the cyclic peptide only needs to have a part of it that forms a cyclic structure, and may also have a linear portion. 【0046】 Peptides generally have poor metabolic stability in vivo and their large size makes them difficult to permeate cell membranes. To address these challenges, methods such as cyclization of peptides have been employed. Cyclization of peptides has been shown to improve protease resistance and metabolic stability, and to restrict conformational changes, thereby increasing rigidity and improving membrane permeability and affinity to target proteins. 【0047】In one embodiment, the peptide has a cyclic structure in which a chloroacetylated amino acid, preferably an N-terminal amino acid (the first amino acid residue), is bonded to a cysteine ​​residue contained in the peptide. In one embodiment, the peptide has a cyclic structure in which an N-terminal amino acid (the first amino acid residue) is bonded to a cysteine ​​residue (or a substituted cysteine ​​residue, or a compound containing an -SH group internally) contained in the peptide. In one embodiment, the peptide has a cyclic structure in which an N-terminal amino acid (the first amino acid residue) is bonded to a 13th cysteine ​​residue contained in the peptide (including cysteine ​​substitutions such as N-methylcysteine). In one embodiment, the peptide has a cyclic structure in which a chloroacetylated N-terminal amino acid (the first amino acid residue) is bonded to a 13th cysteine ​​residue contained in the peptide or an -SH group contained in a compound (group) having an -SH group. Examples of compounds (groups) having an -SH group include MeCt. "Chloroacetylation" may also be "halogen acetylation" with other halogens. Furthermore, "acetylation" may also refer to "acylation" by an acyl group other than an acetyl group. In one embodiment, the peptide has a cyclic structure obtained by linking the first amino acid residue of the chloroacetylated amino acid sequence of SEQ ID NO: 136 or 215 with a cysteine ​​residue contained in the peptide. In one embodiment, the peptide may have a structure in which the amino acid sequence described in any of SEQ ID NOs: 1-223 and cysteine ​​or its substitutes contained in the peptide are linked via an acetyl group. That is, in this specification, for example, "cyclic peptide consisting of SEQ ID NO: XX" also includes a cyclic structure in which the amino acid sequence represented by SEQ ID NO: XX is linked with an acetyl group attached to the first amino acid contained in the amino acid sequence and a sulfur atom (S) contained in cysteine ​​or its substitutes and compounds having a -SH group. 【0048】In this specification, some amino acids may be modified for the purpose of cyclizing peptides. Such partially modified amino acids are also included. For example, as described above, a chloroacetyl group (ClAc group) may be added to the N-terminal amino acid and then bound to a cysteine ​​residue or an amino acid residue having an -SH group in the peptide to form a cyclamen. Various (natural / unnatural) amino acids to which such chloroacetyl groups have been added are also included in the amino acids of this application. 【0049】 In one embodiment, the peptide has a cyclic structure in which the N-terminal amino acid (the first amino acid residue) is bonded to the C-terminal amino acid (the amino acid at the very C-terminus if the 13th or 14th amino acid residue, etc., is added to the C-terminal side of the amino acid sequence of SEQ ID NO: 136 and / or 215). In one embodiment, the peptide has a cyclic structure in which the amino group of the N-terminal amino acid (the first amino acid residue) is bonded to the carboxyl group of the 13th amino acid contained in the peptide. In another embodiment, an additional amino acid may be added to the 13th amino acid residue, and the peptide may have a cyclic structure in which the N-terminal amino acid (the first amino acid residue) is bonded to the 13th amino acid residue, for example, the 14th and 15th amino acid residues. In one embodiment, the peptide has a cyclic structure in which the amino group of the first amino acid residue of the amino acid sequence of SEQ ID NO: 136 and / or 215 contained in the peptide is bonded to the carboxyl group of the 14th amino acid residue. In one embodiment, the peptide has a cyclic structure in which the amino group of the N-terminal amino acid (the first amino acid residue) is bonded to a functional group located at the end of the side chain of the C-terminal amino acid contained in the peptide. 【0050】In one embodiment, the peptide comprises or consists of the amino acid sequence described in any one of SEQ ID NOs: 1-223. In one embodiment, the peptide is a cyclic peptide comprising or consisting of the amino acid sequence described in any one of SEQ ID NOs: 1-223. The peptide is a peptide comprising the amino acid sequence described in any one of SEQ ID NOs: 1-223, or a peptide comprising an amino acid sequence in which 1-13 or 14 (preferably 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 2, or 1) amino acid residues are substituted, deleted, inserted, or added. In the case of sequences to which amino acid residues are added, if the added portion is a linker, many more amino acid residues (e.g., 1-14 residues) may be added. Furthermore, peptides comprising these amino acid sequences to which amino acid residues are substituted, deleted, inserted, or added are preferably, for example, those having CLDN18.2 binding activity. 【0051】 The peptide may contain additional amino acid residues in addition to the amino acid sequence of SEQ ID NO: 136 and / or 215. Non-limitingly, the peptide may contain additional amino acid residues in addition to the amino acid sequence of SEQ ID NO: 1-223. 【0052】 The "additional amino acid residues" may be contained within a cyclic peptide, or further amino acid residues may be added to the cyclic peptide in a linker-like manner. In one embodiment, they may be attached to the side chains of amino acid residues contained in the cyclic peptide. The number of amide bonds (number and length of amino acids) in the peptide and peptide moiety are not particularly limited. 【0053】Furthermore, a linker may be added to the cyclic peptide. Examples of linkers include the aforementioned amino acid linkers (peptide linkers), chemical linkers, fatty acid linkers, nucleic acid linkers, and glycan linkers, and may also be a complex of, for example, a chemical linker and a peptide linker. A chemical linker may be, for example, a PEG linker consisting of 1 to 24 ethylene glycol units. Alternatively, the linker may be a fatty acid linker containing a divalent chemical moiety derived from a fatty acid. The amino acid (peptide) linker is a linker containing at least one amino acid, and for example, a glycine-rich peptide such as a peptide having the sequence [Gly-Gly-Gly-Gly-Ser]n (wherein n is 1, 2, 3, 4, 5, or 6) as described in U.S. Patent No. 7,271,149, or a serine-rich peptide linker as described in U.S. Patent No. 5,525,491 can be used. Furthermore, non-limitingly, amino acids such as F, G, df, dnle, and t4amCh, or peptide linkers consisting of two or more linked amino acids, can be used. Note that in peptide linkers, the bond between amino acids or between amino acids and the chemical linker may be mediated via the side chains of the amino acids. Non-limitingly, the addition of a linker may change the physical properties of the peptide (e.g., solubility). 【0054】 The linker may be attached anywhere. For example, it may be attached to an amino acid residue located at the C-terminus, or to an amino acid residue included in the cyclic peptide. In one embodiment, the peptide contains a linker at its C-terminus. Preferably, the linker is attached to the side chain of an amino acid residue included in the cyclic peptide, or to a compound having a Cys,-SH group located at the C-terminus, or to any amino acid residue. More preferably, for peptide A, the linker is attached to the side chain of the 1st, 2nd, 4th, or 7th amino acid residue, and for peptide B, the linker is attached to the side chain of the 1st, 3rd, or 12th amino acid residue. 【0055】In one embodiment, the peptide is a peptide to which a linker and / or payload can be bound at the C-terminus. In one embodiment, peptide A is a peptide to which the 1st, 2nd, 4th, and 7th amino acid residues, or amino acid residues located towards the C-terminus or additional amino acid residues, are amino acid residues to which a linker and / or payload can be bound. 【0056】 In one embodiment, peptide B is a peptide in which the 1st, 3rd, 12th amino acid residues, or the C-terminal amino acid residues or additional amino acid residues are amino acid residues to which a linker and / or payload can be bound. 【0057】 An amino acid residue to which a linker and / or payload can be bound is an amino acid residue having a functional group to which a linker and / or payload can be bound at the side chain terminus of that amino acid residue, or, in the case of an amino acid residue located at the C-terminus or an additional amino acid residue, an amino acid residue having a functional group to which a linker and / or payload can be bound at its side chain terminus or C-terminus. The payload will be described later. Furthermore, the peptide may form a polymer via a linker or the like. The number of peptides contained in the polymer is not limited. In one embodiment, the polymer is a dimer, trimer, tetramer, pentamer, hexamer, octamer, or more. The polymer may contain multiple identical peptides or multiple different peptides. 【0058】CLDN18.2 Binding Activity In one embodiment, preferably, the peptide has CLDN18.2 binding activity. CLDN18.2 (Claudin18.2) is a 27.8 kDa four-transmembrane protein that constitutes tight junctions (TJs) between gastric mucosal epithelial cells (Genbank accession numbers NM_001002026, NP_001002026). The term "CLDN18.2" preferably refers to human CLDN18.2. In normal tissue, CLDN18.2 is expressed only in transiently differentiated gastric epithelial cells of the gastric mucosa. In contrast, CLDN18.2 expression in gastric cancer cells changes from TJs to the cell surface, and is therefore often presented on the surface of human gastric cancer cells. CLDN18.2 expression has been confirmed in various tumor tissues. For example, CLDN18.2 expression has been found in gastric cancer, esophageal cancer, pancreatic cancer, bronchial cancer, breast cancer, and ENT tumors. CLDN18.2 is an important target for the prevention and / or treatment of primary tumors such as gastric cancer, esophageal cancer, pancreatic cancer, lung cancers including non-small cell lung cancer (NSCLC), ovarian cancer, colon cancer, liver cancer, head and neck cancer, and gallbladder cancer, as well as their metastases, particularly gastric cancer metastases such as Krukenberg tumor, peritoneal metastasis, and lymph node metastasis. 【0059】 In this specification, CLDN18.2 binding activity means specific binding to CLDN18.2, particularly human CLDN18.2. Unless otherwise specified in this specification, CLDN18.2 binding activity means binding activity to CLDN18.2. 【0060】Non-limitingly, the binding state of the peptide conjugate of the present invention to CLDN18.2 can be expressed using indicators such as the affinity constant Ka, the dissociation constant Kd (also written as KD), the binding rate constant kon, and the dissociation rate constant koff. The affinity constant Ka and the dissociation constant Kd are indicators of the binding affinity, i.e., the strength of the bond, between two molecules in equilibrium, and the dissociation constant Kd is the reciprocal of the affinity constant Ka. The smaller the value of the dissociation constant Kd, the stronger the bond. On the other hand, the rate of the binding and dissociation reaction between two molecules in equilibrium is indicated by the binding rate constant kon and the dissociation rate constant koff, which are determined by reaction kinetic analysis, and Kd = koff / kon. Therefore, even when the dissociation constant Kd is the same, there are cases where the molecules associate slowly but dissociate slowly (both kon and koff values ​​are small) and cases where they associate quickly and dissociate quickly (both kon and koff values ​​are large), and the binding retention states in each case are completely different. 【0061】 The affinity constant Ka, dissociation constant Kd (also written as KD), binding rate constant kon, and dissociation rate constant koff, which indicate the binding state of the peptide to CLDN18.2, can be determined using any intermolecular interaction measurement method well known to those skilled in the art. 【0062】 The binding state of the peptide to CLDN18.2 can be measured by known methods. Examples of such measurement methods include, but are not limited to, surface plasmon resonance spectroscopy (SPR), scatchard analysis and / or radioimmunoassay (RIA), enzyme immunoassay, and competitive binding assays such as sandwich competition assays. For example, surface plasmon resonance spectroscopy can be performed using a biosensor (biomolecular interaction analyzer) such as the BIACORE system (Cytiva). 【0063】The Kd dissociation constant is one indicator of the CLDN18.2 binding activity of the peptide. A lower dissociation constant Kd indicates higher binding activity (affinity). According to surface plasmon resonance spectroscopy, the dissociation constant Kd for binding between the peptide and, for example, human CLDN18.2 is non-limitingly 50 nM or less, 30 nM or less, 20 nM or less, 15 nM or less, 10 nM or less, 8 nM or less, 6 nM or less, 5 nM or less, 4 nM or less, 3 nM or less, 2 nM or less, and 1 nM or less. The lower limit of the dissociation constant Kd for binding between the peptide and CLDN18.2 is not particularly limited. Non-limitingly, the peptide dissociation constant Kd is 0.0001 nM or greater, 0.001 nM or greater, 0.01 nM or greater, 0.05 nM or greater, 0.1 nM or greater, 0.2 nM or greater, 0.3 nM or greater, 0.4 nM or greater, or 0.5 nM or greater. Non-limitingly, the peptide dissociation constant Kd is 0.0001-500 nM, 0.001-100 nM, 0.01-50 nM, preferably 0.05-30 nM, more preferably 0.2-15 nM, particularly preferably 0.3-10 nM, and most preferably 0.4-5 nM. The binding of the peptide to CLDN18.2 can also be examined, for example, by ELISA (enzyme-linked immunosorbent assay). ELISA may also be performed, for example, by examining the binding activity using CLDN18.2 beads and a peptide with an HA tag sequence added to its C-terminus. 【0064】Non-limitingly, the binding of the peptide to CLDN18.2 is preferably a non-covalent bond. In one embodiment, the peptide has a cyclic structure as shown in the peptide portion of the chemical formulas of Examples 1-1 to 1-19. Peptides having CLDN18.2 binding activity are effective for the evaluation, diagnosis, and treatment of various diseases involving CLDN18.2. In one embodiment, the present invention relates to the peptide having CLDN18.2 binding activity. In one embodiment, the present invention relates to the use of the peptide for binding to CLDN18.2. In one embodiment, the present invention relates to the peptide used for binding to CLDN18.2. In the present invention, the binding of the peptide of the present invention to CLDN18.2 is in vitro or in vivo. Matters described in other sections also apply to this section unless otherwise specified. 【0065】4. Peptide Production The peptides relating to the conjugate of the present invention can be produced by any known method for peptide production, such as the following: Matters described in other sections also apply to this section unless otherwise specified. Chemical synthesis methods such as liquid-phase methods, solid-phase methods, and hybrid methods combining liquid-phase and solid-phase methods; genetic engineering methods, etc. The solid-phase method involves, for example, esterifying the hydroxyl group of a resin having a hydroxyl group with the carboxyl group of a first amino acid (usually the C-terminal amino acid of the target peptide) whose α-amino group is protected by a protecting group. Known dehydration condensation agents such as 1-mesitylenesulfonyl-3-nitro-1,2,4-triazole (MSNT), dicyclohexylcarbodiimide (DCC), and diisopropylcarbodiimide (DIC) can be used as esterification catalysts. Next, the protecting group of the α-amino group of the first amino acid is removed, and a second amino acid, in which all functional groups except the carboxyl group of the main chain are protected, is added. The carboxyl group is then activated to bond the first and second amino acids. Furthermore, the α-amino group of the second amino acid is deprotected, and a third amino acid, in which all functional groups except the carboxyl group of the main chain are protected, is added. The carboxyl group is then activated to bond the second and third amino acids. This process is repeated until a peptide of the desired length is synthesized, at which point all functional groups are deprotected. 【0066】 Examples of solid-phase synthesized resins include Merrifield resin, MBHA resin, Cl-Trt resin, SASRIN resin, Wang resin, Rink amide resin, HMFS resin, Amino-PEGA resin (Merck), and HMPA-PEGA resin (Merck). These resins can be used after washing with a solvent (dimethylformamide (DMF), 2-propanol, methylene chloride, etc.). 【0067】Examples of protecting groups for the α-amino group include benzyloxycarbonyl (Cbz or Z) group, tert-butoxycarbonyl (Boc) group, 9-fluorenylmethyloxycarbonyl (Fmoc) group, benzyl group, allyl group, and allyloxycarbonyl (Alloc) group. The Cbz group can be deprotected by hydrofluoric acid, hydrogenation, etc., the Boc group can be deprotected by trifluoroacetic acid (TFA), and the Fmoc group can be deprotected by treatment with piperidine or pyrrolidine. For protecting the α-carboxyl group, for example, methyl esters, ethyl esters, allyl esters, benzyl esters, tert-butyl esters, cyclohexyl esters, etc. can be used. 【0068】 Carboxylate activation can be performed using a condensing agent. Examples of condensing agents include dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC or WSC), (1H-benzotriazole-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), and 1-[bis(dimethylamino)methyl]-1H-benzotriazolium-3-oxidehexafluorophosphate (HBTU). Cleavage of peptide chains from the resin can be performed by treatment with an acid such as TFA or hydrogen fluoride (HF). 【0069】 The production of peptides by genetic engineering (translation synthesis system) can be carried out using nucleic acids encoding the peptide. The nucleic acids encoding the peptide may be DNA or RNA. The nucleic acids encoding the peptide can be prepared by known methods or similar methods. For example, they can be synthesized by an automated synthesis apparatus. Restriction enzyme recognition sites may be added to insert the obtained DNA into a vector. Alternatively, a base sequence encoding an amino acid sequence for cleaving the resulting peptide chain with an enzyme may be incorporated. 【0070】To suppress degradation by host-derived proteases, a chimeric protein expression method can be used, in which the target peptide is expressed as a chimeric peptide with another peptide. In this case, the nucleic acid used is one which encodes the target peptide and the peptide that binds to it. Subsequently, an expression vector is prepared using the nucleic acid encoding the peptide. The nucleic acid can be inserted downstream of the promoter of the expression vector, either as is, digested with restriction enzymes, or with the addition of a linker. Examples of vectors include E. coli plasmids (pBR322, pBR325, pUC12, pUC13, pUC18, pUC19, pUC118, pBluescript II, etc.), Bacillus subtilis plasmids (pUB110, pTP5, pC1912, pTP4, pE194, pC194, etc.), yeast plasmids (pSH19, pSH15, YEp, YRp, YIp, YAC, etc.), bacteriophages (e-phage, M13 phage, etc.), viruses (retroviruses, vaccinia virus, adenovirus, adeno-associated virus (AAV), cauliflower mosaic virus, tobacco mosaic virus, baculovirus, etc.), and cosmids. Promoters can be appropriately selected depending on the host type. When the host is an animal cell, for example, promoters derived from SV40 (Simian virus 40) or CMV (Cytomegalovarum) can be used. When the host is Escherichia coli, promoters such as trp promoter, T7 promoter, and lac promoter can be used. 【0071】 Expression vectors can also incorporate nucleic acids that encode, for example, DNA replication start sites (ORI), selection markers (antibiotic resistance, nutritional requirements, etc.), enhancers, splicing signals, poly-A addition signals, and tags (FLAG, HA, GST, GFP, etc.). 【0072】Next, a suitable host cell is transformed with the expression vector. The host can be appropriately selected in relation to the vector. Examples of hosts include Escherichia coli, Bacillus subtilis, Bacillus species, yeast, insects or insect cells, and animal cells. Examples of animal cells include HEK293T cells, CHO cells, COS cells, myeloma cells, HeLa cells, and Vero cells. Transformation can be carried out according to known methods such as lipofection, calcium phosphate, electroporation, microinjection, and particle gun, depending on the type of host. By culturing the transformed cells according to conventional methods, the target peptide is expressed. 【0073】 Peptide purification from transformant cultures involves harvesting the cultured cells, suspending them in a suitable buffer, disrupting the cells by methods such as sonication or freeze-thaw cycles, and obtaining a crude extract by centrifugation or filtration. If peptides are secreted into the culture medium, the supernatant is collected. 【0074】 Purification from the crude extract or culture supernatant can also be carried out by known methods or equivalent methods (e.g., salting out, dialysis, ultrafiltration, gel filtration, SDS-PAGE, ion exchange chromatography, affinity chromatography, reverse-phase high-performance liquid chromatography, etc.). The obtained peptide may be converted from free form to salt, or from salt to free form, by known methods or equivalent methods. 【0075】 In one embodiment, the translation synthesis system may be a cell-free translation system. Generally, with a cell-free translation system, the expression product can be obtained in a highly pure form without purification. The cell-free translation system includes, for example, ribosomal proteins, aminoacyl-tRNA synthetase (ARS), ribosomal RNA, amino acids, rRNA, GTP, ATP, translation initiation factor (IF), elongation factor (EF), termination factor (RF), and ribosomal regeneration factor (RRF), as well as other factors necessary for translation. E. coli extract or wheat germ extract may be added to increase expression efficiency. Alternatively, rabbit red blood cell extract or insect cell extract may be added. 【0076】By continuously supplying energy to a system containing these components using dialysis, proteins can be produced in amounts ranging from several hundred μg to several mg / mL without limitation. The system may also include RNA polymerase to facilitate transcription from gene DNA. Commercially available cell-free translation systems include Roche Diagnostics' RTS-100 (registered trademark), Gene Frontier's PURESYSTEM, and New England Biolabs' PUREexpress In Vitro Protein Synthesis Kit, which are derived from E. coli, and systems from Zoygene and Cellfree Sciences, which can be used. 【0077】 In cell translation systems, artificial aminoacyl-tRNA may be used instead of aminoacyl-tRNA synthesized by natural aminoacyl-tRNA synthetase, by cylating (acylating) a desired amino acid or hydroxy acid to the tRNA. Such aminoacyl-tRNA can be synthesized using artificial ribozymes. Examples of such ribozymes include flexizymes (H. Murakami, H. Saito, and H. Suga, (2003), Chemistry & Biology, Vol. 10, 655-662; and WO2007 / 066627, etc.). Flexizymes are also known by the names of the original flexizyme (Fx), and modified versions thereof such as dinitrobenzylflexizyme (dFx), enhanced flexizyme (eFx), and aminoflexizyme (aFx). 【0078】 By using tRNA linked to a desired amino acid or hydroxy acid, generated by Flexizyme, a desired codon can be translated in association with the desired amino acid or hydroxy acid. Special amino acids may be used as the desired amino acid. For example, unnatural amino acids necessary for the cyclization described above can also be introduced into the bound peptide by this method. 【0079】The chemical synthesis of the peptide can be carried out using various methods commonly used in the art, including, for example, stepwise solid-phase synthesis, semi-synthesis of peptide fragments via conformationally supported re-ligation, and chemical ligation. The synthesis of the peptide is a chemical synthesis using various solid-phase techniques, as described, for example, in K. J. Jensen, P. T. Shelton, S. L. Pedersen, Peptide Synthesis and Applications, 2nd Edition, Springer, 2013. A preferred strategy is based on a combination of an Fmoc group that temporarily protects the α-amino group and allows for selective removal by a base, and a protecting group that temporarily protects the side-chain functional group and is stable under de-Fmoc conditions. Such common peptide side chain selections are found in the aforementioned *Peptide Synthesis and Applications*, 2nd edition, and G. B. Fields, R. L. Noble, *Solid Phase Peptide Synthesis Utilizing 9-Fluorenylmethoxycarbonyl Amino Acids*, Int. J. Peptide Protein Res. As described in 35, 1990, 161-214, preferred peptide side chain protecting groups include, for example, benzyl, tert-butyl, and trityl (Trt) groups for the hydroxyl groups of serine and threonine; 2-bromobenzyloxycarbonyl and tert-butyl groups for the hydroxyl groups of tyrosine; Boc, methyltetrazolethiol (Mtt), Alloc, and ivDde groups for the amino groups of lysine side chains; and for the imidazole group of histidine. Examples include the Trt group and Boc group, the 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl (Pbf) group on the guanidyl group of arginine, the tert-butyl group, allyl group, and 3-methylpentane (Mpe) group on the carboxyl groups of glutamic acid and aspartic acid, the Trt group on the carboxamide group of glutamine and asparagine, and the Trt group and monomethoxytrityl (Mmt) group on the thiol group of cysteine. 【0080】The peptide can be synthesized stepwise on the solid-phase resin described above. The α-amino protecting group must be selectively removed from the C-terminal amino acid and all amino acids and peptides used in the synthesis process. Preferably, the solid-phase resin described above is used, and the synthesis is initiated by activating the C-terminal carboxyl group of a peptide whose N-terminus is appropriately protected with an Fmoc group, or the C-terminal carboxyl group of an amino acid protected with an Fmoc group, using an appropriate reagent, and then adding it to an amino group on the solid-phase resin. Subsequent peptide chain extension can be achieved by sequentially repeating the removal of the N-terminal protecting group (Fmoc group) and then the condensation of the protected amino acid derivative, according to the amino acid sequence of the target peptide. In addition, the target peptide can be released in the final stage. For example, as a condition for release, Teixeira, W. E. Benckhuijsen, P. E. de Koning, A. R. P. M. Valentijn, J. W. As cited in Drijfhout, Protein Pept. Lett., 2002, 9, 379-385, etc., TFA can be liberated in a TFA solution containing water / silyl hydride / thiol as a scavenger. A typical example is TFA / Water / TIS / DODT (volume ratio 92.5:2.5:2.5:2.5). 【0081】The peptides described herein can be synthesized using single or multi-channel peptide synthesizers, such as CEM's Liberty Blue synthesizer or Biotage's Syro I synthesizer or their successors. Carboxylate activation can be performed using a coupling agent. Examples of coupling agents include dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIPCDI), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC or WSC), (1H-benzotriazole-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), and 1-[bis(dimethylamino)methyl]-1H-benzotriazolium-3-oxidehexafluorophosphate (HBTU). Peptide cyclization can be performed according to known methods. Non-limitingly, for example, by designing a peptide to contain two or more cysteine ​​residues, a cyclic structure can be formed after translation via disulfide bonds. Alternatively, cyclization can be achieved by synthesizing a peptide with a chloroacetyl group at the N-terminus using genetic code reprogramming techniques, following the method of Goto et al. (Y. Goto, et al. ACS Chem. Biol. 3 120-129 (2008)), and then placing a cysteine ​​residue containing a sulfur molecule within the peptide. This allows the mercapto group to spontaneously nucleophilically attack the chloroacetyl group after translation, resulting in cyclization of the peptide via thioether bonds. Cyclization may also be achieved by placing other combinations of amino acids that bind to form a ring within the peptide using genetic code reprogramming techniques. Alternatively, cyclization may be achieved by placing an L-2-aminoadipic acid residue within the peptide and bonding it with the N-terminal main chain amino group. Alternatively, cyclization may be performed by linking the amino group of the N-terminal amino acid residue with the carboxyl group of the C-terminal amino acid residue via an amide bond. Furthermore, cyclization may be performed by linking the amino group of the N-terminal amino acid (the first amino acid residue) with a functional group present at the end of the side chain of the C-terminal amino acid contained in the peptide. Thus, any known cyclization method can be used without particular limitation.Unless otherwise specified, matters described in other sections also apply to this section. 【0082】 5. Payload In this specification, payload refers to a molecule and its precursor that exhibit a desired function by binding to or acting on a target. In one embodiment, the desired function may include pharmacological activity or labeling function. 【0083】 In this specification, the payload comprises a radioisotope and / or a chelating agent. By providing a payload containing a radioisotope in the conjugate of the present invention, the radioisotope can be specifically delivered to cancer cells expressing CLDN18.2. This enables the labeling of CLDN18.2-expressing cancer cells with the radioisotope and CLDN18.2-expressing cancer cells with specific radiation. Furthermore, in this specification, the payload also includes embodiments that contain a chelating agent but do not contain a radioisotope. By providing a payload containing a chelating agent but not a radioisotope in the conjugate of the present invention, it is possible to manufacture and store it without considering radiation attenuation, and by conjugating a radioisotope to it in a timely manner, a conjugate that can be used for cancer treatment and diagnosis can be quickly obtained. 【0084】 Radioisotopes In this specification, radioisotopes (which may also be referred to as radioactive materials) are known radioisotopes that are effective in the examination, diagnosis, prevention, and / or treatment of CLDN18.2-related diseases. Without limitation, radioisotopes in this specification may be radionuclides that have therapeutic effects, specifically, radioisotopes that emit alpha rays or radioisotopes that emit beta rays. Because such radioisotopes can destroy cancer cells, they are suitably used in cancer treatment. 【0085】Furthermore, although not limited thereto, in this specification, radioactive isotopes may be those used for the diagnosis of cancer or the detection of lesions, specifically, radioactive isotopes that emit positrons or radioactive isotopes that emit gamma rays. The former can be suitably used in PET (Positron Emission Tomography) examinations, and the latter in SPECT (Single Emission Computed Tomography) examinations. 【0086】In one embodiment, the radioactive isotopes are actinium-225, actinium-227 (225Ac, 227Ac), astatine-211 (211At), bismuth-212 and bismuth-213 (212Bi, 213Bi), copper-61, copper-62, copper-64 and copper-67 (61Cu, 62Cu, 64Cu, 67Cu), gallium-64, gallium-67 and gallium-68 (64Ga, 67Ga, and 68Ga), indium-111 (111In), iodine-123, iodine-124, iodine-125, or iodine-131 (123I, 124I, 125I) , 131I), lead-203, lead-212 (203Pb, 212Pb), ruthenium-97 (97Ru), lutetium-177 (177Lu), radium-223 (223Ra), samarium-153 (153Sm), scandium-44 and scandium-47 (44Sc, 47Sc), iron-52 (52Fe), arsenic-72, arsenic-76 (72As, 76As), erbium-169 (169Er), strontium-89, strontium-90 (89Sr, 90Sr), technetium-99 (99mTc), technetium-94 (94mTc), it Thorium-86 and Yttrium-90 (86Y, 90Y), Chromium-51 (51Cr), Rhenium-186, Rhenium-188 (186Re, 188Re), Zirconium-89 (89Zr), Manganese-52, Manganese-51 (52Mn, 51Mn), Terbium-149, Terbium-152, Terbium-155, Terbium-161 (149Tb, 152Tb, 155Tb, 161Tb), Ytterbium-169, Ytterbium-175 (169Yb, 175Yb), Rhodium-105 (105Rh), Dysprosium-166 (166D y), holminium-166 (166Ho), samarium-153 (153Sm), bromotium-149, bromotium-151 (149Pm, 151Pm), thulium-172 (172Tm), tin-121 (121Sn), praseodymium-142, praseodymium-143 (142Pr, 143Pr), gold-198, gold-199 (198Au, 199Au), bromine-75, bromine-76, bromine-77, bromine-80, bromine-82 (75Br, 76Br, 77Br, 80Br, 82Br), fluorine-18 (18F), scandium-43, scandium-44,It contains elements such as scandium-47 (43Sc, 44Sc, 47Sc), astatine-211 (211At), thorium-227, thorium-226 (227Th, 226Th), lanthanum-140 (140La), rubidium-82 (82Rb), phosphorus-32 (32P), silver-111 (111Ag), erbium-165 (165Er), hydrogen-3 (3H), carbon-11 (11C), carbon-14 (14C), nitrogen-13 (13N), oxygen-15 (15O), krypton-81 (81mKr), xenon-133 (133Xe), and thallium-201 (201TI). 【0087】Based on common technical knowledge, radioactive isotopes can be directly bound to the peptide relating to the conjugate of the present invention, or via a linker or the like. Furthermore, the radioactive isotopes may or may not be bound to the chelating agent described below. Those skilled in the art can, based on common technical knowledge, select an appropriate embodiment considering the properties of each radioactive isotope. In one non-limiting embodiment, the payload may contain radioactive isotopes not bound to the chelating agent. In one embodiment, the payload may be a compound used in evaluation methods or imaging using radioactive isotopes, and for example, non-limitingly, it may be a known compound containing radioactive isotopes used as a radioligand imaging agent in positron emission tomography (PET) and SPECT. For example, non-limitingly, 18F-fluorodeoxyglucose (18F-FDG), 15O-H2O, 11C-methionine, 11C-acetic acid, 11C-choline, 11C-lacropride, 11C-flumazenyl, 13N-ammonia, 18F-sodium fluoride, 82Rn+(82RbCl), 18F-flurpyridaz, 123I-IMP, 99mTc-ECD, 99Tc-HMPAO, 123I-I These may be offlupan, 99mTcO4-(Na99mTcO4), 99mTcMIBI, 201TI+(201TICI), 99mcTc-tetrophosmin, 99mcTc-human serum albumin, 131O-adosterol, 99mTc-phytic acid, 90Y-zevalin, 67Ga+(67GaC6H5O7), 111In-ibritumomabutiuxetane, 111In-pentetreotide, etc. In one embodiment, the payload may also contain a radioisotope bound to a chelating agent, preferably a metallic radioisotope. In another embodiment, the payload may also contain a chelating agent for binding the radioisotope. 【0088】In this specification, a chelating agent refers to an organic compound that forms a cyclic complex by bonding with a metal ion in order to stably bond radioactive isotopes, particularly metallic radioactive isotopes.In one embodiment, the chelating agent is EDTA (ethylenediaminetetraacetic acid), DPTA (diethylenetriaminepentaacetic acid), 1,4,8,11-tetraazatetradecane, 1,4,8,11-tetraazatetradecane-1,4,8,11-tetraacetic acid, 1-oxa-4,7,12,15-tetraazaheptadecane-4,7,12,15-tetraacetic acid, DOTAGA (α-(2-carboxyethyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) (also called rDOTAGA), TMT ( 6,6''-bis[N,N'',N'''-tetra(carboxymethyl)aminomethyl)-4'-(3-amino-4-methoxyphenyl)-2,2':6',2''-terpyridine), DOTA(1,4,7,10-tetraazacyclododecane-NN',N''(N'''-tetraacetic acid), TCMC(tetra-primary amide of DOTA), DO3A(1,4,7,10-tetraazacyclododecane-1,4,7-tris(acetic acid)-10-(2-thioethyl)acetamide), CB-DO2A(4,10-bis(carboxymethyl) Methyl)-1,4,7,10-tetraazabicyclo[5.5.2]tetradecane), NOTA(1,4,7-triazabicyclononane-triacetic acid), Diamsar(3,6,10,13,16,19-hexazabicyclo[6.6.6]eicosane-1,8-diamine), DTPA(pentetic acid or diethylenetriaminepentaacetic acid), CHX-A''-DTPA([(R)-2-amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-pentaacetic acid), T This includes ETA (1,4,8,11-tetraazacyclotetradecane-1,4,8), 11-tetraacetic acid, Te2A (4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane), HBED, DFO (deferoxamine), DFOsq (DFO-squalamide), HOPO (3,4,3-(LI-1,2-HOPO), NODAGA (1,4,7-triazacyclononane-1-1-glutamic acid-4,7-acetic acid) (also known as rNODAGA), and modified versions thereof.In the present invention, the chelating agent only needs to be able to stably bind to the radioactive isotope, and can be appropriately selected based on common technical knowledge, taking into account the properties of the radioactive isotope used. Non-limited preferred examples of such chelating agents are DOTA, DOTAGA, or NODAGA. 【0089】 While not limited, in the present invention, the chelating agent may be in a form in which a radioactive isotope is not bound, or it may be in a form in which a radioactive isotope is bound. Examples of the latter include, but are not limited to, a structure in which a radioactive isotope of lutetium is bound to DOTA, a structure in which a radioactive isotope of zirconium is bound to DOTA, a structure in which a radioactive isotope of copper is bound to DOTA, and a structure in which a radioactive isotope of gallium is bound to DOTA. While not limited, when using the conjugate of the present invention for diagnosis or treatment, it is preferable to manufacture and store a conjugate in which a radioactive isotope is not bound in advance, taking into consideration that the radioactive isotope decays over time, and then bind the radioactive isotope at the appropriate time and administer it to the target recipient, such as a patient. That is, the conjugate of the present invention in which a radioactive isotope is not bound can be used as a semi-finished product for the timely and rapid production of a conjugate with a desired radioactive isotope bound as a pharmaceutical product. In other words, a conjugate of the present invention in which the payload contains a chelating agent but does not contain radioisotopes is also one aspect of the present invention. Another aspect of the present invention relates to the use of a radioisotope-free conjugate of the present invention for the production of a radioisotope-containing conjugate of the present invention. 【0090】 6. Compositions, etc. The present invention also relates to compositions comprising the conjugate of the present invention or a pharmaceutically acceptable salt thereof. The compositions are, not limited to, pharmaceutical compositions (medical compositions), diagnostic compositions, and research compositions. In one embodiment, the pharmaceutical composition is a composition used in radiotherapy (a form of a therapeutic composition). 【0091】The present invention also relates to an imaging agent comprising the conjugate of the present invention. The imaging agent may also be used as a diagnostic composition. In one embodiment, the diagnostic composition is an imaging agent. Matters described in other sections also apply to this section unless otherwise specified. 【0092】 Pharmaceutical Composition In one embodiment, the present invention relates to a pharmaceutical composition comprising the conjugate or a pharmaceutically acceptable salt thereof. In one embodiment, the pharmaceutical composition has CLDN18.2 binding activity. In one embodiment, the pharmaceutical composition is a pharmaceutical composition for preventing or treating CLDN18.2-related diseases. "CLDN18.2-related diseases" includes known CLDN18.2-related diseases and means diseases in which CLDN18.2 is expressed in cells of affected tissue or organs. In one embodiment, the expression of CLDN18.2 in cells of affected tissue or organs is increased compared to the state of healthy tissue or organs. The increase refers to an increase of at least 10%, particularly at least 20%, at least 50%, at least 100%, at least 200%, at least 500%, at least 1000%, at least 10000%, or more. In one embodiment, the expression is found only in affected tissue, while the expression is suppressed in healthy tissue. According to the present invention, diseases associated with cells expressing CLDN18.2 include cancerous diseases, such as tumors, particularly malignant tumors and solid tumors. Furthermore, according to the present invention, cancerous diseases are preferably cancerous diseases in which cancer cells express CLDN18.2. 【0093】In one embodiment, examples of CLDN18.2-related diseases include primary tumors such as gastric cancer, esophageal cancer, pancreatic cancer, lung cancer such as non-small cell lung cancer (NSCLC), breast cancer, ovarian cancer, colon cancer, liver cancer, head and neck cancer, and gallbladder cancer, as well as their metastases, particularly Krukenberg tumor, peritoneal metastasis, and lymph node metastasis of gastric cancer. CLDN18.2 is known to be expressed in these tumor tissues. In one embodiment, the pharmaceutical composition is a composition used in radiotherapy (one aspect of a therapeutic composition). Radiotherapy is a treatment method that involves irradiating the affected area with radiation or administering a radioactive substance to damage the DNA and other components within cells in tumors, particularly cancers, thereby killing the cells. Since the conjugate of the present invention contains a CLDN18.2-binding peptide, by using a payload containing a radioactive substance, the radioactive substance can be delivered to tumor tissue expressing CLDN18.2, and it can be destroyed specifically in the tumor tissue. 【0094】 The pharmaceutical composition may contain the conjugate itself, or it may contain a pharmaceutically acceptable salt, isomer, or solvate thereof of the conjugate. In this specification, "conjugate" may include a pharmaceutically acceptable salt, isomer, or solvate thereof unless otherwise specified. The pharmaceutical composition preferably contains an effective amount of the conjugate as an active ingredient. 【0095】 In this specification, the form of administration of the pharmaceutical composition is not particularly limited and may be administered orally or parenterally. Examples of parenteral administration include injection (such as intramuscular injection, intravenous injection, or subcutaneous injection), transdermal administration, and transmucosal administration (through the nose, mouth, eye, lung, vagina, or rectum). 【0096】The aforementioned pharmaceutical composition can be modified in various ways, taking into account the easily metabolized and excreted nature of polypeptides. For example, polyethylene glycol (PEG) or sugar chains can be added to the polypeptide to increase its blood retention time and reduce its antigenicity. Alternatively, biodegradable polymer compounds such as polylactic acid glycol (PLGA), porous hydroxyapatite, liposomes, surface-modified liposomes, emulsions prepared with unsaturated fatty acids, nanoparticles, nanospheres, etc., may be used as sustained-release bases, and polypeptides may be encapsulated within them. When administered transdermally, a weak electric current can be applied to the skin surface to allow penetration through the stratum corneum (iontophoresis). 【0097】 The aforementioned pharmaceutical composition may use the active ingredient as is, or it may be formulated by adding pharmaceutically acceptable carriers, excipients, additives, etc. Examples of dosage forms include liquids (e.g., injections), dispersants, suspensions, tablets, pills, powders, suppositories, powders, granules, capsules, syrups, lozenges, inhalants, ointments, eye drops, nasal drops, ear drops, poultices, etc. Formulation can be carried out by conventional methods, for example, by appropriately using excipients, binders, disintegrants, lubricants, solvents, solubilizers, colorants, flavoring and odor-correcting agents, stabilizers, emulsifiers, absorption enhancers, surfactants, pH adjusters, preservatives, antioxidants, etc. 【0098】Examples of ingredients used in formulation include, but are not limited to, purified water, saline solution, phosphate buffer, dextrose, glycerol, pharmaceutically acceptable organic solvents such as ethanol, animal and vegetable oils, lactose, mannitol, glucose, sorbitol, crystalline cellulose, hydroxypropylcellulose, starch, corn starch, anhydrous silicic acid, aluminum magnesium silicate, collagen, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, sodium carboxymethylcellulose, sodium polyacrylate, sodium alginate, water-soluble dextran, sodium carboxymethyl starch, pectin, methylcellulose, ethylcellulose, xanthan gum, acacia gum, tragacanth, casein, agar, polyethylene glycol, diglycerin, glycerin, propylene glycol, petrolatum, paraffin, octyldodecyl myristate, isopropyl myristate, higher alcohols, stearyl alcohol, stearic acid, human serum albumin, etc. 【0099】 In view of the fact that peptides are generally poorly absorbed through mucosal channels, the aforementioned pharmaceutical composition may contain an absorption enhancer to improve the absorption of poorly absorbed drugs. Examples of such absorption enhancers include surfactants such as polyoxyethylene lauryl ethers, sodium lauryl sulfate, and saponins; bile salts such as glycocholic acid, deoxycholic acid, and taurocholic acid; chelating agents such as EDTA and salicylic acids; fatty acids such as caproic acid, capric acid, lauric acid, oleic acid, linoleic acid, and mixed micelles; enamine derivatives, N-acyl collagen peptides, N-acyl amino acids, cyclodextrins, chitosans, and nitric oxide donors. 【0100】If the pharmaceutical composition is in the form of a pill or tablet, it may be coated with a sugar coating, gastric-soluble or enteric-soluble substance. If the pharmaceutical composition is an injectable preparation, it may contain distilled water for injection, physiological saline, propylene glycol, polyethylene glycol, vegetable oil, alcohols, etc. Furthermore, humectants, emulsifiers, dispersants, stabilizers, solvents, solubilizers, preservatives, etc. may be added. In addition, the pharmaceutical composition may be intended not only for humans but also for non-human mammals or birds. Examples of non-human mammals include primates other than humans (monkeys, chimpanzees, gorillas, etc.), domestic animals (pigs, cattle, horses, sheep, etc.), or dogs, cats, rats, mice, guinea pigs, rabbits, etc. 【0101】 In particular, the dosage when administered to humans varies depending on the symptoms, the patient's age, sex, weight, sensitivity differences, method of administration, administration interval, type of active ingredient, and type of formulation. Non-limitedly, for example, 30 μg-100 g, 100 μg-500 mg, or 100 μg-100 mg can be administered in one or several divided doses. In the case of injection administration, depending on the patient's weight, 1 μg / kg-3000 μg / kg or 3 μg / kg-1000 μg / kg may be administered in one or several divided doses. 【0102】 Also, as a non-limiting example, １７７ When Lu is used, the conjugate may be administered in a single dose to humans in the range of approximately 0.1 to 50 GBq, preferably approximately 2 to 10 GBq, more preferably 3 to 8 GBq, and even more preferably 4 to 7.4 GBq. Furthermore, as a non-limiting example, １７７ When using Lu, the dosage in humans may be 10 to 300 MBq / kg / dosage, preferably 30 to 150 MBq / kg / dosage, and more preferably 50 to 120 MBq / kg / dosage. Furthermore, as a non-limiting example, ２２５ When Ac is used, the conjugate may be administered in a single dose to adults in humans at a dose of 0.01 to 20 MBq / dose, preferably 0.05 to 15 MBq / dose. Furthermore, as a non-limiting example, ２２５When using Ac, the conjugate may be administered to humans at a dose of 5 to 300 kBq / kg / dose, preferably 10 to 250 kBq / kg / dose, and more preferably 20 to 150 kBq / kg / dose, based on body weight. 【0103】 In one embodiment, the present invention relates to a method for preventing or treating CLDN18.2-related diseases by administering the conjugate of the present invention (including pharmaceutically acceptable salts, isomers, or solvates thereof). Not limited thereto, the therapeutic method of the present invention includes the step of administering the conjugate of the present invention to a target. The target and method of administration are the same as those described in the "Pharmaceutical Composition" section. Also not limited thereto, the therapeutic method of the present invention includes the step of administering the conjugate of the present invention to a target area (affected area) with the aim of delivering the pharmacoactive component of the therapeutic method to any target area (affected area) using the conjugate of the present invention. 【0104】 In one embodiment, the present invention relates to the use of the conjugate of the present invention or a pharmaceutically acceptable salt thereof for the prevention or treatment of CLDN18.2-related diseases. In one embodiment, the present invention relates to the use of the conjugate of the present invention or a pharmaceutically acceptable salt thereof for the manufacture of a pharmaceutical composition for the prevention or treatment of CLDN18.2-related diseases. In one embodiment, the present invention relates to the use of the conjugate of the present invention or a pharmaceutically acceptable salt thereof as a pharmaceutical composition for the prevention or treatment of CLDN18.2-related diseases. In one embodiment, the present invention relates to the conjugate of the present invention or a pharmaceutically acceptable salt thereof for use in a method for preventing or treating CLDN18.2-related diseases. In one embodiment, the present invention relates to the conjugate of the present invention or a pharmaceutically acceptable salt thereof for use as a pharmaceutical composition for the prevention or treatment of CLDN18.2-related diseases. 【0105】Diagnostic Compositions and Imaging Agents The present invention also relates to a diagnostic composition for diagnosing CLDN18.2-related disease, comprising the peptide, conjugate, or pharmaceutically acceptable salt thereof of the present invention. The peptide and conjugate of the present invention may also be used as a diagnostic composition for CLDN18.2-related disease. The diagnostic agent may be a detection agent for diagnosing whether or not a person has CLDN18.2-related disease, a detection agent for diagnosing the severity of the disease, or a detection agent for diagnosing a poor prognosis of the disease. When used as a detection agent, the conjugate may be detectably labeled, a conjugate containing a detectable payload, or a conjugate containing a known imaging agent as a payload. In one embodiment, the present invention may include an imaging agent comprising a conjugate. The imaging agent may also be used as a diagnostic composition. In one embodiment, the diagnostic composition is an imaging agent. In this specification, “imaging agent” means a compound having one or more properties that make it possible to directly or indirectly detect its presence and / or location, enabling diagnostic imaging. Examples of such imaging agents include proteins, peptides, medium-sized compounds, small-sized compounds, and radioisotopes themselves, all incorporating a labeling moiety that enables detection. 【0106】 The label that enables detection can be a radioactive isotope (which may be bound to a chelating agent), a gold colloid, a nanoparticle such as a quantum dot, etc. The conjugate of the present invention has CLDN18.2 binding activity. For this reason, for example, by creating a peptide related to the labeled conjugate, administering it to a subject, and detecting it, the expression status of CLDN18.2 in the subject can be detected, thereby enabling the detection of the severity of CLDN18.2-related diseases. In addition, in an immunoassay, the peptide can be labeled with biotin and then detected by binding it to avidin or streptavidin labeled with an enzyme, etc. 【0107】Among immunoassays, the ELISA method using enzyme labeling is preferred because it allows for simple and rapid measurement of antigens. For example, an antibody is immobilized on a solid support, a sample is added and reacted, and then the labeled peptide is added and reacted. After washing, the mixture reacts with an enzyme substrate, develops color, and the absorbance is measured to detect the severity of CLDN18.2-related disease. After reacting the antibody immobilized on the solid support with the sample, the unlabeled peptide may be added, and an antibody against the peptide, which has been enzyme-labeled, may be added further. The antibody may be immobilized on the surface of the solid support or internally. 【0108】 The enzyme substrate can be 3,3'-diaminobenzidine (DAB), 3,3',5,5'-tetramethylbenzidine (TMB), o-phenylenediamine (OPD), etc., if the enzyme is a peroxidase, and p-nitrophenyl phosphate (pNPP), etc., if the enzyme is an alkaline phosphatase. In this specification, the "solid phase support" is not particularly limited as long as it is a support that can immobilize antibodies, and examples include microtiter plates made of glass, metal, or resin, substrates, beads, nitrocellulose membranes, nylon membranes, PVDF membranes, etc., and the target substance can be immobilized on these solid phase supports according to known methods. 【0109】Furthermore, in this specification, diagnostic imaging includes imaging by immunohistochemistry, immunofluorescence staining, etc., optical imaging such as positron emission tomography (PET, including PET-CT), single-photon emission computed tomography (SPECT), and non-invasive (molecular) diagnostic imaging including magnetic resonance imaging (MRI), iron oxide nanoparticles, and carbon-coated iron-cobalt nanoparticles. The imaging agent of the present invention can be used in any diagnostic imaging by selecting a label portion that enables detection. Preferably, it is an imaging agent for use in optical imaging such as PET, PET-CT, or SPECT. In one embodiment, the present invention relates to a radioactive ligand imaging agent used in positron emission tomography, comprising the conjugate of the present invention. The Cu-labeled conjugate of the present invention (for example) ６４ The Cu-labeled compound is administered to humans for PET diagnosis, and the administered activity may be in the range of 10 to 1000 MBq / administration, preferably 50 to 600 MBq / administration, and more preferably 100 to 400 MBq / administration. 【0110】 The present invention relates to a diagnostic kit comprising the conjugate of the present invention. The diagnostic kit comprises reagents and equipment necessary for the above detection (not limited to, any or all of the peptide or conjugate of the present invention, antibodies, solid support, buffer, enzyme reaction stop solution, microplate reader, etc.). 【0111】The present invention relates to a method for diagnosing CLDN18.2-related diseases using the conjugate of the present invention. The "diagnostic method" includes in vivo or in vitro diagnostic methods. Not limited to the present invention, the method includes the step of administering the conjugate of the present invention to a subject or a sample obtained from a subject. Not limited to the present invention, the method includes the step of administering the conjugate of the present invention to a subject or a sample obtained from a subject and detecting the binding of the peptide or conjugate of the present invention to CLDN18.2. The subjects and methods of administration are the same as those described in the "Pharmaceutical Composition" section. The "sample obtained from a subject" includes, for example, blood, urine, stool, tears, nasal secretions, tissue sections, etc. 【0112】 The present invention also relates to a method for detecting diseases using the conjugate of the present invention. Disease detection can be performed, for example, by medical technologists, researchers, etc., other than physicians, in research institutions (including educational institutions such as universities), companies, etc. In one embodiment, the disease detection method does not involve medical procedures. Preferably, it is a diagnostic method using PET, PET-CT, or SPECT. The present invention relates to the use of the conjugate of the present invention for the diagnosis of CLDN18.2-related diseases. The present invention relates to the use of the conjugate of the present invention for the manufacture of a diagnostic composition for the diagnosis of CLDN18.2-related diseases. The present invention relates to the use of the conjugate of the present invention as a diagnostic composition for the diagnosis of CLDN18.2-related diseases. The present invention relates to the conjugate of the present invention for use in a method for diagnosing CLDN18.2-related diseases or symptoms. The present invention relates to the conjugate of the present invention for use as a diagnostic composition for diagnosing CLDN18.2-related diseases or symptoms. The present invention relates to a tester containing the conjugate of the present invention. The present invention relates to a diagnostic or detection tester that includes the conjugate of the present invention. 【0113】In one embodiment, the present invention relates to a method for theranotics, comprising the steps of (1) identifying a subject in which expression of CLDN18.2 has been confirmed, and (2) administering a radioisotope-labeled peptide to the subject for treatment. (1) The step of identifying a subject in which expression of CLDN18.2 has been confirmed is a Cu-labeled conjugate (e.g. ６４ (2) The step of administering a radioisotope-labeled peptide to treat the tumor includes an Ac-labeled conjugate (for example, ２２５ This includes administering an Ac-labeled conjugate. In other words, it can be appropriately administered to patients in whom accumulation of the conjugate in the tumor has been confirmed during diagnosis. 【0114】 Research Compositions The present invention also relates to research compositions comprising the conjugate of the present invention. "Research compositions" include those used by researchers, engineers, students, doctors, etc., in research institutions (including educational institutions such as universities), companies, hospitals, etc. The research compositions can be used, for example, for the detection of CLDN18.2, or for the detection of CLDN18.2-related diseases or symptoms. 【0115】 In this specification, the carrier for immobilizing the conjugate is not particularly limited and includes, for example, microtiter plates made of lath, metal, or resin, substrates, beads, nitrocellulose membranes, nylon membranes, PVDF membranes, and the like. 【0116】The present invention includes a method for detecting CLDN18.2 using the conjugate of the present invention. The “detection method” includes in vivo or in vitro detection methods. Not limited to, the method of the present invention includes the step of administering the conjugate of the present invention to a subject or a sample obtained from a subject. Not limited to, the method of the present invention includes the step of administering the conjugate of the present invention to a subject or a sample obtained from a subject and detecting the binding of the conjugate of the present invention to CLDN18.2. The subject to administration and the method of administration are the same as those described in the “Pharmaceutical Composition” section. The “sample obtained from a subject” includes, for example, blood, urine, stool, tears, nasal secretions, tissue sections, etc. The present invention also includes the use of the conjugate of the present invention for the detection of CLDN18.2. The present invention relates to a diagnostic or detection kit comprising the conjugate of the present invention. The diagnostic or detection kit comprises reagents and equipment necessary for the above detection (not limited to, any or all of the peptide, antibody, solid support, buffer, enzyme reaction stop solution, microplate reader, etc. of the present invention). In one embodiment, the present invention includes a method for delivering a payload relating to the conjugate of the present invention to tissue expressing CLDN18.2 using the conjugate of the present invention. Non-limitingly, the method of the present invention includes the steps of producing the conjugate of the present invention and administering the peptide to a target. The target of administration and the method of administration are the same as those described in the "Pharmaceutical Compositions" section. Matters described in other sections also apply to this section unless otherwise specified. 【0117】 7. Test Method The present invention also relates to a method for testing a peptide conjugate or a pharmaceutically acceptable salt thereof for testing at least one of the following: a) solubility in a solvent; b) CLDN18.2 binding activity; c) toxicity to cells and / or tissues; or d) toxicity to experimental animals, wherein the peptide conjugate or the pharmaceutically acceptable salt thereof is the conjugate or the pharmaceutically acceptable salt thereof of the present invention. 【0118】The present invention also relates to a method for testing a conjugate, wherein the conjugate is the conjugate of the present invention, and the method is the method for testing the conjugate for testing at least one of the following: a) solubility in a solvent, b) CLDN18.2 binding activity, c) toxicity to cells and / or tissues, or d) toxicity to experimental animals. 【0119】"Solubility in solvents" can be measured using known methods. The solvent used for measuring solubility is not limited and can be freely selected according to the purpose. Furthermore, the method for measuring solubility can be appropriately selected according to the type of solvent. Non-limited, this may refer to the solubility of the conjugate when dissolved in known solvents such as water, glycerol, PBS, and DMSO. "CLDN18.2 binding activity" can be measured, for example, as described in "2. Peptides," etc. "Toxicity to cells and / or tissues" can be measured using known methods. For example, a test for toxicity to cells and / or tissues may be a known toxicity evaluation test using cells and / or tissues, and may be performed in vitro. The cells and / or tissues may be those typically used in toxicity evaluation tests for pharmaceuticals, and are not limited to those used in such tests. "Toxicity to experimental animals" can be measured using known methods. For example, laboratory animals are not particularly limited as long as they are commonly used, but examples include mice, rats, guinea pigs, gerbils, hamsters, ferrets, rabbits, dogs, cats, pigs, goats, horses, cattle, birds (e.g., chickens, quail, etc.), monkeys, and primates other than humans (e.g., cynomolgus macaques, marmosets, rhesus macaques, etc.). Furthermore, the toxicity evaluation tests mentioned above are not limited, but may be safety tests that are normally performed in non-clinical trials of pharmaceuticals, and examples include general toxicity tests (single-dose toxicity tests / repeated-dose toxicity tests), genotoxicity tests (Ames tests / chromosomal aberration tests / in vitro micronucleus tests), carcinogenicity tests, reproductive and developmental toxicity tests (ICH-I, II, III), topical irritation tests (eye irritation tests, skin irritation tests, etc.), other toxicity tests (skin sensitization tests, phototoxicity tests, antigenicity tests), and chemical analysis / bioanalysis (TK / PK). Unless otherwise specified, matters described in other sections also apply to this section. 【0120】8. Combined Use The conjugate of the present invention may be used in combination with other agents for the prevention or treatment of CLDN18.2-related diseases or symptoms. In one embodiment, the present invention relates to a combination of the conjugate and other agents for the prevention or treatment of CLDN18.2-related diseases or symptoms. The conjugate and other agents for the prevention or treatment of CLDN18.2-related diseases or symptoms may be administered simultaneously or sequentially. Preferably, the conjugate and other agents for the prevention or treatment of CLDN18.2-related diseases or symptoms are administered in such a manner that an additive effect, preferably a synergistic effect, is obtained. When administered sequentially, the order of administration does not matter. When administered sequentially, it is preferable, non-limitingly, to take both within 2 hours, 1 hour, 30 minutes, 20 minutes, 15 minutes, 10 minutes, or 5 minutes. Matters described in other sections also apply to this section unless otherwise specified. As a non-limiting example, zolbetuximab and the aforementioned conjugate may be used in combination for unresectable advanced or recurrent gastric cancer in CLDN18.2-positive (HER2-negative) patients. 【0121】 The present invention will be described in more detail below with reference to examples, but the present invention is not limited thereto. Those skilled in the art can easily modify and change the present invention based on the description herein, and such modifications fall within the technical scope of the present invention. The compound names shown in the following reference examples and examples do not necessarily follow IUPAC nomenclature. Abbreviations may be used for simplification of the description, but these abbreviations are as described above. 【0122】 The raw materials, building blocks, reagents, acids, bases, solid-phase resins, and solvents used in the chemical synthesis of the compounds were either commercially available or synthesized using organic chemical methods, as otherwise stated. Amino acids containing protecting groups were also commercially available. Peptide residues were counted starting with the ClAc-modated amino acid residue as the first residue, followed by the second, third, and so on towards the resin. Common amino acids used are listed below, with side-chain protecting groups indicated in parentheses. 【0123】Fmoc-Ile-OH; Fmoc-Leu-OH; Fmoc-Ser(Trt)-OH; Fmoc-Ser(tBu)-OH; Fmoc-His(Boc)-OH; Fmoc-Pro-OH; Fmoc-Asp(OMpe)-OH; Fmoc-Gln(Trt)-OH; Fmoc-Glu(tBu)-OH; Fmoc-Y(tBu)-OH; Fmoc-Gly-OH; Fmoc-Cys(Trt)-OH; Boc-Phe-OH; Fmoc-Lys(Boc)-OH. Also, for non-natural amino acids, the following and those described in the abbreviations were used. Fmoc-3FPeG-OH; Fmoc-3Py-OH; Fmoc-3Py5CON-OH; Fmoc-3Py6CON-OH; Fmoc-3Py6Et-OH; Fmoc-3Py6Me-OH; Fmoc-3Py6mor-OH; Fmoc-3Py6NH2(Boc)-OH; Fmoc-3Py6NHaa(tBu)-OH; Fmoc-3Py6O4pip1Ac-OH; Fmoc-3Py6O4thp-OH; Fmoc-3Py6OMe-OH; Fmoc-3Py6pipz4Ac-OH; Fmoc-4Py-OH; Fmoc-4Py3CON-OH; Fmoc-4Pyz-OH; Fmoc-4Pyz1Me-OH; Fmoc-5Pyrm-OH; Fmoc-AcaeG-OH; Fmoc-AcapG-OH; Fmoc-aMeC(Mmt)-OH; Fmoc-Atp-OH; Fmoc-bA2SMe-OH; Fmoc-PEG12c-OH; Boc-PEG12c-OH; Fmoc-Cba-OH; Fmoc-Cbg-OH; Fmoc-Cha-OH; Fmoc-CmG(Trt)-OH; Fmoc-CmmG(Trt)-OH; Fmoc-CmpG(Trt)-OH; Fmoc-da-OH; Fmoc-Dab(Boc)-OH; Fmoc-dd(Allyl)-OH; Fmoc-ddab(Boc)-OH; Fmoc-ddab(Alloc)-OH; Fmoc-ddap(Boc)-OH; Fmoc-df4COO(tBu)-OH; Fmoc-dhgl(tBu)-OH; Fmoc-dk(Boc)-OH; Fmoc-dk(Alloc)-OH; Alloc-dk(Fmoc)-OH;Fmoc-dkAc-OH; Fmoc-dkCOpipzaa(tBu)-OH; Fmoc-dn(Trt)-OH; Fmoc-dorn(Boc)-OH; Fmoc-dp-OH; Fmoc-dp4SNH2(Boc)-OH; Fmoc-dp4SNH2(Alloc)-OH; Fmoc-ds(Trt)-OH; Fmoc-dyae(Boc)-OH; Fmoc-EtG-OH; Fmoc-F3CON-OH; Fmoc-F4aao(tBu)-OH; Fmoc-F4C-OH; Fmoc-F4CON-OH; Fmoc-F4F-OH; Fmoc-F4Me-OH; Fmoc-F4OMe-OH; Fmoc-Gthp-OH; Fmoc-HeG(tBu)-OH; Fmoc-Hpr-OH; Fmoc-Hse(Trt)-OH; Fmoc-HseMe-OH; Fmoc-IMe-OH; Fmoc-K(Biotin)-OH; Fmoc-mCPeG-OH; Fmoc-Meda-OH; Fmoc-Medn(Trt)-OH; Fmoc-Meds(tBu)-OH; Fmoc-MeG-OH; Fmoc-MeopG-OH; Fmoc-MeS(Trt)-OH; Fmoc-Ndm-OH; Fmoc-Nmm-OH; Fmoc-oCPeG-OH; Fmoc-PeG-OH; Fmoc-PEG10c-OH; Fmoc-PEG4c-OH; Fmoc-PEG8c-OH; Fmoc-Tbg-OH; Fmoc-W7N-OH; Fmoc-Y3Me(tBu)-OH; Fmoc-Yae(Boc)-OH; Fmoc-YaeAc-OH; Fmoc-YaeCOpipzaa(tBu)-OH. ; 【0124】 The structure of chemically synthesized peptides was determined by calculating the molecular weight, considering the amino acids used according to the target sequence and the building blocks used as needed, and confirming this by ESI-MS(+) in mass spectrometry. "ESI-MS(+)" refers to electrospray ionization mass spectrometry performed in positive ion mode. The detected mass was reported in "m / z" units. Compounds with molecular weights greater than approximately 1000 were frequently detected as divalent or trivalent ions. 【0125】Example 1 Synthesis of Cyclic Peptides and Conjugates The chemically synthesized peptides were identified by retention time obtained using one of the following analytical methods (detection: UV wavelength 225 nm, Shimadzu Corporation ''SPD-M20A''). Analytical conditions A Column: Kinetex EVO C18 2.6 μm, 2.1 ID x 150 mm, 100 Å Mobile phase: A = 0.025% TFA water; B = 0.025% TFA CH ３ CN temperature: 60°C Flow rate: 0.5 mL / min Gradient: 20-60 / 7.15 min, 60-95 / 0.3 min. Analytical conditions B Column: Kinetex EVO C18 2.6 μm, 2.1 ID x 150 mm, 100 Å Mobile phase: A = 0.025% TFA in water; B = 0.025% TFA CH ３ CN temperature: 60°C, flow rate: 0.5 mL / min, gradient: 5-45 / 7.15 min, 45-95 / 0.3 min. Peptide chain extension in solid-phase resin was performed using the Fmoc method with commercially available resin as the starting material. Specifically, Sieber amide resin (Watanabe Chemical Industry Co., Ltd.) was used, starting with the removal of the Fmoc group, and the target peptide was synthesized by repeatedly introducing each Fmoc amino acid and deprotecting the Fmoc group. Unless otherwise specified, peptide chain extension was performed by automated synthesis, using CEM's Liberty Blue or Liberty Blue HT as the solid-phase synthesizer, and synthesis was performed according to the manufacturer's manual. When introducing each residue, double coupling, where the peptide coupling reaction is repeated twice, was performed as needed. On the other hand, the introduction of some amino acids was carried out by taking the resin from the automated synthesizer and performing the reaction using reagents prepared at the time of use (manual coupling). For example, approximately 4 equivalents of Fmoc amino acids, approximately 8 equivalents of DIC, and approximately 4 equivalents of Oxyma pure were added to a de-Fmoc-decomposed peptide chain supported on a solid-phase resin, and the mixture was shaken 1-2 times under one of the reaction conditions shown in the table below, after which the resin was washed with DMF. 【0126】 【0127】The Fmoc group was removed by, for example, the following method: The peptide chain, after the introduction of the Fmoc amino acid and supported on a solid-phase resin, was shaken 1-2 times under any of the conditions shown in the table below, and then the resin was washed with DMF. 【0128】 【0129】 Following the method described above, the introduction of each Fmoc amino acid and the deprotection of the Fmoc group were repeated to extend the peptide chain to the target peptide chain, after which the chloroacetyl group was introduced. The introduction method was one of the methods shown in the table below. After removing the Fmoc group from the solid-phase resin holding the Fmoc-protected peptide obtained in the previous step, a solution containing the following solvents, consisting of approximately 5 to 10 equivalents of chloroacetic acid, approximately 5 to 10 equivalents of a condensing agent, and approximately 5 to 10 equivalents of an additive, was added to the solid-phase resin and shaken at room temperature for 30 to 60 minutes. 【0130】 【0131】 Deprotection of the side chain and cleavage from the solid-phase resin are performed by applying one of the reagent cocktails (TFA / H) shown in the table below to the peptide bound to the resin after the introduction of the chloroacetyl group. ２ The mixture of O / TIS / DODT was added and shaken at room temperature for 30 to 360 minutes. 【0132】 【0133】 Subsequently, the reaction mixture was filtered and recovered from the frit. The filtrate was added to excess diisopropyl ether or a mixed solvent of diisopropyl ether and hexane or diethyl ether and hexane (e.g., 1 / 1, v / v) cooled to 0°C, resulting in a turbid precipitate. To obtain this precipitate solid, centrifugation was performed, and the supernatant was decanted. The obtained solid was washed with a small amount of diethyl ether cooled again to 0°C, and then dried under reduced pressure. The solid obtained above was used in the peptide cyclization reaction. The peptide cyclization reaction was carried out using DMSO or DMSO / H2O, with the final concentration of the peptide being 2 mM to 5 mM based on the number of moles of solid-phase resin used. ２ O, MeCN / H ２ O or DMSO / MeCN / H ２After dissolving in a mixed solvent of O, 5 to 35 equivalents of triethylamine were added, and the mixture was shaken at room temperature for 1 hour to overnight. The resulting reaction solution was concentrated under reduced pressure and then purified. The resulting residue was purified by reverse-phase preparative HPLC according to one of the methods in the table below. 【0134】 【0135】 The following shows the specific structures of the synthesized peptides and conjugates. Examples 1-1 to 1-19 relate to the synthesis of peptides. Example 1-1 Synthesis of Structure No. 35. 【0136】 【0137】The target peptide was synthesized using Sieber amide resin (Watanabe Chemical, 0.6 mmol / g, 1.25 g). A CEM Liberty Blue was used as the solid-phase synthesizer, and the synthesis was carried out according to the manufacturer's manual. To remove Fmoc from the solid-phase resin, 10% pyrrolidine (in DMF) was used, and the reaction was carried out once at 75°C for 3 minutes. To introduce each residue, 0.21 M Fmoc-AA (in DMF) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (4.2 equivalents / 8 equivalents / 4 equivalents) were used per equivalent of resin, and the reaction was carried out once at 75°C for 10 minutes. However, for the 7th residue, 0.21 M Fmoc-AA (in NMP) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (4.2 equivalents / 8 equivalents / 4 equivalents) was used, and for the 5th and 8th residues, the reaction was carried out twice at 75°C for 10 minutes each time. For the 13th residue, the reaction was carried out once at 50°C for 15 minutes each time. After the introduction of each residue, in order to remove the Fmoc group, 10% pyrrolidine (in DMF) was used on the solid-phase resin holding the Fmoc-protected peptide, and the reaction was carried out twice at room temperature for 5 minutes each time. For the 13th and 14th residues, a 10% pyrrolidine DMF solution was used, and the reaction was carried out once at 75°C for 3 minutes each time. The solid-phase resin containing the Fmoc-protected peptide obtained in the previous step was reacted with 10% pyrrolidine (in DMF) twice at room temperature for 5 minutes each time to remove the Fmoc group from the α-amino group. Chloroacetyl groups were then introduced by shaking with 0.188 M ClAcNHS (5 equivalents in DMF / DCM = 1 / 1) at room temperature for 60 minutes. To deprotect the side chains and cleave them from the solid-phase resin, the resin obtained after the chloroacetyl group introduction step was first washed once with DMF, DCM, and diethyl ether, and then dried under reduced pressure. Subsequently, a reaction cocktail (5 mL, TFA / H) was added to the reaction vessel. ２A mixture of O / TIS / DODT in a volume ratio of 90 / 2.5 / 2.5 / 5.0 was added and shaken at room temperature for 60 minutes. The reaction mixture was filtered and recovered through the frit. The solid resin remaining in the reaction vessel was shaken again with the cutting cocktail, the solution components were recovered through the frit and mixed with the aforementioned filtrate. This filtrate was divided into six parts and each was added to 30 mL of a mixed solvent of diethyl ether / hexane (1 / 1), resulting in a precipitate. This mixture was centrifuged and the solution was decanted. The obtained solid was washed again with diethyl ether and dried under reduced pressure. The obtained solid (peptide) was then used in the following cyclization reaction. The peptide was dissolved in water / acetonitrile (1 / 1) to a final concentration of 5 mM based on the number of moles of solid resin, and then 10 equivalents of triethylamine were added and the mixture was stirred at room temperature for 360 minutes to carry out the peptide cyclization reaction. The reaction was stopped by adding acetic acid to the reaction solution, and the reaction solution was concentrated under reduced pressure using Genevac EZ-II elite. The resulting crude product was purified under the following conditions (column: Waters XSelect® C18 5 μm 50 x 250 mm; mobile phase: A = 0.1% TFA (in water), B = 0.1% TFA (in MeCN); temperature: 50°C; gradient (%B): 0.0–0.0% over 5 minutes, 0.0–4.2% over 2 minutes, 4.2–28.6% over 3 minutes, 28.6–33.7% over 15.5 minutes, 33.7–60.0% over 1.5 minutes; flow rate: 18–18 mL / min over 5 minutes, 18–118 mL / min over 2 minutes, then 118 mL / min). The portion containing the target substance was collected and freeze-dried to obtain the target peptide. The purity of the target substance was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analysis conditions. The purity of the target substance was 98.4%. Analysis condition A: Retention time = 3.72 mins ESI-MS(+) Observed value m / z = 948.60 (M+2H) ２＋ 【0138】 Example 1-2 Synthesis of Structure No. 135. 【0139】 【0140】In 1.24 mL of DMF, the peptide SEQ ID No. 35 (25 mg) synthesized in Example 1-1 and DIPEA (28.9 mg) were dissolved, and then DOTA-NHS ester trifluoroacetate salt (27.2 mg, CAS: 170908-81-3) was added under ice cooling. The reaction mixture was stirred at room temperature for 60 minutes. The resulting reaction mixture was purified using the following conditions (column: Waters XSelect® C18 5μm 50x250mm; mobile phase: A = 0.1% TFA (in water), B = 0.1% TFA (in MeCN); temperature: 50°C; gradient (%B): 0.0–0.0% over 5 minutes, 0.0–4.2% over 2 minutes, 4.2–27.6% over 3 minutes, 27.6–32.7% over 15.5 minutes, 32.7–60.0% over 1.5 minutes; flow rate: 18–18 mL / min over 5 minutes, 18–118 mL / min over 2 minutes, then 118 mL / min). The portion containing the target substance was collected and freeze-dried to obtain the target peptide. The purity of the target substance was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analytical conditions. The purity of the target substance was 97.5%. Analysis conditions A: Retention time = 3.72 minutes; ESI-MS(+); Observed value m / z = 1141.80 (M+2H) ２＋ 【0141】 Examples 1-3 Synthesis of Structure No. 100. 【0142】 【0143】In 1.24 mL of DMF, the peptide SEQ ID No. 35 (25 mg) synthesized in Example 1-1 and DIPEA (28.9 mg) were dissolved, and then DOTA-NHS ester trifluoroacetate salt (27.2 mg) was added under ice cooling. The reaction mixture was stirred at room temperature for 150 minutes. In the reaction mixture, water (995 μL) in which lutetium(III) chloride hexahydrate (19 mg, CAS: 15230-79-2) and ammonium acetate (3 mg, CAS: 631-61-8) were dissolved was added. The reaction mixture was stirred at 90°C for 1 hour. The resulting reaction mixture was purified under the following conditions (column: Waters XSelect® C18 5μm 50x250mm; mobile phase: A = 1.0% AcOH (in water), B = 1.0% AcOH (in MeCN); temperature: 50°C; gradient (%B): 0.0–0.0% over 5 minutes, 0–1.1% over 0.1 minutes, 1.1–5.2% over 1.9 minutes, 5.2–30.7% over 3 minutes, 30.7–35.8% over 15.5 minutes, 35.8–60% over 1.5 minutes; flow rate: 18–18 mL / min over 5.1 minutes, 18–118 mL / min over 1.9 minutes, then 118 mL / min). The portion containing the target substance was collected and freeze-dried to obtain the target peptide. The purity of the target substance was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analysis conditions. The purity of the target substance was 99.7%. Analysis condition A: Retention time = 3.92 mins ESI-MS (+) Observed value m / z = 819.17 (M + 3H) ３＋ 【0144】 Examples 1-4 Synthesis of Structure No. 36. 【0145】 【0146】The target peptide was synthesized using Sieber amide resin (Watanabe Chemical, 0.6 mmol / g, 0.42 g). A CEM Liberty Blue was used as the solid-phase synthesizer, and the synthesis was carried out according to the manufacturer's manual. To remove Fmoc from the solid-phase resin, 10% pyrrolidine (in DMF) was used, and the reaction was carried out once for 1 minute at 90°C. To introduce each residue, 0.21 M Fmoc-AA (in DMF) / 1 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (4.2 equivalents / 8 equivalents / 4 equivalents) were used per equivalent of resin, and the reaction was carried out once for 3 minutes at 90°C. However, for residues 1, 3, 4, 5, 6, 7, and 9, 0.21 M Fmoc-AA (in NMP) / 1 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (4.2 equivalents / 8 equivalents / 4 equivalents) was used. However, for residue 5, the reaction was carried out twice at 75°C for 30 minutes each time. For residue 8, the reaction was carried out twice at 90°C for 3 minutes each time. For residues 2 and 4, the reaction was carried out once at 90°C for 10 minutes each time. For residue 13, the reaction was carried out once at 50°C for 15 minutes each time. After the introduction of each residue, in order to remove the Fmoc group, 10% pyrrolidine (in DMF) was used on the solid-phase resin holding the Fmoc-protected peptide, and the reaction was carried out twice at room temperature for 1 minute each time. For the 13th residue, a 10% pyrrolidine DMF solution was used, and the reaction was carried out at 90°C for 1 minute. The Fmoc group of the α-amino group was removed from the solid phase resin containing the Fmoc-protected peptide obtained in the previous step by reacting it twice with 10% pyrrolidine (in DMF) at room temperature for 1 minute each time. A chloroacetyl group was then introduced by shaking with 0.2 M ClAcNHS (10 equivalents in DMF / DCM = 1 / 1) at room temperature for 90 minutes. To deprotect the side chain and cleave it from the solid phase resin, the resin obtained after the chloroacetyl group introduction step was first washed once with DMF, DCM, and diethyl ether, and then dried under reduced pressure. Subsequently, a reaction cocktail (4 mL, TFA / H) was added to the reaction vessel containing the solid phase resin. ２A mixture of O / TIS / DODT in a volume ratio of 92.5 / 2.5 / 2.5 / 2.5 was added and shaken at room temperature for 90 minutes. The reaction mixture was filtered and recovered through the frit. The solid resin remaining in the reaction vessel was shaken again with the cutting cocktail, the solution components were recovered through the frit and mixed with the aforementioned filtrate. When this filtrate was added to 40 mL of a mixed solvent of diisopropyl ether / hexane (1 / 1), a precipitate formed. This mixture was centrifuged and the solution was decanted. The obtained solid was washed again with diethyl ether and dried under reduced pressure. The obtained solid (peptide) was then used in the following cyclization reaction. The peptide was dissolved in water / DMSO (1 / 9) to a final concentration of 5 mM based on the number of moles of solid resin, and then 10 equivalents of triethylamine were added and the peptide was cyclized by stirring at room temperature for 60 minutes. The reaction was stopped by adding acetic acid to the reaction solution, and the reaction solution was concentrated under reduced pressure using Genevac EZ-II elite. The resulting crude product was purified under the following conditions (column: Waters XSelect® C18 5 μm 50 x 250 mm; mobile phase: A = 0.1% TFA (in water), B = 0.1% TFA (in MeCN); temperature: 50°C; gradient (%B): 0.0–0.0% over 5 minutes, 0.0–4.2% over 2 minutes, 4.2–22.5% over 3 minutes, 22.5–27.6% over 15.5 minutes, 27.6–60% over 1.5 minutes; flow rate: 18–18 mL / min over 5.0 minutes, 18–118 mL / min over 2 minutes, then 118 mL / min). The portion containing the target substance was collected and freeze-dried to obtain the target peptide. The purity of the target substance was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analysis conditions. The purity of the target substance was 98.4%. Analysis condition B: Retention time = 5.14 mins ESI-MS(+) Observed value m / z = 890.02 (M+2H) ２＋ 【0147】 Examples 1-5 Synthesis of Structure No. 136. 【0148】 【0149】In 7.97 mL of DMF, the peptide SEQ ID No. 36 (160 mg) and DIPEA (186 mg) synthesized in Examples 1-4 were dissolved, and then DOTA-NHS ester trifluoroacetate salt (116 mg, CAS: 170908-81-3) was added under ice cooling. The reaction mixture was stirred at room temperature for 60 minutes. The resulting reaction mixture was purified using the following conditions (column: Waters XSelect® C18 5μm 50x250mm; mobile phase: A = 0.1% TFA (in water), B = 0.1% TFA (in MeCN); temperature: 50°C; gradient (%B): 0.0–0.0% over 5 minutes, 0.0–4.2% over 2 minutes, 4.2–20.5% over 3 minutes, 20.5–25.6% over 15.5 minutes, 25.6–60% over 1.5 minutes, 60–90% over 4 minutes; flow rate: 18 mL / min over 5 minutes, 18–118 mL / min over 2 minutes, then 118 mL / min). The portion containing the target substance was collected and freeze-dried to obtain the target peptide. The purity of the target substance was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analysis conditions. The purity of the target substance was 98.8%. Analysis condition B: Retention time = 5.06 mins ESI-MS(+) Observed value m / z = 1083.24 (M+2H) ２＋ 【0150】 Examples 1-6 Synthesis of Structure No. 40. 【0151】 【0152】The target peptide was synthesized using Sieber amide resin (Watanabe Chemical, 0.6 mmol / g, 0.42 g). A CEM Liberty Prime solid-phase synthesizer was used, and the synthesis was carried out according to the manufacturer's manual. To remove Fmoc from the solid-phase resin, 10% pyrrolidine (in DMF) was used, and the reaction was carried out once at 110°C for 1.5 minutes. To introduce each residue, 0.21 M Fmoc-AA (in DMF) / 2 M DIC (in DMF) / 0.25 M Oxyma pure (in DMF) (4.2 equivalents / 8 equivalents / 4 equivalents) were used per equivalent of resin, and the reaction was carried out once at 105°C for 2 minutes. However, for the third residue, 0.21 M Fmoc-AA (in NMP) / 2 M DIC (in DMF) / 0.25 M Oxyma pure (in DMF) (4.2 equivalents / 8 equivalents / 4 equivalents) was used, and for the fifth and eighth residues, the reaction was carried out twice at 90°C for 10 minutes each time. For the thirteenth residue, the reaction was carried out once at 50°C for 15 minutes each time. After the introduction of each residue, in order to remove the Fmoc group, 10% pyrrolidine (in DMF) was used on the solid-phase resin holding the Fmoc-protected peptide, and the reaction was carried out twice at room temperature for 1 minute each time. For the thirteenth residue, 4% pyrrolidine + 83 mM / Oxyma pure (in DMF) was used, and the reaction was carried out once at 110°C for 1.5 minutes each time. The solid-phase resin containing the Fmoc-protected peptide obtained in the previous step was reacted with 10% pyrrolidine (in DMF) twice at room temperature for 1 minute each time to remove the Fmoc group from the α-amino group. Chloroacetyl groups were then introduced by shaking with 0.125 M ClAcNHS (5 equivalents in DMF / DCM = 1 / 1) at room temperature for 60 minutes. To deprotect the side chains and cleave them from the solid-phase resin, the resin obtained after the chloroacetyl group introduction step was first washed once with DMF, DCM, and diethyl ether, and then dried under reduced pressure. Subsequently, a reaction cocktail (10 mL, TFA / H) was added to the reaction vessel containing the solid-phase resin. ２A mixture of O / TIS / DODT in a volume ratio of 90 / 2.5 / 2.5 / 5.0 was added and shaken at room temperature for 60 minutes. The reaction mixture was filtered and recovered through the frit. The solid resin remaining in the reaction vessel was shaken again with the cutting cocktail, the solution components were recovered through the frit and mixed with the aforementioned filtrate. This filtrate was divided into three parts and each was added to 30 mL of a mixed solvent of diisopropyl ether / hexane (1 / 1), resulting in a precipitate. This mixture was centrifuged and the solution was decanted. The resulting solid was washed again with diethyl ether and dried under reduced pressure. The resulting solid (peptide) was then used in the next cyclization reaction. The peptide was dissolved in water / acetonitrile (1 / 1) to a final concentration of 5 mM based on the number of moles of solid resin, and then 10 equivalents of triethylamine were added and the peptide was cyclized by stirring at room temperature for 300 minutes. The reaction was stopped by adding acetic acid to the reaction solution, and the reaction solution was concentrated under reduced pressure using Genevac EZ-II elite. The resulting crude product was purified under the following conditions (column: Waters XSelect® C18 5 μm 50 x 150 mm; mobile phase: A = 0.1% TFA (in water), B = 0.1% TFA (in MeCN); temperature: 40°C; gradient (%B): 5.0-5.0% over 2 minutes, 5.0-22.0% over 1 minute, 22.0-27.0% over 8 minutes, 27.0-60.0% over 1 minute; flow rate: 20-20 mL / min over 1 minute, 20-120 mL / min over 1 minute, then 120 mL / min). The portion containing the target substance was collected and freeze-dried to obtain the target peptide. The purity of the target substance was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analysis conditions. The purity of the target substance was 98.0%. Analysis condition B: Retention time = 5.22 mins ESI-MS (+) Observed value m / z = 947.02 (M + 2H) ２＋ 【0153】 Examples 1-7 Synthesis of Structure No. 170 【0154】 【0155】In 7.55 mL of DMF, the peptide SEQ ID No. 40 (160 mg) and DIPEA (176 mg) synthesized in Examples 1-6 were dissolved, and then DOTA-NHS ester trifluoroacetate salt (110 mg, CAS: 170908-81-3) was added under ice cooling. The reaction mixture was stirred at room temperature for 60 minutes. The resulting reaction mixture was purified using the following conditions (column: Waters XSelect® C18 5μm 50x250mm; mobile phase: A = 0.1% TFA (in water), B = 0.1% TFA (in MeCN); temperature: 50°C; gradient (%B): 0.0–0.0% over 5 minutes, 0.0–4.2% over 2 minutes, 4.2–20.5% over 3 minutes, 20.5–25.6% over 15.5 minutes, 25.6–60% over 1.5 minutes; flow rate: 18–18 mL / min over 5 minutes, 18–118 mL / min over 2 minutes, then 118 mL / min). The portion containing the target substance was collected and freeze-dried to obtain the target peptide. The purity of the target substance was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analytical conditions. The purity of the target substance was 97.8%. Analysis conditions B: Retention time = 5.11 minutes; ESI-MS(+); Observed values ​​m / z = 760, 59 (M+3H) ３＋ 【0156】 Example 1-8 Synthesis of Structure No. 41. 【0157】 【0158】The target peptide was synthesized using Sieber amide resin (Watanabe Chemical, 0.6 mmol / g, 0.21 g). A CEM Liberty Prime 2.0 was used as the solid-phase synthesizer, and the synthesis was carried out according to the manufacturer's manual. To remove Fmoc from the solid-phase resin, 10% pyrrolidine (in DMF) was used, and the reaction was carried out once for 1 minute at 110°C. To introduce each residue, 0.21 M Fmoc-AA (in DMF) / 2 M DIC (in DMF) / 0.25 M Oxyma pure (in DMF) (4.2 equivalents / 8 equivalents / 4 equivalents) were used per equivalent of resin, and the reaction was carried out once for 2 minutes at 105°C. However, for the 6th and 7th residues, 0.21 M Fmoc-AA (in NMP) / 2 M DIC (in DMF) / 0.25 M Oxyma pure (in DMF) (4.2 equivalents / 8 equivalents / 4 equivalents) was used, and for the 7th residue, the reaction was carried out once at 90°C for 10 minutes. For the 5th and 8th residues, the reaction was carried out twice at 90°C for 10 minutes each. For the 13th residue, the reaction was carried out once at 50°C for 15 minutes. After the introduction of each residue, in order to remove the Fmoc group, 10% pyrrolidine (in DMF) was used on the solid-phase resin holding the Fmoc-protected peptide, and the reaction was carried out twice at room temperature for 1 minute each. For the side chain of the 13th residue, 4% pyrrolidine + 83 mM / Oxyma pure (in DMF) was used, and the reaction was carried out once at 110°C for 1 minute each. The solid-phase resin containing the Fmoc-protected peptide obtained in the previous step was reacted with 10% pyrrolidine (in DMF) twice at room temperature for 1 minute each time to remove the Fmoc group from the α-amino group. Chloroacetyl groups were then introduced by shaking with 0.25 M ClAcNHS (10 equivalents in DMF / DCM = 1 / 1) at room temperature for 60 minutes. To deprotect the side chains and cleave them from the solid-phase resin, the resin obtained after the chloroacetyl group introduction step was first washed once with DMF, DCM, and diethyl ether, and then dried under reduced pressure. Subsequently, a reaction cocktail (5 mL, TFA / H) was added to the reaction vessel containing the solid-phase resin. ２A mixture of O / TIS / DODT in a volume ratio of 92.5 / 2.5 / 2.5 / 2.5 was added and shaken at room temperature for 30 minutes. The reaction solution was filtered and recovered through the frit. The solid resin remaining in the reaction vessel was shaken again with the cutting cocktail, the solution components were recovered through the frit and mixed with the aforementioned filtrate. When this filtrate was added to 40 mL of a mixed solvent of diethyl ether / hexane (1 / 1), a precipitate was formed. This mixture was centrifuged and the solution was decanted. The obtained solid was washed again with diethyl ether and dried under reduced pressure. The obtained solid (peptide) was then used in the following cyclization reaction. The peptide was dissolved in water / acetonitrile (1 / 1) to a final concentration of 5 mM based on the number of moles of solid resin, and then 20 equivalents of triethylamine were added and the peptide was cyclized by stirring at room temperature for 60 minutes. The reaction was stopped by adding acetic acid to the reaction solution, and the reaction solution was concentrated under reduced pressure using Genevac HT-12. The obtained crude product was purified using the following conditions (column: Waters XSelect® C18 5 μm 50 x 250 mm; mobile phase: A = 0.1% TFA (in water), B = 0.1% TFA (in MeCN); temperature: 50°C; gradient (%B): 0.0–0.0% over 5 minutes, 0.0–4.2% over 2 minutes, 4.2–21.5% over 3 minutes, 21.5–26.6% over 15.5 minutes, 26.6–60.0% over 1.5 minutes; 18–18 mL / min over 5 minutes, 18–118 mL / min over 2 minutes, then 118 mL / min). The portion containing the target substance was collected and freeze-dried to obtain the target peptide. The purity of the target substance was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analytical conditions. The purity of the target substance was 97.2%. Analysis conditions B: Retention time = 5.08 mins; ESI-MS(+); Observed value m / z = 961.18 (M+2H) ２＋ 【0159】 Examples 1-9 Synthesis of Structure No. 171 【0160】 【0161】In 0.931 mL of DMF, the peptide SEQ ID No. 41 (20 mg) and DIPEA (21.7 mg) synthesized in Examples 1-8 were dissolved, and then DOTA-NHS ester trifluoroacetate salt (13.6 mg, CAS: 170908-81-3) was added under ice cooling. The reaction mixture was stirred at room temperature for 60 minutes. The resulting reaction mixture was purified using the following conditions (column: Waters XSelect® C18 5μm 50x250mm; mobile phase: A = 0.1% TFA (in water), B = 0.1% TFA (in MeCN); temperature: 50°C; gradient (%B): 0.0–0.0% over 5 minutes, 0.0–4.2% over 2 minutes, 4.2–21.5% over 3 minutes, 21.5–26.6% over 15.5 minutes, 26.6–60% over 1.5 minutes; flow rate: 18–18 mL / min over 5 minutes, 18–118 mL / min over 2 minutes, then 118 mL / min). The portion containing the target substance was collected and freeze-dried to obtain the target peptide. The purity of the target substance was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analytical conditions. The purity of the target substance was 96.1%. Analysis conditions B: Retention time = 5.40 mins; ESI-MS(+); Observed value m / z = 769.88 (M+3H) ３＋ 【0162】 Example 1-10 Synthesis of Structure No. 120. 【0163】 【0164】The target peptide was synthesized using Sieber amide resin (Watanabe Chemical, 0.6 mmol / g, 0.33 g). A CEM Liberty Blue was used as the solid-phase synthesizer, and the synthesis was carried out according to the manufacturer's manual. To remove Fmoc from the solid-phase resin, 10% pyrrolidine (in DMF) was used, and the reaction was carried out once for 1 minute at 90°C. To introduce each residue, 0.21 M Fmoc-AA (in DMF) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (5.25 equivalents / 10 equivalents / 5 equivalents) were used per equivalent of resin, and the reaction was carried out once for 10 minutes at 90°C. However, for the first residue, 0.21 M Fmoc-AA (in DMF) / 0.5 M HATU (in DMF) / 1.0 M DIPEA (in DMF) (5.25 equivalents / 5 equivalents / 10 equivalents) was used, and the reaction was carried out once at room temperature for 60 minutes. For the third residue, 0.21 M Fmoc-AA (in NMP) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (5.25 equivalents / 10 equivalents / 5 equivalents) was used, and the reaction was carried out once at 90°C for 3 minutes. For the 5th residue, 0.21 M Fmoc-AA (in NMP) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (5.25 equivalents / 10 equivalents / 5 equivalents) was used, and the reaction was carried out twice for 10 minutes at 90°C. For the 7th and 9th residues, 0.21 M Fmoc-AA (in NMP) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (5.25 equivalents / 10 equivalents / 5 equivalents) was used, and the reaction was carried out once for 10 minutes at 90°C. For the 8th and 10th residues, the reaction was carried out twice for 10 minutes at 90°C. For the 6th residue, the reaction was carried out once for 30 minutes at 75°C. For the 13th residue, the reaction was carried out once for 15 minutes at 50°C. To remove the Fmoc group after introducing each residue, the solid-phase resin holding the Fmoc-protected peptide was reacted twice for 1 minute at room temperature using a 10% pyrrolidine DMF solution. For residues 3, 4, 6, 7, 9, 11, and 12, a reaction was carried out once at 50°C for 1.5 minutes using 4% pyrrolidine + 83 mM / Oxyma pure (in DMF). For residue 13, a reaction was carried out once at 90°C for 1 minute using a 10% pyrrolidine DMF solution.To the solid-phase resin containing the Fmoc-protected peptide obtained in the previous step, tetrakis(triphenylphosphine)palladium (0) (CAS: 14221-01-3) / phenylsilane (CAS: 694-53-1) (0.2 equivalents / 10 equivalents) and DCM (8 mL) were added and the mixture was reacted at room temperature for 90 minutes. The resin was washed with DCM and DMF. Subsequently, tert-butyl(3-aminopropyl)carbamate (10 equivalents, CAS: 75178-96-0) and PyAOP / DIPEA (10 equivalents / 10 equivalents in 12 mL of DMF) were added and the mixture was reacted at room temperature for 2 hours. The Fmoc groups of the α-amino groups were removed from the solid-phase resin containing the Fmoc-protected peptide obtained in the previous step by reacting it twice with 10% pyrrolidine (in DMF) at room temperature for 3 minutes each time. Chloroacetyl groups were further introduced by shaking with 0.2 M ClAcNHS (10 equivalents in DMF) at room temperature for 60 minutes. To deprotect the side chains and cleave them from the solid phase resin, the resin obtained after the chloroacetyl group introduction step was first washed once with DMF, DCM, and diethyl ether, and then dried under reduced pressure. Subsequently, a reaction cocktail (10 mL, TFA / H) was added to the reaction vessel. ２A mixture of O / TIS / DODT in a volume ratio of 92.5 / 2.5 / 2.5 / 2.5 was added and shaken at room temperature for 90 minutes. The reaction mixture was filtered and recovered through the frit. The solid resin remaining in the reaction vessel was shaken again with the cutting cocktail, the solution components were recovered through the frit and mixed with the aforementioned filtrate. This filtrate was divided into two parts and each was added to 40 mL of a mixed solvent of diisopropyl ether / hexane (1 / 1), resulting in a precipitate. This mixture was centrifuged and the solution was decanted. The obtained solid was washed again with diethyl ether and dried under reduced pressure. The obtained solid (peptide) was then used in the following cyclization reaction. The peptide was dissolved in DMSO / water / acetonitrile (1 / 1 / 1) to a final concentration of 2 mM based on the number of moles of solid resin, and then 10 equivalents of triethylamine were added and the mixture was stirred at room temperature for 60 minutes to carry out the peptide cyclization reaction. The reaction was stopped by adding acetic acid to the reaction solution, and the reaction solution was concentrated under reduced pressure using Genevac HT-12. The resulting crude product was purified under the following conditions (column: Waters XSelect® C18 5 μm 50 x 250 mm; mobile phase: A = 0.1% TFA (in water), B = 0.1% TFA (in MeCN); temperature: 50°C; gradient (%B): 0.0–0.0% over 5 minutes, 0.0–4.2% over 2 minutes, 4.2–23.6% over 3 minutes, 23.6–28.6% over 15.5 minutes, 28.6–60% over 1.5 minutes; flow rate: 18–18 mL / min over 5 minutes, 18–118 mL / min over 2 minutes, then 118 mL / min). The portion containing the target substance was collected and freeze-dried to obtain the target peptide. The obtained cyclic peptide was used as a starting material and subjected to the same reaction and purification conditions as in Examples 1-3 to obtain the target peptide. The purity of the target product was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analytical conditions. The purity of the target product was 99.9%. Analytical condition B: Retention time = 6.04 mins ESI-MS (+) Observed value m / z = 794.19 (M + 3H) ３＋ 【0165】 Example 1-11 Synthesis of Structure No. 134. 【0166】 【0167】 The target peptide was synthesized using Sieber amide resin (Watanabe Chemical, 0.6 mmol / g, 0.42 g). A CEM Liberty Blue was used as the solid-phase synthesizer, and the synthesis was carried out according to the manufacturer's manual. To remove Fmoc from the solid-phase resin, 10% pyrrolidine (in DMF) was used, and the reaction was carried out once for 1 minute at 90°C. To introduce each residue, 0.21 M Fmoc-AA (in DMF) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (4.2 equivalents / 8 equivalents / 4 equivalents) were used per equivalent of resin, and the reaction was carried out once for 3 minutes at 90°C. However, for residues 3 and 7, the reaction was carried out once at 90°C for 3 minutes using 0.21 M Fmoc-AA (in NMP) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (4.2 equivalents / 8 equivalents / 4 equivalents). For residues 5 and 8, the reaction was carried out twice at 90°C for 10 minutes. For residue 13, the reaction was carried out once at 50°C for 15 minutes. After the introduction of each residue, in order to remove the Fmoc group, the solid phase resin holding the Fmoc-protected peptide was reacted twice at room temperature for 1 minute using a 10% pyrrolidine DMF solution. For residue 13, the reaction was carried out once at 90°C for 1 minute using 4% pyrrolidine + 83 mM Oxyma pure (in DMF). To the solid-phase resin containing the peptide obtained in the previous step, Fmoc-OSu (5 equivalents) and DCM (10 mL) were added and reacted at room temperature for 1 hour, then the resin was washed with DMF. Tetrakis(triphenylphosphine)palladium (0) / phenylsilane (0.2 equivalents / 10 equivalents), 2% HFIP / DCM (10 mL) were added and reacted at room temperature for 60 minutes. The resin was washed with DCM and DMF. Subsequently, ddotaga(Mpe) ４-OH (3.2 equivalents) and HATU / DIPEA (3 equivalents / 5 equivalents in 9 mL of DMF) were added and the mixture was reacted at room temperature for 1 hour. The Fmoc group of the α-amino group was removed from the solid phase resin containing the Fmoc-protected peptide obtained in the previous step by reacting it once with 10% pyrrolidine (in DMF) at room temperature for 10 minutes. Chloroacetyl groups were then introduced by shaking with 0.31 M ClAcNHS (10 equivalents in DMF) at room temperature for 60 minutes. To deprotect the side chains and cleave them from the solid phase resin, the resin obtained after the chloroacetyl group introduction step was first washed once with DMF, DCM, and diethyl ether, and then dried under reduced pressure. Reagent cocktail (12 mL, TFA / H ２A mixture of O / TIS / DODT in a volume ratio of 90 / 2.5 / 2.5 / 5.0 was added and shaken at room temperature for 120 minutes. The reaction solution was filtered and recovered through the frit. The solid resin remaining in the reaction vessel was shaken again with the cutting cocktail, the solution components were recovered through the frit and mixed with the aforementioned filtrate. This filtrate was divided into two parts and each was added to 30 mL of a mixed solvent of diisopropyl ether / hexane (1 / 1), resulting in a precipitate. This mixture was centrifuged and the solution was decanted. The obtained solid was washed again with diethyl ether and dried under reduced pressure. The obtained solid (peptide) was then used in the next cyclization reaction. The peptide was dissolved in 1% triethylamine aqueous solution / acetonitrile (1 / 1) to a final concentration of 5 mM based on the number of moles of solid resin, and the peptide was cyclized by stirring at room temperature for 60 minutes. The reaction was stopped by adding acetic acid to the reaction solution, and the reaction solution was concentrated under reduced pressure using Genevac EZ-II elite. The resulting crude product was purified under the following conditions (column: Waters XSelect® C18 5 μm 50 x 250 mm; mobile phase: A = 0.1% TFA (in water), B = 0.1% TFA (in MeCN); temperature: 50°C; gradient (%B): 0.0–0.0% over 5.0 minutes, 0.0–4.2% over 2 minutes, 4.2–22.5% over 3 minutes, 22.5–27.6% over 15.5 minutes, 27.6–60% over 1.5 minutes, 60–90% over 4.0 minutes; flow rate: 18–18 mL / min over 5.0 minutes, 18–118 mL / min over 2 minutes, then 118 mL / min). The portion containing the target substance was collected, freeze-dried, and re-purified under the following conditions (column: Waters XSelect® C18 5μm 30x150mm; mobile phase: A = 1.0% AcOH (in water), B = 1.0% AcOH (in MeCN); temperature: 40°C; gradient (%B): 5-22% over 3 minutes, 22-27% over 8 minutes, 27-60% over 1 minute; flow rate: 45 mL / min). The portion containing the target substance was collected and freeze-dried. The obtained cyclic peptide (35 mg) was dissolved in DMF (1.24 mL), and then water (995 μL) containing dissolved lutetium(III) chloride hexahydrate (10 mg) and ammonium acetate (2 mg) was added. The reaction mixture was stirred at 90°C for 1 hour.The resulting reaction mixture was purified using the following conditions (column: Waters XSelect® C18 5μm 50x150mm; mobile phase: A = 0.1% TFA (in water), B = 0.1% TFA (in MeCN); temperature: 50°C; gradient (%B): 0-0% over 5 minutes, 0-4.2% over 2 minutes, 4.2-23.6% over 3 minutes, 23.6-28.6% over 15.5 minutes, 28.6-60% over 1.5 minutes; flow rate: 18-18 mL / min over 5 minutes, 18-118 mL / min over 2 minutes, then 118 mL / min). The portion containing the target substance was collected and freeze-dried to obtain the target peptide. The purity of the target substance was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analytical conditions. The purity of the target substance was 99.0%. Analytical conditions A: Retention time = 3.27 minutes, ESI-MS(+), Observed value m / z = 1219.29 (M+2H). ２＋ 【0168】 Example 1-12 Synthesis of Structure No. 184. 【0169】 【0170】The target peptide was synthesized using Sieber amide resin (Watanabe Chemical, 0.6 mmol / g, 0.10 g). A CEM Liberty Blue was used as the solid-phase synthesizer, and the synthesis was carried out according to the manufacturer's manual. To remove Fmoc from the solid-phase resin, 10% pyrrolidine (in DMF) was used, and the reaction was carried out once for 1 minute at 110°C. For the introduction of each residue, for residues 2, 3, 5, 6, 8, 12, and 16 per equivalent of resin, 0.21 M Fmoc-AA (in NMP) / 2.0 M DIC (in DMF) / 0.25 M Oxyma pure (in DMF) (4.2 equivalents / 16 equivalents / 6 equivalents) was used, and the reaction was carried out once for 90 seconds at 105°C. For the fourth residue, a mixture of 0.21 M Fmoc-AA (in NMP) / 2.0 M DIC (in DMF) / 0.25 M Oxyma pure (in DMF) (4.2 equivalents / 16 equivalents / 6 equivalents) was used, and the reaction was carried out twice at 90°C for 10 minutes each time. Similarly, for the seventh residue, a mixture of 0.21 M Fmoc-AA (in DMF) / 2.0 M DIC (in DMF) / 0.25 M Oxyma pure (in DMF) (4.2 equivalents / 16 equivalents / 6 equivalents) was used, and the reaction was carried out twice at 90°C for 10 minutes each time. For the 13th residue, a reaction was carried out once at 50°C for 15 minutes using 0.21 M Fmoc-AA (in DMF) / 2.0 M DIC (in DMF) / 0.25 M Oxyma pure (in DMF) (4.2 equivalents / 16 equivalents / 6 equivalents). For the remaining residues, a reaction was carried out once at 105°C for 90 seconds using 0.21 M Fmoc-AA (in DMF) / 2.0 M DIC (in DMF) / 0.25 M Oxyma pure (in DMF) (4.2 equivalents / 16 equivalents / 6 equivalents). After introducing each residue, in order to remove the Fmoc group, a reaction was carried out once at 50°C for 90 seconds using 10% pyrrolidine (in DMF) on the solid-phase resin holding the Fmoc-protected peptide. For residues 3 and 6, the reaction was carried out twice at room temperature for 90 seconds each time. For residues 12, 13, 14, 15, and 16, 4% pyrrolidine + 83 mM / Oxyma pure (in DMF) was used, and the reaction was carried out once at 110°C for 1 minute.The solid-phase resin containing the Fmoc-protected peptide obtained in the previous step was reacted once with 10% pyrrolidine (in DMF) at 50°C for 90 seconds to remove the Fmoc group from the α-amino group. Chloroacetyl groups were then introduced by shaking with 0.20 M ClAcNHS (10 equivalents in DMF) at room temperature for 80 minutes. To deprotect the side chains and cleave them from the solid-phase resin, the resin obtained after the chloroacetyl group introduction step was first washed once with DMF, DCM, and diethyl ether, and then dried under reduced pressure. Subsequently, a reaction mixture (2.5 mL, TFA / H) was added to the reaction vessel. ２A mixture of O / TIS / DODT in a volume ratio of 90.0 / 2.5 / 2.5 / 5.0 was added and shaken at room temperature for 40 minutes. The reaction mixture was filtered and recovered through the frit. The solid resin remaining in the reaction vessel was shaken again with the cutting cocktail, the solution components were recovered through the frit and mixed with the aforementioned filtrate. When this filtrate was added to 35 mL of a mixed solvent of diisopropyl ether / hexane (1 / 1), a precipitate formed. This mixture was centrifuged and the solution was decanted. The obtained solid was washed again with diethyl ether and dried under reduced pressure. The obtained solid (peptide) was then used in the following cyclization reaction. The peptide was dissolved in DMSO / water / acetonitrile (1 / 2 / 2) to a final concentration of 5 mM based on the number of moles of solid resin, and then 10 equivalents of triethylamine were added and the mixture was stirred at room temperature for 14 hours to carry out the peptide cyclization reaction. The reaction was stopped by adding acetic acid to the reaction solution, and the reaction solution was concentrated under reduced pressure using Genevac EZ-II elite. The obtained crude product was purified under the following conditions (column: Waters XBridge® C18 5 μm 30 x 150 mm; mobile phase: A = 0.1% TFA (in water), B = 0.1% TFA (in MeCN); temperature: 40°C; gradient (%B): 8.0-33.0% over 3.0 minutes, 33.0-38.0% over 8 minutes, 38.0-60.0% over 1 minute; flow rate: 45 mL / min). The portion containing the target substance was collected and freeze-dried to obtain the target peptide. The purity of the target substance was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analytical conditions. The purity of the target substance was 95.9%. Analysis conditions A: Retention time = 4.45 minutes, ESI-MS (+), Observed value m / z = 890.14 (M+3H) ３＋ 【0171】 Example 1-13 Synthesis of Structure No. 114. 【0172】 【0173】The target peptide was synthesized using Sieber amide resin (Watanabe Chemical, 0.6 mmol / g, 0.17 g). A CEM Liberty Blue was used as the solid-phase synthesizer, and the synthesis was carried out according to the manufacturer's manual. To remove Fmoc from the solid-phase resin, 10% pyrrolidine (in DMF) was used, and the reaction was carried out once for 1 minute at 90°C. To introduce each residue, 0.21 M Fmoc-AA (in DMF) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (5.25 equivalents / 10 equivalents / 5 equivalents) were used per equivalent of resin, and the reaction was carried out once for 10 minutes at 90°C. For the third residue, a reaction was carried out once at 90°C for 3 minutes using 0.21 M Fmoc-AA (in NMP) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (5.25 equivalents / 10 equivalents / 5 equivalents). For the fourth, seventh, and ninth residues, a reaction was carried out once at 90°C for 10 minutes using 0.21 M Fmoc-AA (in NMP) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (5.25 equivalents / 10 equivalents / 5 equivalents). For the 5th residue, 0.21 M Fmoc-AA (in NMP) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (5.25 equivalents / 10 equivalents / 5 equivalents) was used, and the reaction was carried out twice at 90°C for 10 minutes each time. For the 8th and 10th residues, 0.21 M Fmoc-AA (in DMF) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (5.25 equivalents / 10 equivalents / 5 equivalents) was used, and the reaction was carried out twice at 90°C for 10 minutes each time. For the 12th residue, a reaction was carried out once at 90°C for 3 minutes using 0.21 M Fmoc-AA (in DMF) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (5.25 equivalents / 10 equivalents / 5 equivalents). For the 13th residue, a reaction was carried out once at 50°C for 15 minutes using 0.21 M Fmoc-AA (in DMF) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (5.25 equivalents / 10 equivalents / 5 equivalents). For the 1st residue, an amino acid with an Alloc main chain and an Fmoc side chain protected was used as the starting material.After introducing each residue, to remove the Fmoc group, the solid-phase resin holding the Fmoc-protected peptide was reacted once with 10% pyrrolidine (in DMF) at 50°C for 1.5 minutes. For residues 5, 8, and 10, the reaction was carried out twice at room temperature for 1 minute each. For residue 13, 4% pyrrolidine + 83 mM / Oxyma pure (in DMF) was reacted once at 90°C for 1 minute. To the solid-phase resin holding the alloc-protected peptide obtained in the previous step, 0.21 M Boc-PEG12c-OH (in DMF) / 0.5 M PyAOP (in DMF) / 1.0 M DIPEA (in DMF) (5 equivalents / 5 equivalents / 10 equivalents) was added and reacted at room temperature for 1 hour. To remove the Alloc group, tetrakis(triphenylphosphine)palladium (0) / phenylsilane (0.2 equivalents / 10 equivalents) and DCM (5 mL) were added to the solid-phase resin and reacted at room temperature for 120 minutes. The resin was washed with DCM and DMF. Chloroacetyl groups were introduced into the solid-phase resin, which retained the peptide obtained in the previous step, by shaking with 0.2 M ClAcNHS (10 equivalents in DMF) at room temperature for 60 minutes. To deprotect the side chains and cleave them from the solid-phase resin, the resin obtained after the chloroacetyl group introduction step was first washed once with DMF, DCM, and diethyl ether, and then dried under reduced pressure. Subsequently, a reaction cocktail (4 mL, TFA / H) was added to the reaction vessel. ２A mixture of O / TIS / DODT in a volume ratio of 92.5 / 2.5 / 2.5 / 2.5 was added and shaken at room temperature for 30 minutes. The reaction mixture was filtered and recovered through the frit. The solid resin remaining in the reaction vessel was shaken again with the cutting cocktail, the solution components were recovered through the frit and mixed with the aforementioned filtrate. When this filtrate was added to 40 mL of a mixed solvent of diisopropyl ether / hexane (1 / 1), a precipitate formed. This mixture was centrifuged and the solution was decanted. The obtained solid was washed again with diethyl ether and dried under reduced pressure. The obtained solid (peptide) was then used in the following cyclization reaction. The peptide was dissolved in DMSO / water / acetonitrile (2 / 1 / 1) to a final concentration of 4 mM based on the number of moles of solid resin, and then 10 equivalents of triethylamine were added and the mixture was stirred at room temperature for 1 hour to carry out the peptide cyclization reaction. The reaction was stopped by adding acetic acid to the reaction solution, and the reaction solution was concentrated under reduced pressure using Genevac EZ-II elite. The peptide was again dissolved in DMSO to a final concentration of 2 mM based on the number of moles of the solid phase resin, and then 10 equivalents of triethylamine were added, and the reaction was carried out by stirring at room temperature for 1 hour to cyclize the peptide. The reaction was stopped by adding acetic acid to the reaction solution, and the reaction solution was concentrated under reduced pressure using Genevac HT-12. The obtained solid (peptide) was dissolved in DMSO to a final concentration of 20 mM based on the number of moles of the solid phase resin, and Biotin-OSu (1.1 equivalents, CAS: 35012-72-0) and DIPEA (1.5 equivalents) were added, and the mixture was stirred at room temperature for 2 hours. The reaction was stopped by adding acetic acid to the reaction solution. The obtained crude product was purified using the following conditions (column: Waters XBridge® C18 5 μm 50 x 150 mm; mobile phase: A = 0.1% TFA (in water), B = 0.1% TFA (in MeCN); temperature: 40°C; gradient (%B): 5.0–5.0% over 2 minutes, 5.0–29.0% over 1 minute, 29.0–34.0% over 8 minutes, 34.0–60.0% over 1 minute; flow rate: 20–20 mL / min over 1 minute, 20–120 mL / min over 1 minute, then 120 mL / min). The portion containing the target substance was collected and freeze-dried to obtain the target peptide.The purity of the target substance was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analysis conditions. The purity of the target substance was 89.8%. Analysis condition A: Retention time = 4.02 mins, ESI-MS (+), Observed value m / z = 878.43 (M + 3H). ３＋ 【0174】 Example 1-14 Synthesis of Structure No. 154. 【0175】 【0176】The target peptide was synthesized using H-Gly-Barlos resin (Watanabe Chemical, 0.86 mmol / g, 0.29 g). A CEM Liberty Blue HT was used as the solid-phase synthesizer, and the synthesis was carried out according to the manufacturer's manual. To remove Fmoc from the solid-phase resin, 10% pyrrolidine (in DMF) was used, and the reaction was carried out twice for 1 minute at room temperature. To introduce each residue, 0.21 M Fmoc-AA (in DMF) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (4.2 equivalents / 8 equivalents / 4 equivalents) were used per equivalent of resin, and the reaction was carried out once for 15 minutes at 50°C. However, residues 5, 8, 10, and 11 were reacted twice for 15 minutes at 50°C. For residues 3 and 7, 0.21 M Fmoc-AA (in NMP) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (4.2 equivalents / 8 equivalents / 4 equivalents) was used, and the reaction was carried out once at 50°C for 15 minutes. For residue 1, Alloc-dk(Fmoc)-OH was used. For the modification of the side chain of residue 1, 0.21 M Boc-PEG12c-OH (in DMF) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (4.2 equivalents / 8 equivalents / 4 equivalents) was used, and the reaction was carried out once at 50°C for 15 minutes. To remove the Fmoc group after the introduction of each residue, the solid-phase resin containing the Fmoc-protected peptide was reacted twice at room temperature for 1 minute each time with 10% pyrrolidine (in DMF). To remove the Alloc group from the main chain, tetrakis(triphenylphosphine)palladium (0) / phenylsilane (0.2 equivalents / 20 equivalents) and DCM (5 mL) were added to the solid-phase resin and reacted at room temperature for 60 minutes. The resin was washed with DCM and DMF. The solid-phase resin (0.083 mmol) containing the peptide obtained in the previous step was reacted once at 40°C for 30 minutes with 0.21 M Fmoc-Meds(tBu)-OH (in DMF) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (3.2 equivalents / 9 equivalents / 4.5 equivalents). The Fmoc group of the α-amino group was removed by reacting it twice for 1 minute each time at room temperature using 10% pyrrolidine (in DMF).To cleave from the solid phase resin, a reaction cocktail (3 mL, a mixture of HFIP / DCM in a volume ratio of 1 / 4) was added to the reaction vessel and shaken at room temperature for 60 minutes. After filtering and recovering the reaction solution through the frit, the reaction solution was concentrated under reduced pressure using Genevac EZ-II elite. The residue was washed with diisopropyl ether (40 mL), and the mixture was centrifuged to decantate the solution. The resulting solid was washed again with diisopropyl ether and dried under reduced pressure. The resulting solid (peptide) was then used in the following cyclization reaction. The peptide was dissolved in DMF to a final concentration of 1.7 mM based on the number of moles of the solid phase resin, and then HATU / DIPEA (1.1 equivalents / 5 equivalents) was added, and the peptide was cyclized by stirring at room temperature for 60 minutes. The reaction was stopped by adding acetic acid to the reaction solution, and the reaction solution was concentrated under reduced pressure using Genevac HT-12. To deprotect the side chains, add the reagent cocktail (3 mL, TFA / H) to the reaction vessel. ２ A mixture of O / TIS / DODT in a volume ratio of 92.5 / 2.5 / 2.5 / 2.5 was added and shaken at room temperature for 45 minutes. The reaction mixture was filtered and recovered through the frit. The solid resin remaining in the reaction vessel was shaken again with the cutting cocktail, the solution components were recovered through the frit and mixed with the aforementioned filtrate. When this filtrate was added to 40 mL of diethyl ether solvent, a precipitate formed. This mixture was centrifuged and the solution was decanted. The resulting solid was washed again with diethyl ether and dried under reduced pressure. The obtained crude product was purified using the following conditions (column: Waters XSelect® C18 5 μm 30 x 150 mm; mobile phase: A = 0.1% TFA (in water), B = 0.1% TFA (in MeCN); temperature: 50°C; gradient (%B): 5.0-28% over 3 minutes, 28-33% over 2 minutes, 33-60% over 1 minute; flow rate: 45 mL / min). The portion containing the target substance was collected and freeze-dried to obtain the target peptide. The purity of the target substance was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analytical conditions. The purity of the target substance was 95.7%. Analytical condition A: retention time = 3.94 min ESI-MS (+) Observed value m / z = 873.09 (M + 3H) ３＋ 【0177】 Example 1-15 Synthesis of Structure No. 54. 【0178】 【0179】 The target peptide was synthesized using Sieber Amide resin (Watanabe Chemical, 0.57 mmol / g, 0.088 g). A Biotage Syro I was used as the solid-phase synthesizer, and the synthesis was carried out according to the manufacturer's manual. To remove Fmoc from the solid-phase resin, 20% piperidine (in DMF) was used, and the reaction was carried out at room temperature for 5 minutes and then 10 minutes. To introduce each residue, 0.21 M Fmoc-AA (in DMF) / 0.5 M HATU (in DMF) / 1.05 M DIPEA (in DMF) (6.3 equivalents / 6 equivalents / 12.6 equivalents) were used per equivalent of resin, and the reaction was carried out at 75°C for 20 minutes twice. However, the 13th residue was reacted at 40°C for 30 minutes twice. The reactions for residues 1, 2, 8, and 11 were carried out twice at 75°C for 30 minutes each. For residue 7, 0.21 M Fmoc-AA (in NMP) / 0.5 M HATU (in DMF) / 1.05 M DIPEA (in DMF) (6.3 equivalents / 6 equivalents / 12.6 equivalents) were used, and the reactions were carried out twice at 75°C for 30 minutes each. For residues 3, 4, and 9, 0.21 M Fmoc-AA (in NMP) / 0.5 M HATU (in DMF) / 1.05 M DIPEA (in DMF) (6.3 equivalents / 6 equivalents / 12.6 equivalents) were used, and the reactions were carried out twice at 75°C for 20 minutes each. To remove the Fmoc group after the introduction of each residue, the solid-phase resin containing the Fmoc-protected peptide was reacted with 20% piperidine (in DMF) at room temperature for 5 minutes and 10 minutes. Chloroacetyl groups were introduced into the solid-phase resin containing the peptide obtained in the previous step by shaking at room temperature for 5 minutes with ClAcOH (5 equivalents) and HATU / DIPEA (5 equivalents / 5 equivalents, in 1.5 mL of DMF). To deprotect the side chains and cleave them from the solid-phase resin, the resin obtained after the chloroacetyl group introduction step was first washed once with DMF, DCM, and diethyl ether, and then dried under reduced pressure. Subsequently, a reaction cocktail (4 mL, TFA / H) was added to the reaction vessel. ２A mixture of O / TIS / DODT in a volume ratio of 92.5 / 2.5 / 2.5 / 2.5 was added and shaken at room temperature for 30 minutes. The reaction mixture was filtered and recovered through the frit. The solid resin remaining in the reaction vessel was shaken again with the cutting cocktail, the solution components were recovered through the frit and mixed with the aforementioned filtrate. When 35 mL of a mixed solvent of diisopropyl ether / hexane (1 / 1) was added to this filtrate, a precipitate was formed. This mixture was centrifuged and the solution was decanted. The obtained solid was washed again with diethyl ether and dried under reduced pressure. The obtained solid (peptide) was then used in the following cyclization reaction. The peptide was dissolved in DMSO / water (9 / 1) to a final concentration of 2 mM based on the number of moles of solid resin, and then 10 equivalents of triethylamine were added and the mixture was stirred at room temperature for 15 hours to carry out the peptide cyclization reaction. The reaction was stopped by adding acetic acid to the reaction solution, and the reaction solution was concentrated under reduced pressure using Genevac EZ-II elite. To modify the side chain of the obtained cyclic peptide, it was dissolved in DMSO (2 mL) to a concentration of 16.7 mM based on the number of moles of solid resin, and then 5 equivalents of triethylamine and SulfoCy5-NHS (CAS: 1497420-70-8, 1.05 equivalents in 1.0 mL of DMSO) were added. The mixture was stirred at room temperature for 120 minutes, and then the reaction was stopped by adding acetic acid. The obtained crude product was purified using the following conditions (column: Waters XSelect® C18 5μm 19x150mm; mobile phase: A = 0.1% TFA (in water), B = 0.1% TFA (in MeCN); temperature: 60°C; gradient (%B): 9.0-34% over 3 minutes, 34-39% over 8 minutes, 39-60% over 1 minute; flow rate: 17 mL / min). The portion containing the target substance was collected and freeze-dried to obtain the target peptide. The purity of the target substance was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analytical conditions. The purity of the target substance was 88.2%. Analytical condition A: retention time = 5.02 min ESI-MS (+) Observed value m / z = 1012.40 (M + 3H) ３＋ 【0180】 Example 1-16 Synthesis of Structure No. 94. 【0181】 【0182】 The target peptide was synthesized using H-Cys(Trt)-Trt(2-Cl) resin (Watanabe Chemical, 0.63 mmol / g, 0.40 g). A CEM Liberty Blue solid-phase synthesizer was used, and the synthesis was carried out according to the manufacturer's manual. To remove Fmoc from the solid-phase resin, 10% pyrrolidine (in DMF) was used, and the reaction was carried out twice for 1 minute at room temperature. To introduce each residue, 0.21 M Fmoc-AA (in DMF) / 0.5 M HATU (in DMF) / 1.0 M DIPEA (in DMF) (4.2 equivalents / 4 equivalents / 8 equivalents) were used per equivalent of resin, and the reaction was carried out once for 30 minutes at room temperature. However, for residues 5 and 8, the reaction was carried out twice for 30 minutes at room temperature. For the third residue, a reaction was carried out once at room temperature for 30 minutes using 0.21 M Fmoc-AA (in NMP) / 0.5 M HATU (in DMF) / 1.0 M DIPEA (in DMF) (4.2 equivalents / 4 equivalents / 8 equivalents). The solid phase resin containing the Fmoc-protected peptide obtained in the previous step was reacted twice at room temperature for 1 minute each with 10% pyrrolidine (in DMF) to remove the Fmoc group from the α-amino group. Chloroacetyl groups were then introduced by shaking with 0.18 M ClAcNHS (in DMF, 5 equivalents) at room temperature for 60 minutes. To deprotect the side chain and cleave it from the solid phase resin, the resin obtained after the chloroacetyl group introduction step was first washed once with DMF, DCM, and diethyl ether, and then dried under reduced pressure. Subsequently, a reaction cocktail (11 mL, TFA / H) was added to the reaction vessel containing the solid phase resin. ２A mixture of O / TIS / DODT in a volume ratio of 92.5 / 2.5 / 2.5 / 2.5 was added and shaken at room temperature for 30 minutes. The reaction mixture was filtered and recovered through the frit. The solid resin remaining in the reaction vessel was shaken again with the cutting cocktail, the solution components were recovered through the frit and mixed with the aforementioned filtrate. This filtrate was divided into two parts and each was added to 40 mL of a mixed solvent of diisopropyl ether / hexane (1 / 1), resulting in precipitation. This mixture was centrifuged and the solution was decanted. The obtained solid was washed again with diethyl ether and dried under reduced pressure. The obtained solid (peptide) was then used in the following cyclization reaction. The peptide was dissolved in water / MeCN (1 / 1) to a final concentration of 2.5 mM based on the number of moles of solid resin, and then 10 equivalents of triethylamine were added and the mixture was stirred at room temperature for 60 minutes to carry out the peptide cyclization reaction. The reaction was stopped by adding acetic acid to the reaction solution, and the reaction solution was concentrated under reduced pressure using Genevac EZ-II elite. The resulting crude product was purified under the following conditions (column: Waters XBridge® C18 5 μm 50 x 150 mm; mobile phase: A = 0.1% TFA (in water), B = 0.1% TFA (in MeCN); temperature: 40°C; gradient (%B): 5.0–5.0% over 2 minutes, 5.0–29.0% over 1 minute, 29.0–34.0% over 8 minutes, 34.0–60.0% over 1 minute; flow rate: 20–20 mL / min over 1 minute, 20–120 mL / min over 1 minute, then 120 mL / min). The portion containing the target substance was collected and freeze-dried to obtain a cyclic peptide. The obtained cyclic peptide was used as a starting material and subjected to the same reaction and purification conditions as in Examples 1-3 to obtain the target peptide. The purity of the target product was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analytical conditions. The purity of the target product was 95.8%. Analytical condition A: Retention time = 4.23 mins ESI-MS (+) Observed value m / z = 1187.13 (M + 2H) ２＋ 【0183】 Example 1-17 Synthesis of Structure No. 149. 【0184】 【0185】The target peptide was synthesized using H-Ala-Barlos resin (Watanabe Chemical, 1.08 mmol / g, 0.23 g) under the same reaction and purification conditions as in Examples 1-13. A CEM Liberty Blue HT was used as the solid-phase synthesizer, and the synthesis was carried out according to the manufacturer's manual. The purity of the target product was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analytical conditions. The purity of the target product was 97.6%. Analytical conditions A: Retention time = 4.00 min, ESI-MS (+), Observed value m / z = 863.10 (M + 3H) ３＋ 【0186】 Example 1-18 Synthesis of Structure No. 218. 【0187】 【0188】 To one equivalent of Cl-Trt(2-Cl) resin (Watanabe Chemical, 1.18 mmol / g, 0.26 g), a solution of Fmoc-dk(Alloc)-OH / DIPEA (1 equivalent / 3 equivalents) dissolved in DCM / DMF (10 mL, 1 / 3) was added and the mixture was stirred at room temperature for one hour. The resin was washed with DMF, DCM, and diethyl ether and dried. To remove the Alloc group from the side chain, tetrakis(triphenylphosphine)palladium(0) / phenylsilane (0.2 equivalents / 10 equivalents) and DCM (10 mL) were added to the solid phase resin and reacted at room temperature for 60 minutes. The resin was washed with DCM and DMF. To the obtained resin, Biotin-PEG12c-OH / HATU / DIPEA (3.2 equivalents, CAS: 1621423-14-0 / 3 equivalents / 6 equivalents, in 10 mL of DMF) was added and the mixture was stirred at room temperature for 60 minutes. The target peptide was synthesized using the obtained resin under the same reaction and purification conditions as in Examples 1-14. A CEM Liberty Blue was used as the solid-phase synthesizer, and the synthesis was carried out according to the manufacturer's manual. The purity of the target product was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analytical conditions. The purity of the target product was 93.0%. Analytical condition B: Retention time = 5.66 mins. ESI-MS (+) Observed value m / z = 956.41 (M + 3H) ３＋ 【0189】 Example 1-19 Synthesis of Structure No. 133. 【0190】 【0191】The target peptide, Fmoc-Cys(Trt)-Sieber amide resin (Peptister, 0.42 mmol / g, 0.15 g), was synthesized. A CEM Liberty Blue solid-phase synthesizer was used, and the synthesis was carried out according to the manufacturer's manual. To remove Fmoc from the solid-phase resin, 10% pyrrolidine (in DMF) was used, and the reaction was carried out once for 1 minute at 90°C. To introduce each residue, 0.21 M Fmoc-AA (in DMF) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (4.2 equivalents / 12 equivalents / 6 equivalents) were used per equivalent of resin, and the reaction was carried out once for 3 minutes at 90°C. For residues 3 and 7, a reaction was carried out once at 90°C for 3 minutes using 0.21 M Fmoc-AA (in NMP) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (4.2 equivalents / 12 equivalents / 6 equivalents). For residues 5 and 8, a reaction was carried out twice at 90°C for 10 minutes using 0.21 M Fmoc-AA (in DMF) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (4.2 equivalents / 12 equivalents / 6 equivalents). For the 10th residue, a reaction was carried out once at 90°C for 10 minutes using 0.21 M Fmoc-AA (in DMF) / 1.0 M DIC (in DMF) / 0.5 M Oxyma pure (in DMF) (4.2 equivalents / 12 equivalents / 6 equivalents). For the 1st residue, an amino acid with an Alloc side chain and an Fmoc main chain was used as the starting material. After introducing each residue, to remove the Fmoc group, a reaction was carried out once at 50°C for 1.5 minutes using 10% pyrrolidine (in DMF) on a solid resin holding the Fmoc-protected peptide. For the 5th, 8th, and 10th residues, the reaction was carried out twice at room temperature for 1 minute each. To remove the Alloc group, tetrakis(triphenylphosphine)palladium (0) / phenylsilane (0.2 equivalents / 10 equivalents) and DCM (5 mL) were added to the solid-phase resin and reacted at room temperature for 60 minutes. The resin was washed with DCM and DMF. To the solid-phase resin retaining the peptide obtained in the previous step, Biotin-PEG12c-OH / PyAOP / DIPEA (in 3 mL of DMF) (10 equivalents / 10 equivalents / 10 equivalents) was added and reacted at room temperature for 1 hour.To remove Fmoc from the solid phase resin, 10% pyrrolidine (in DMF) was used, and the reaction was carried out twice at room temperature for 5 minutes. Chloroacetyl groups were introduced into the solid phase resin, which retained the peptide obtained in the previous step, by shaking with 0.10 M ClAcNHS (5 equivalents in DMF) at room temperature for 60 minutes. To deprotect the side chains and cleave them from the solid phase resin, the resin obtained after the chloroacetyl group introduction step was first washed once with DMF, DCM, and diethyl ether, and then dried under reduced pressure. Subsequently, a reaction cocktail (3 mL, TFA / H) was added to the reaction vessel containing the solid phase resin. ２A mixture of O / TIS / DODT in a volume ratio of 90.0 / 2.5 / 2.5 / 5.0 was added and shaken at room temperature for 90 minutes. The reaction mixture was filtered and recovered from the frit. The solid resin remaining in the reaction vessel was shaken again with the cutting cocktail, the solution components were recovered from the frit and mixed with the aforementioned filtrate. When 40 mL of a mixed solvent of diisopropyl ether / hexane (1 / 1) was added to this filtrate, a precipitate was formed. This mixture was centrifuged and the solution was decanted. The obtained solid was washed again with diethyl ether and dried under reduced pressure. The obtained solid (peptide) was then used in the following cyclization reaction. The peptide was dissolved in water / MeCN (1 / 1) to a final concentration of 2.5 mM based on the number of moles of solid resin, and then 10 equivalents of triethylamine were added and the peptide was cyclized by stirring at room temperature for 360 minutes. The reaction was stopped by adding acetic acid to the reaction solution, and the reaction solution was concentrated under reduced pressure using Genevac EZ-II elite. The resulting crude product was purified under the following conditions (column: Waters XBridge® C18 5 μm 30 x 150 mm; mobile phase: A = 0.1% TFA (in water), B = 0.1% TFA (in MeCN); temperature: 50°C; gradient (%B): 5.0-29.0% over 3 minutes, 29.0-34.0% over 8 minutes, 34.0-60.0% over 1 minute; flow rate: 45 mL / min). The portion containing the target substance was collected and freeze-dried to obtain the target peptide. The purity of the target substance was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analytical conditions. The purity of the target substance was 94.6%. Analysis conditions A: Retention time = 4.04 minutes, ESI-MS (+), Observed value m / z = 869.00 (M+3H) ３＋ 【0192】 Examples 1-20 Synthesis of Structure No. 224. 【0193】 To a solution of DMF (3.05 mL) / 100 mM NH4OAc aq (1.52 mL), the peptide SEQ ID No. 136 (125 mg) synthesized in Examples 1-5 was dissolved, and then copper(II) chloride dihydrate (11.7 mg, CAS: 10125-13-0) was added at room temperature. The reaction mixture was stirred at room temperature for 180 minutes. Then, the reaction mixture was stirred at 80°C for 60 minutes. The resulting reaction mixture was purified under the following conditions (column: YMC-Actus Triart Prep C18-S 10 μm 20 x 250 mm; mobile phase: A = 0.1% TFA (in water), B = 0.1% TFA (in MeCN); temperature: 50°C; gradient (%B): 5.0-29.0% over 5 minutes, 29-34% over 13.2 minutes, 34-60% over 3 minutes; flow rate: 17 mL / min). The portion containing the target substance was collected and freeze-dried to obtain the target peptide. The purity of the target substance was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analytical conditions. The purity of the target substance was 98.3%. Analytical condition B: retention time = 5.42 min ESI-MS (+) Observed value m / z = 743.00 (M + 3H) ３＋ 【0194】 Example 1-21 Synthesis of Structure No. 225. Peptide SEQ ID No. 136 (125 mg) synthesized in Examples 1-5 was dissolved in 100 mM NaOAc aq (4.57 mL), and then lanthanum chloride heptahydrate (255 mg, CAS: 10025-84-0) was added at room temperature. The reaction mixture was stirred at 45°C for 60 minutes and then at 65°C for 60 minutes. The resulting reaction mixture was purified using the following conditions (column: YMC-Actus Triart Prep C18-S 10 μm 20 x 250 mm; mobile phase: A = 0.1% TFA (in water), B = 0.1% TFA (in MeCN); temperature: 50°C; gradient (%B): 5.0-29.0% over 5 minutes, 29-34% over 13.2 minutes, 34-60% over 3 minutes; flow rate: 17 mL / min). The portion containing the target substance was collected and freeze-dried to obtain the target peptide. The purity of the target substance was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analytical conditions. The purity of the target substance was 97.2%. Analytical condition B: retention time = 5.42 min ESI-MS (+) Observed value m / z = 767.76 (M + 3H) ３＋ 【0195】 Example 1-22 Synthesis of Structure No. 226. To 0.55 mL of DMF and 2.19 mL of 100 mM NaOAc aq, 75 mg of peptide SEQ ID No. 136 synthesized in Examples 1-5 was dissolved, and then 19.3 mg of gallium(III) chloride (CAS: 13450-90-3) was added at room temperature. The reaction mixture was stirred at room temperature for 180 minutes and then at 80°C for 60 minutes. The resulting reaction mixture was purified using the following conditions (column: YMC-Actus Triart Prep C18-S 10 μm 20 x 250 mm; mobile phase: A = 0.1% TFA (in water), B = 0.1% TFA (in MeCN); temperature: 50°C; gradient (%B): 5.0–28.0% over 5 minutes, 28–33% over 13.2 minutes, 33–60% over 3 minutes; flow rate: 17 mL / min). The portion containing the target substance was collected and freeze-dried to obtain the target peptide. The purity of the target substance was calculated from the area ratio of the LC / MS (UV wavelength 225 nm) chromatogram under the analytical conditions. The purity of the target substance was 97.1%. Analytical condition B: Retention time = 5.03 min ESI-MS (+) Observed value m / z = 744.73 (M + 3H) ３＋ 【0196】Example 2 Synthesis of various peptides and conjugates In this example, the peptides and conjugates shown in Table 7 were synthesized in the same manner as in Example 1. Structure Nos. 1-35, 37-39, and 180-181 were synthesized in the same manner as in Example 1-1. Structure No. 135 was synthesized in the same manner as in Example 1-2. Structure Nos. 46-51, 55-60, 63-67, 92-93, 95-100, 119, 122-131, 137-138, 155-162, 172-177, 179, 206-211, and 216-217 were synthesized in the same manner as in Example 1-4. Structure No. 36 was synthesized in the same manner as in Example 1-4. Structure No. 136 was synthesized in the same manner as in Example 1-5. Structure No. 40 was synthesized in the same manner as in Example 1-6. Structure No. 170 was synthesized in the same manner as in Example 1-7. Structure No. 41 was synthesized in the same manner as in Example 1-8. Structure No. 171 was synthesized in the same manner as in Example 1-9. Structure Nos. 120-121 were synthesized in the same manner as in Example 1-10. Structure Nos. 134 and 178 were synthesized in the same manner as in Example 1-11. Structure No. Structure Nos. 61-62, 68-91, 139-148, 182-195, 200-202, 205, and 223 were synthesized. Structure Nos. 109-118, 166-169, 196, 199, and 203-204 were synthesized in the same manner as in Example 1-13. Structure Nos. 152-154 were synthesized in the same manner as in Example 1-14. Structure Nos. 42-45 and 52-54 were synthesized in the same manner as in Example 1-15. Structure No. 94 was synthesized in the same manner as in Example 1-16. Structure Nos. 149-151 were synthesized in the same manner as in Example 1-17. Structure Nos. 218-222 were synthesized in the same manner as in Example 1-18. Structure Nos. 101-108, 132-133, 163-165, 197-198, and 212-215 were synthesized in the same manner as in Example 1-19.Table 8 shows the amino acid sequences of the synthesized peptides and the peptides contained in the conjugates. Table 9 shows a correspondence table between the Structure No. in Table 7 and the SEQ ID No. in Table 8. In the cyclization column, "free" means that the peptide is cyclized without a chloroacetyl group. In the table, (amino acid residue) @ and @ (amino acid residue) mean that an amide bond is formed between the carboxyl group of the former and the amino group of the latter, resulting in a cyclic peptide. For example, in the peptide of Sequence ID No. 218, an amide bond is formed between the carboxyl group of asparagine (N) at position 13 and the amino group of methylated glycine (MeG) at position 14, resulting in a cyclic peptide. In this cyclic peptide, the methylated glycine (MeG) at position 14 and the d-isomer of lysine (kd) at position 1 are adjacent within the ring. If there is a discrepancy between the following table and the sequence listing, the following table is correct. 【0197】 【0198】 【0199】 【0200】Example 3: Evaluation of Intermolecular Interactions Between Human Claudin 18.2 and Peptides or Conjugates by Surface Plasmon Resonance (SPR) The intermolecular interactions of the various peptides or conjugates synthesized in Examples 1 and 2 with respect to the human Claudin 18.2 protein were tested using the following method. The specific test method is described below. 【0201】 SPR measurement: A CM3 sensor chip (Cytiva) was inserted into the BiacoreT200 (Cytiva), and the system was primed and equilibrated with running buffer: 1X HBS-P+ (Cytiva), 1.0% DMSO (Fujifilm Wako Pure Chemical Industries, Ltd.), and 0.05% bDDM (DOJINDO). The capture molecule THE ＴＭImmobilization of His Tag Antibody, mAb, Mouse (GenScriptCat. No. A00186) (hereinafter referred to as His antibody) was performed. Capture molecules were immobilized at a flow rate of 10 μL / min. 50 μL each of 60 mM MEDC solution (Cytiva) and 650 mM NHS solution (Cytiva) were mixed and reacted at a flow rate of 10 μL / min for 420 seconds. 150 μL of 30 ug / mL His antibody was prepared by diluting with 10 mM acetic acid solution (pH 5.0) and reacted at a flow rate of 10 μL / min for 420 seconds to immobilize 8000 RU of His antibody onto a CM3 sensor chip. After immobilization, capping was performed by reacting with a 1.0 M ethanolamine aqueous solution (Cytiva) at a flow rate of 10 μL / min for 420 seconds. 100 nM Claudin 18.2 diluted in running buffer was reacted at a flow rate of 10 μL / min for 90 seconds, capturing approximately 1,500 RU or more into the flow cell. The synthesized peptide, prepared to 10 mM in DMSO solution, was diluted with running buffer to a final concentration of 10 μM, and then two-stage diluted peptide solutions of 400-40 nM were prepared. Using the above samples, the peptide kinetics relative to human Claudin 18.2 were obtained by SPR measurement. The kinetics evaluation model was Single Cycle Kinetics, and curve fitting was performed using Biacore T200 Evaluation Software Version 3.0 (Cytiva). The binding of the peptide or conjugate to human Claudin 18.2 was evaluated by performing curve fitting using the least squares method on the obtained sensorgrams and determining the KD value. The results are shown in Table 7. As shown in Table 7, the peptide and conjugate of the present invention were shown to have binding activity to human Claudin 18.2. In Table 7, NT indicates that it was not measured. 【0202】 Example 4: Binding evaluation test between human Claudin 18.2-expressing cells and peptide or conjugate using FACS (fluorescence-activated cell sorting) 1.2 × 10 ５Human colon cancer-derived HT-29 cell line overexpressing human CLDN18.2 (HT-29-hCLDN18.2), human pancreatic cancer-derived BxPC-3 cell line overexpressing human CLDN18.2 (BxPC-3-hCLDN18.2), or human embryonic kidney cell-derived HEK293 cell line overexpressing human CLDN18.2 (HEK293-hCLDN18.2) were treated with the compound at a concentration of 10, 30, 100, or 300 nmol / L at 4°C for 30 or 45 minutes, and the cells were washed with PBS (Thermo Fisher Scientific, 14190250). Cells treated with a peptide or conjugate conjugated with Cy5 or Biotin were further treated with 4 μg / mL of Streptavidin, R-Phycoerythrin Conjugate (Thermo Fisher Scientific, S866) at 4°C for 30 or 45 minutes, and then washed with PBS. The wavelength of APC or PE was measured using CytoFLEX S (BECKMAN COULTER Life Sciences, B75442). The results are shown in Table 7. As shown in Table 7, the peptides and conjugates of the present invention were shown to have binding activity to human Claudin 18.2. NT in Table 7 indicates that it was not measured. 【0203】Reference Example: Chelating Method This reference example shows the synthesis of a chelator. Unless otherwise specified, the following equipment, abbreviations, analytical conditions, etc., were used in the reference example. Unless otherwise specified, the proton nuclear magnetic resonance (1H-NMR) of the following synthesis examples was measured in deuterated chloroform or deuterated dimethyl sulfoxide solvent using a JEOL JNM-ECP300, JEOL JNM-ECX300, or Bruker Ascend™500, and the chemical shift is shown as the δ value (ppm) with tetramethylsilane as the internal standard (0.0 ppm). In the description of NMR spectra, "s" means singlet, "d" means doublet, "t" means triplet, "q" means quartet, "dd" means doublet of doublets, "dt" means doublet of triplets, "m" means multiplet, "br" means broad, "J" means coupling constant, "Hz" means Hertz, "CDCl3" means deuterated chloroform, and "DMSO-d6" means deuterated dimethyl sulfoxide. Unless otherwise specified, high-performance liquid chromatography / mass spectrometry was performed using either a Waters ACQUITY UPLC H-Class / QDa, Waters ACQUITY UPLC H-Class / SQD2, or a Shimadzu LC-20AD / Triple Tof5600. In high-performance liquid chromatography / mass spectrometry descriptions, ESI+ is the positive mode of electrospray ionization, and (M+H)+ represents a protonated ion. In high-performance liquid chromatography / mass spectrometry descriptions, ESI- is the negative mode of electrospray ionization, and M-H represents an ion formed by proton desorption. Analytical conditions C Column: ACQUITY® 1.7 μm BEH C18, 2.1 x 100 mm, Waters Mobile phase A: 0.025% TFA Water mobile phase B: 0.025% TFA CH ３ CN column temperature: 60°C. Gradient (%B): 5-95% over 5.56 minutes, then 95% from 5.56 minutes to 7.22 minutes. Flow rate: 0.6 mL / min. Detection: UV 254 nm. 【0204】 Example 1: ddotaga(Mpe)４ Synthesis of -OH 【0205】To 200 mL of dichloromethane (CAS: 75-09-2), (2S)-5-oxooxolane-2-carboxylic acid (20.00 g, CAS: 21461-84-7) and DMF (0.11 g, CAS: 68-12-2) were added at room temperature. Oxalyl chloride (48.78 g, CAS: 79-37-8) was added dropwise to the above mixture over 10 minutes at 0°C. The resulting mixture was stirred at room temperature for a further 2 hours. The reaction mixture was concentrated under reduced pressure. To 184 mL of dichloromethane, 2,6-lutidine (15.93 g, CAS: 108-48-5) and 3-methyl-3-pentanol (25.31 g, CAS: 77-74-7) were added at room temperature. To the above mixture, the product obtained in the previous reaction (18.4 g) was added dropwise over 10 minutes under ice cooling. The resulting mixture was stirred overnight at room temperature. The reaction was quenched by adding water under ice cooling. The organic phase was washed twice with 10% citric acid (CAS: 77-92-9) aqueous solution, twice with saturated sodium bicarbonate (CAS: 144-55-8) aqueous solution, and twice with saturated brine, and then dried over sodium sulfate (CAS: 7757-82-6). After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1), and the fraction containing the target product was concentrated under reduced pressure. The product obtained from the above reaction (15.2 g) was dissolved in isopropanol (450 mL, CAS: 67-63-0), and water (100 mL) and calcium chloride (126 g, CAS: 10043-52-4) were added under ice cooling. To the above mixture, lithium hydroxide (6.80 g, CAS: 1310-65-2) dissolved in water (50 mL) was added under ice cooling. The resulting mixture was stirred further overnight at room temperature. The mixture was adjusted to pH 5 using 1 Maq. HCl (CAS: 7647-01-0). The resulting mixture was filtered, and the filtrate was washed with ethyl acetate. The filtrate was extracted three times with ethyl acetate, the combined organic layers were washed twice with saline solution, and dried over sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The obtained product (14 g) was dissolved in DMF (140 mL), and sodium carbonate (6.35 g, CAS: 497-19-8) was added at room temperature. Benzyl bromide (10.25 g, CAS: 100-39-0) was added dropwise to the above mixture under ice cooling. The resulting mixture was stirred further overnight at room temperature.The reaction was quenched by adding water under ice cooling. The resulting mixture was extracted three times with ethyl acetate. The combined organic layers were washed three times with saline solution and dried over sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20 / 1), and the fraction containing the target product was concentrated under reduced pressure. The resulting product (18.8 g) was dissolved in dichloromethane (200 mL), and triethylamine (7.08 g, CAS: 121-44-8) was added at room temperature. Methanesulfonyl chloride (7.34 g, CAS: 124-63-0) was added dropwise to the above mixture over 10 minutes under ice cooling. The resulting mixture was stirred for a further 1 hour at room temperature, and then the mixture was quenched with water. The resulting mixture was extracted three times with dichloromethane. The organic layers were washed three times with saline solution and dried over sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. At room temperature, 17.29 g of cyclone (CAS: 294-90-6), 200 mL of acetonitrile (CAS: 75-05-8), and 6.94 g of potassium carbonate (CAS: 584-08-7) were added. To the above mixture, a solution of the product obtained in the previous reaction (20.1 g) in acetonitrile (200 mL) was added dropwise at 50°C for 10 minutes. The resulting mixture was stirred at 50°C overnight. After cooling the mixture to room temperature, the resulting mixture was filtered, and the insoluble matter was washed three times with ethyl acetate. The filtrate was washed twice with saline solution and dried over sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The resulting product (19.2 g) was dissolved in acetonitrile (300 mL), and potassium carbonate (50.10 g) was added. To the above mixture, 1-ethyl-1-methylpropyl 2-bromoacetate (29.66 g, CAS: 381212-04-0) was added dropwise over 10 minutes at room temperature. The resulting mixture was stirred overnight at room temperature. The resulting mixture was filtered, insoluble matter was washed twice with acetonitrile, and the filtrate was concentrated under reduced pressure. Subsequently, the resulting mixture was dissolved in ethyl acetate (300 mL), the solution was washed with water (300 mL), saturated sodium bicarbonate aqueous solution (300 mL), and saline solution (300 mL), and dried over sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure.The residue was purified by silica gel column chromatography (dichloromethane / methanol = 20 / 1), and the fraction containing the target product was concentrated under reduced pressure. The obtained product was dissolved in methanol (200 mL), and Pd / C (10%, 2 g) was added under a nitrogen atmosphere. The mixture was stirred overnight at room temperature under a hydrogen atmosphere. The obtained mixture was filtered, and the insoluble matter was washed three times with methanol. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane / methanol = 20 / 1) to obtain the title compound. 1H NMR (500 MHz, DMSO-d6) δ 12.14 (s, 1H), 3.50 - 3.35 (m, 4H), 3.20 - 2.90 (m, 5H), 2.88 - 2.72 (m, 3H), 2.49 - 2.32 (m, 5H), 2.23 - 2.05 (m, 4H), 2.04 - 1.95 (m, 3H), 1.92 - 1.75 (m, 13H), 1.73 - 1.53 (m, 6H), 1.45 - 1.27 (m, 12H), 0.89 - 0.75 (m, 24H). Analytical condition C: retention time = 4.51 min; ESI-MS (+) observed value m / z = 814 (M + H). ＋ , theoretical value m / z = 813. 【0206】 Example 5 １７７ In vivo distribution of Lu-labeled peptide conjugate To the peptide conjugate １７７ Lu-labeled 【0207】 The labeling reaction solution (Table 10) containing the peptide conjugates of Structural Numbers 135, 136, 170, and 171 was heated at 95°C for 10 minutes for labeling. The peptide conjugate chelated with the radioisotope is also referred to as Structural Number 227 (the compound in which Lu is chelated to Structural Number 135), Structural Number 228 (the compound in which Lu is chelated to Structural Number 136), Structural Number 229 (the compound in which Lu is chelated to Structural Number 170), and Structural Number 230 (the compound in which Lu is chelated to Structural Number 171). １７７ Lu-chelated compound), Structural Number 228 (the compound in which Lu is chelated to Structural Number 136) １７７ Lu-chelated compound), Structural Number 229 (the compound in which Lu is chelated to Structural Number 170) １７７ Lu-chelated compound), Structural Number 230 (the compound in which Lu is chelated to Structural Number 171) １７７ Lu-chelated compound). 【0208】 【0209】Radio-HPLC: After mixing the test substance with acetonitrile, the radiochemical purity before and after administration was measured using TSK gel ODS-80Ts QA, 4.6 mm ID × 250 mm, 5 μm (Tosoh). As a result, the purity was 100% before administration and 100% after administration. 【0210】 Radio-TLC: TLC silica gel 60 RP-18 F ２５４ s (Merck, 115389) was developed with a 2 mol / L ammonium acetate solution / acetone mixture (1:1), and the radioactivity before and after administration was measured with a radiochromatizer (energy range 60 - 250 keV, collimator 1.0 cm, V-shaped BGO crystal, measurement time 10 minutes). As a result, the purity was 97.51 - 98.44% before administration and 97.66 - 97.82% after administration. 【0211】 Preparation of evaluation animals (HT-29-hCLDN18.2 tumor-bearing mice): Five-week-old female BALB / cSlc-nu / nu mice were purchased from Japan SLC (Shizuoka, Japan) and used for the preparation of evaluation animals. After acclimation, a 1:2 mixture of PBS pH 7.4 (1×) (Thermo Fisher Scientific, 10010-023) and VitroGel (The Well Bioscience, VHM01) was suspended with 5 × 10 ７ cells / mL of human HT-29 cell line overexpressing human CLDN18.2 (HT-29-hCLDN18.2), and 0.1 mL was transplanted subcutaneously into the right chest of nude mice (6 weeks old) with a disposable syringe with a needle. For evaluation animals, 3 animals per group were used, and a total of 12 groups were used. The evaluation animals at the time of use had a body weight of 16.36 g to 21.14 g and a tumor diameter of 95 to 553 mm ３ at that time. 【0212】 Biodistribution Each compound was administered once intravenously to HT-29-hCLDN18.2 tumor-bearing mice. Anatomies were performed 1, 4, and 24 hours after administration, and the radioactivity concentration (%ID / g) of each tissue was measured. 【0213】 Results １７７ The results of the biodistribution of the Lu-labeled compound are shown in Figures 1, 2, 3, and 4. 【0214】 Example 6 ６４ In vivo distribution of Cu-labeled peptide conjugates to peptide conjugates ６４ Labeling was performed by heating a labeling reaction solution (Table 11) containing Cu-labeled peptide conjugates with structural numbers 135, 136, 170, and 171 at 95°C for 10 minutes. The radioactive isotope-chelated peptide conjugate was labeled with structural number 231 (with structural number 135). ６４ A compound in which Cu is chelated), structural number 232 (same as structural number 136) ６４ Cu chelated compound), structural number 233 (structural number 170) ６４ Cu chelated compound), structural number 234 (structural number 171) ６４ It is also called a chelated compound of Cu. 【0215】 Radio-HPLC: After mixing the test substance with acetonitrile, the radiochemical purity before and after administration was measured using TSK gel ODS-80Ts QA, 4.6 mm ID × 250 mm, 5 μm (Tosoh). The results showed 100% purity before and after administration. Radio-TLC: The test substance was spotted on TLC silica gel 60 RP-18 F. ２５４ After developing s (Merck, 115389) in a 2 mol / L ammonium acetate / acetone mixture (1:1), the radioactivity before and after administration was measured using a radiochromatograph (energy range 60-250 keV, collimator 1.0 cm, V-shaped BGO crystal, measurement time 10 minutes). As a result, the purity was 98.28-98.61% before administration and 98.20-98.63% after administration. 【0216】 Preparation of evaluation animals (HT-29-hCLDN18.2 tumor-bearing mice): Five-week-old female BALB / cSlc-nu / nu mice were purchased from Nippon SLC (Shizuoka, Japan) and used to prepare evaluation animals. After acclimatization, 5 × 10⁻¹⁰⁶ mice were treated with a 1:2 mixture of PBS pH 7.4 (1×) (Thermo Fisher Scientific, 10010-023) and VitroGel (The Well Bioscience, VHM01). ７Human colon cancer-derived HT-29 cell line (HT-29-hCLDN18.2) overexpressing human CLDN18.2 at cells / mL was suspended, and 0.1 mL was transplanted subcutaneously into the right thorax of nude mice (6 weeks old) using a disposable syringe with a needle. Four evaluation groups were used, with three animals per group. At the time of use, the evaluation animals weighed 17.26–19.66 g and had tumor diameters of 250–422 mm. ３ That was the case. 【0217】 PET / CT imaging ６４ PET / CT images were collected under isoflurane anesthesia at 2, 4, 24, and 47.5 hours after administration of Cu-labeled compounds (4.30–4.68 MBq / head). Figure 5 shows the results. Accumulation in the tumor was confirmed for each compound. 【0218】 Example 7 １７７ Efficacy study of Lu-labeled peptide conjugates １７７ Labeling was performed by heating a labeling reaction solution (Tables 12 and 13) containing Lu-labeled peptide conjugates with structural numbers 135, 136, 170, and 171 at 95°C for 10 minutes. The radioactive isotope-chelated peptide conjugate was labeled with structural number 227 (with structural number 135). １７７ Lu chelated compound), structural number 228 (structural number 136) １７７ Lu chelated compound), structural number 229 (structural number 170) １７７ Lu chelated compound), structural number 230 (structural number 171) １７７ It is also called a chelated compound of Lu. 【0219】 Radio-HPLC was used to measure the radiochemical purity of the test substance before administration using a TSK gel ODS-80Ts QA, 4.6 mm ID × 250 mm, 5 μm (Tosoh). The purity results are shown in Table 14. 【0220】 【0221】Radio-TLC testing was performed by spotting the test substance onto TLC silica gel 60 RP-18 F254s (Merck, 115389) and developing it with a 2 mol / L ammonium acetate solution / acetone mixture (1:1). Radioactivity before and after administration was measured using a radiochromatograph (energy range 60-250 keV, collimator 1.0 cm, V-shaped BGO crystal, measurement time 10 minutes). The purity results are shown in Table 15. 【0222】 【0223】 Preparation of evaluation animals: Five-week-old female BALB / cAJcl-nu / nu mice were purchased from CREA Nippon (Tokyo, Japan) and used to prepare evaluation animals. After acclimatization, they were subjected to PBS pH 7.4 (1x) (Thermo Fisher Scientific, 10010-023) for 5x10⁻¹⁰⁻¹ ７ Human pancreatic cancer-derived BxPC3 cell line (BxPC-3-hCLDN18.2) overexpressing human CLDN18.2 at cells / mL was suspended, and 0.1 mL was transplanted subcutaneously into the right thorax of nude mice (6 weeks old) using a disposable syringe with a needle. Ten groups of animals were used for evaluation, with six animals per group. １７７ The animals evaluated the day before administration of the lu-labeled peptide conjugate had a body weight of 23.50 g to 29.85 g and a tumor diameter of 65 to 164 mm. ３ That was the case. 【0224】 Medicinal efficacy evaluation of raw food and １７７ Lu-labeled peptide conjugates (structure numbers 135, 136, 170, and 171) were administered intravenously to tumor-bearing mice at a dose of 30 MBq / head, either as a single dose or at weekly intervals for three doses, 22 days after transplantation of BxPC3-CLDN18.2 cells (Day 0). Body weight and tumor volume were measured twice a week until Day 48, and all surviving mice were euthanized on Day 51. In addition, gemcitabine 100 mg / kg, a chemotherapeutic agent, was administered intraperitoneally once a week for six doses as a reference substance, and tumor diameter and body weight were measured in the same manner. 【0225】 The tumor volume trends for each group are shown in Figure 6. １７７All of the lu-labeled peptide conjugates showed antitumor effects, and the effect was enhanced with increasing administration frequency. On the other hand, gemcitabine did not show any antitumor effect. 【0226】 Figure 7 shows the changes in the weight change rate for each group. １７７ No significant weight loss was observed with the administration of Lu-labeled peptides. 【0227】 Example 8 ２２５ Efficacy testing of Ac-labeled peptide conjugates ２２５ The labeled reaction solution (Table 16) containing the peptide conjugate with Ac-labeled structure number 136 was heated at 95°C for 20 minutes. ２２５ Ac labeling was performed. The peptide conjugate chelated with the radioactive isotope was labeled with structure number 235 (structure number 136). ２２５ It is also called an Ac chelated compound. 【0228】 【0229】 Radio HPLC ２２５ The radiochemical purity of the Ac-labeled peptide conjugate (test substance) was measured before administration using a Mightysil RP-18GP, 4.6 mm x 150 mm, 5 μm filter. The result showed a purity of 99.3%. 【0230】 Radio TLC ２２５ Ac-labeled test material was spotted on an iTLC-SG, developed with a 0.1 mol / L sodium citrate solution, and then cleaved into two parts. Radioactivity was then measured using a gamma counter (Hidex / Hidex Automatic Gamma Counter, detector: NaI crystal). The result showed a purity of over 98.9%. 【0231】 Preparation of evaluation animals: Three-week-old male BALB / c Nude N mice were purchased from Janvier and used to prepare evaluation animals. After acclimatization, they were fed PBS at 5 × 10⁶ times. ７ Human CLDN18.2 overexpressing BxPC-3 cells at cells / mL were suspended, and 0.1 mL was transplanted subcutaneously into the right flank of nude mice (5 weeks old) using a disposable syringe with a needle. Four evaluation groups were used, with 10 animals per group.２２５ Evaluated animals administered with Ac-labeled peptide conjugate had a body weight of 23.5 g to 30.9 g and a tumor diameter of 79 to 297 mm. ３ That was the case. 【0232】 Drug efficacy evaluation ２２５ Ac-labeled peptide conjugates were administered intravenously as a single dose at 30 kBq / head, 60 kBq / head, and 120 kBq / head to human CLDN18.2 overexpressing BxPC-3 tumor-bearing mice 34 days after cell transplantation (Day 0). Body weight and tumor volume were measured twice a week until Day 42, and all surviving mice were euthanized on the final day of measurement. 【0233】 The tumor volume trends for each group are shown in Figure 8. ２２５ The group administered with Ac-labeled peptide conjugate showed a dose-dependent antitumor effect, which was significantly greater than that of the group administered with the base drug. 【0234】 Figure 9 shows the changes in body weight for each group. No significant weight loss was observed in any of the treatments. 【0235】 Based on the above, in the above embodiment... ２２５ Instead of Ac, 213 Bi, 211 At, 227 It is thought that a similar tumor growth inhibitory effect on CLDN18.2-expressing tumors can be obtained even when other alpha-emitting radionuclides such as Th are used. Furthermore, if a beta-emitting radionuclide (for example) is used instead of an alpha-emitting radionuclide 177 Lu, 90 Even when using Y, etc., it is thought that radiotherapy effects based on tumor accumulation by peptides can be obtained. 【0236】 The peptide conjugate according to the present invention has CLDN18.2 binding activity and can be used as a pharmaceutical composition, diagnostic composition, and research composition for the prevention or treatment of CLDN18.2-related diseases.

Claims

1. A conjugate comprising peptide A and a payload, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein peptide A comprises an amino acid sequence represented by formula A1, or an amino acid sequence in which one or more amino acid residues are substituted, deleted, added or inserted in the amino acid sequence represented by formula A1, A1: X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13, where, in peptide A, X1 is any D-amino acid residue, X2 is any amino acid residue, X3 is an amino acid residue having an optionally substituted aryl group in its side chain, X4 is any amino acid residue, X5 is an amino acid residue having an optionally substituted aryl group in its side chain, X6 is an optionally N-alkylated glycine residue (alkyl may have substituents), X7 is any amino acid residue, X8 is N X9 is an N-alkylated glycine residue (the alkyl group may have a substituted or aryl group), X10 is an amino acid residue having an aliphatic hydrocarbon group in its side chain, X11 is a 4-6 membered cyclic secondary amino acid residue, X12 is D, X13 is a peptide (1) C or aMeC, or (2) A or G, further having G, MeG, Medn, Meda, dp, or Meds added to the C-terminus of X13 as the 14th amino acid residue (X14), and the payload is the conjugate, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, comprising a radioisotope and / or a chelating agent.

2. The peptide A is such that in formula A1, X1 is da, dhgl, dp, ds, df4COO, dn, ddab, dk, dyae, dkCopipzaa, dd, dorn, or ddap, X2 is S, 4Py, Cha, Tbg, W7N, F4aao, K, Yae, or IMe, X3 is 3Py6NH2, F4CON, F4OMe, F4Me, or Y, and X4 is Y, F4C, F4F, 3Py6NHaa, Atp, V, Cha, 5Pyrm, F4aao, Tbg, Gthp, Cbg, YaeAc, Yae, or YaeCopipzaa, X5 is 3Py6NH2, Y, or Y3Me, X6 is MeG, HeG, CmG, PeG, AcaeG, CmpG, CmmG, MeopG, or AcapG, X7 is S, 4Py, Nmm, Ndm, HseMe, Hse, 4Pyz1Me, 3Py5CON, 4Py3CON, 3Py6pipz4Ac, K, Yae, YaeCOPipzaa, 3Py6O4thp, F4CON, 3Py6O4pip1Ac, 3Py6CON, 3Py6mor, or 4Pyz, X8 is N, X9 is PeG, mCPeG, or oCPeG, X10 is L or Cba, The conjugate according to claim 1, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein X11 is P or Hpr and X12 is D.

3. The conjugate according to claim 1, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein peptide A comprises an amino acid sequence represented by formula A2, or an amino acid sequence in which 1 to 11 amino acid residues arbitrarily selected from the group consisting of the 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 9th, 10th, 11th, and 13th amino acid residues from the N-terminus of the amino acid sequence represented by formula A2 are substituted or deleted. A2: ddab-Tbg-F4CON-Gthp-Y3Me-HeG-4Py-N-mCPeG-Cba-P-D-C (SEQ ID NO: 136) 4. The conjugate according to any one of claims 1 to 3, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein the peptide A comprises a peptide having the amino acid sequence of SEQ ID NOs: 1 to 179.

5. The conjugate according to any one of claims 1 to 4, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein the peptide A further comprises additional amino acid residues.

6. The conjugate according to any one of claims 1 to 5, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein peptide A is a cyclic peptide.

7. The conjugate according to any one of claims 1 to 6, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein the peptide A is a peptide having a cyclic structure in which the first amino acid residue of the amino acid sequence contained in the peptide A is chloroacetylated, and the chloroacetylated amino acid residue is intramolecularly bonded to C or aMeC contained in the same peptide A.

8. The conjugate according to any one of claims 1 to 6, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein peptide A is a peptide having a cyclic structure in which the amino group of the first amino acid residue of the amino acid sequence contained in peptide A is bonded to the carboxyl group of the C-terminal amino acid residue of peptide A.

9. The conjugate, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof according to any one of claims 1 to 8, wherein (i) the payload is bound to the C-terminus of peptide A with or without a linker, or (ii) the payload is bound to the 1st, 2nd, 4th, or 7th amino acid residue of the amino acid sequence represented by formula A1 of peptide A with or without a linker.

10. The payload comprises the radioactive isotope, a conjugate according to any one of claims 1 to 9, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof.

11. The conjugate according to claim 10, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein the payload comprises the radioisotope bound to the chelating agent.

12. The payload comprises the chelating agent and does not contain the radioisotope, the conjugate according to any one of claims 1 to 9, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof.

13. A pharmaceutical composition comprising the conjugate according to claim 10 or 11, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof.

14. A pharmaceutical composition for preventing or treating Claudin 18.2-related diseases, comprising the conjugate according to claim 10 or 11, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof.

15. A composition for diagnostic or research use comprising the conjugate according to claim 10 or 11, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof.

16. A diagnostic or research composition for diagnosing Claudin 18.2-related diseases, comprising the conjugate according to claim 10 or 11, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof.

17. An imaging agent comprising the conjugate according to claim 10 or 11, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof.

18. An imaging agent for use in tumor diagnosis, comprising the conjugate according to claim 10 or 11, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof.

19. A method for testing a conjugate, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, for testing at least one of the following: a) solubility in a solvent; b) Claudin 18.2 binding activity; c) toxicity to cells and / or tissues; or d) toxicity to experimental animals, wherein the conjugate, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof is a conjugate, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof according to any one of claims 1 to 12.

20. A conjugate comprising peptide B and a payload, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein peptide B comprises an amino acid sequence represented by formula B1, or an amino acid sequence in which one or more amino acid residues are substituted, deleted, added, or inserted in the amino acid sequence represented by formula B1. B1: Y1-Y2-Y3-Y4-Y5-Y6-Y7-Y8-Y9-Y10-Y11-Y12-Y13 where, Y1 is any D-amino acid residue, Y2 is an amino acid residue having an optionally substituted aryl group in its side chain, Y3 is any amino acid residue, Y4 is an amino acid residue having an optionally substituted aryl group in its side chain, Y5 is an optionally N-alkylated glycine residue (the alkyl group may have substituents), Y6 is an amino acid residue having an optionally substituted aryl group in its side chain, Y7 is N, Y8 is an optionally N-alkylated glycine residue (the alkyl group may have an optionally substituted aryl group), Y9 is an amino acid residue having an aliphatic hydrocarbon group in its side chain, Y10 is P, Y11 is D Y12 is an amino acid residue having an optionally substituted aryl group in its side chain, Y13 is a peptide having (1) C or aMeC, or (2) N or bA2SMe, further having MeG or MeS added to the C-terminus of Y13 as the 14th amino acid residue (Y14), and the payload is the conjugate, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, comprising a radioisotope and / or a chelating agent.

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