SSTR receptor targeting radio compounds and uses thereof
A novel compound with a trivalent structure and specific linkers improves SSTR2 binding affinity and tumor uptake, addressing the limitations of current therapies for SSTR2-expressing tumors.
Patent Information
- Application Number
- PCT/CN2024/135619
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-11-08
- Filing Date
- 2024-11-29
- Publication Date
- 2025-06-05
AI Technical Summary
Current approaches for targeting somatostatin receptor 2 (SSTR2) in tumors lack sufficient tumor cell selectivity and therapeutic efficacy.
A compound comprising a trivalent moiety connected to a SSTR2 binding moiety, an effector moiety, and a fatty acid moiety via linkers, enhancing binding affinity and tumor uptake while maintaining fast systemic clearance.
The compound demonstrates higher binding affinity to SSTR2 and increased tumor uptake, potentially achieving better therapeutic outcomes and a larger therapeutic window compared to traditional molecules like DOTATATE.
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Figure PCTCN2024135619-FTAPPB-I100001 
Figure PCTCN2024135619-FTAPPB-I100002 
Figure PCTCN2024135619-FTAPPB-I100003
Abstract
Description
SSTR RECEPTOR TARGETING RADIO COMPOUNDS AND USES THEREOFCROSS-REFERENCEThis application claims the benefit of priority to International Patent Application No. PCT / CN2023 / 135488, filed on November 30, 2023, and to International Patent Application No. PCT / CN2024 / 121427, filed on September 26, 2024, and to International Patent Application No. PCT / CN2024 / 130720, filed on November 08, 2024, the entire contents of each of which are incorporated herein by reference.FIELDThe present application relates generally to the field of compounds that target cell surface receptors such as somatostatin receptors. In particular, it relates to compounds comprising radionuclides. The application also relates to the methods of using the compounds or pharmaceutically acceptable salts thereof for targeting and / or killing tumor cells expressing somatostatin receptor 2 (SSTR2) .BACKGROUNDSomatostatin, also known as growth hormone-inhibiting hormone (GHIH) , is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones. Somatostatin receptor type 2 (SSTR2) can be activated by somatostatin, which in humans is encoded by the SSTR2 gene. SSTR2 is most highly expressed in the pancreas (both alpha-and beta-cells) , but also in other tissues such as the cerebrum and kidney and in lower amount in the jejunum, colon and liver. The abnormality of the SSTR2 signaling pathway has been found to be associated with various diseases including cancers.It has been well studied that the high expression of Somatostatin type 2 receptor (SSTR2) is an important characteristic of neuroendocrine tumors. Consequently, SSTR2 has been explored extensively as a therapeutic target to deliver SSTR2-binding peptide complexed radionuclides to the tumor tissue, which enables PET or SPECT / CT-based diagnosis and internalα orβ-radiation therapy. However, new approaches with higher tumor cell selectivity meanwhile robust efficacy are still in demand. The present application addresses these needs.SUMMARYIn one aspect, provided herein is a compound of formula (I) , or a pharmaceutically acceptable salt thereof:wherein:T is a trivalent moiety,Z is a somatostatin receptor 2 (SSTR2) binding moiety, wherein Z is conjugated to T via a linker LZ,E is an effector moiety, wherein E is conjugated to T via a linker LE,A is an unsubstituted or substituted fatty acid moiety, wherein A is conjugated to T via a linker LA, andLZ, LE, and LA are each independently a bond or a divalent linker.In some embodiments, LA is a bond or a divalent linker: – (Y) n-, wherein: n is an integer of 1-20, and each Y is independently selected from the group consisting of an amino acid residue and -N (RN) (C2alkyleneYa) y1YbC (O) -, wherein RN is H or C1-C6 alkyl, wherein Ya is -O-, -S-, -NH-, or -N (C1-C6 alkyl) -, wherein y1 is an integer from 1 to 10, and wherein Yb is C1-C3 alkylene. In some embodiments, LA comprises one or more amino acid residues. In some embodiments, LA comprises one or more amino acid residues, each independently selected from the group consisting of alanine (Ala, A) , asparagine (Asn, N) , aspartic acid (Asp, D) , glutamine (Gln, Q) , glutamic acid (Glu, E) , γGlu, glutamine (Gln) , glycine (Gly, G) , isoleucine (Ile, I) , leucine (Leu, L) ,εLys, methionine (Met, M) , phenylalanine (Phe, F) , proline (Pro, P) , serine (Ser, S) , threonine (Thr, T) , tryptophan (Trp, W) , tyrosine (Tyr, Y) , valine (Val, V) , pyrrolysine (Pyl, O) , pyrroline-carboxy-lysine (PCL) , gamma-carboxyglutamic acid (Gla) , NR5C5alkyleneC (O) (Ahx) , Cysteic acid (Cya) , norleucine (Nle) , norvaline (Nva) , 2-aminooctanoic acid (Aoc) , 2-naphthylalanine (2-Nal) , 3- (trifluoromethyl) phenylalanine (TFP) , homophenylalanine (hPhe) , cyclohexylalanine (Cha) , 1-naphthylalanine (1-Nal) , 4-benzoyl-L-phenylalanine (Bpa) , 2-methoxy-4-vinylphenylalanine (MvF) , 4-fluorophenylalanine (4-F-Phe) , 4-phenyl-2, 3-dihydroxy-6-nitrophenylalanine (pNIPA) , 2- (2-naphthyl) alanine (2-Nal-ala) , 4- (4-propoxyphenyl) alanine (Ppa) , 4-carboxyphenylalanine (4-CPA) , 4-butylphenylalanine (Bua) , 2-nitrophenylalanine (2-Npa) , 4-azidophenylalanine (4-AzF) , 2- (4-nitrophenyl) ethylalanine (2-Npe) , 3-iodo-L-tyrosine (Ity) , 5, 5, 5-trifluoroleucine (TFL) , or a D enantiomer thereof. In some embodiments, LA comprises one or more negatively charged amino acid residues, wherein each of the negatively charged amino acid residues is independently and optionally selected from the group consisting of D-Asp, Asp, D-Glu, Glu, D-γGlu, γGlu, and Cya. In some embodiments, LA comprises one or more D-Asp, Asp, or any combination thereof. In some embodiments, LA comprises one or more neutral amino acid residues, wherein each amino acid residue is independently and optionally selected from the group consisting of Gly, D-Pro, Pro, D-Ser and Ser. In some embodiments, LA comprises one or more neutral amino acid residues, wherein each amino acid residue is independently and optionally selected from the group consisting of Gly, and Ser.In some embodiments, LAcomprises -N (RN) (C2alkylene-O) y1YbC (O) -, wherein RN is H, y1 is an integer from 1 to 10, and Yb is C1-C3 alkylene. In some embodiments, the -N (RN) (C2alkyleneYa) y1YbC (O) -is -NH (C2alkyleneO) 2C1alkyleneC (O) (OEG) , -NH (C2alkyleneO) C2alkyleneC (O) (PEG1) , -NH (C2alkyleneO) 3C2alkyleneC (O) (PEG3) , or -NH (C2alkyleneO) 6C2alkyleneC (O) (PEG6) . In some embodiments, each Y is independently selected from the group consisting of: Ahx, Cya, Gla, Gly, D-Ala, Ala, D-Val, Val, D-Leu, Leu, D-Phe, Phe, D-Pro, Pro, D-Met, Met, D-Trp, Trp, D-Thr, Thr, D-Tyr, Tyr, D-Nle, Nle, D-Ser, Ser, D-Asp, Asp, D-Glu, Glu, D-γGlu, γGlu, OEG and PEG1. In some embodiments, each Y is independently selected from the group consisting of: Gly, D-Asp, Asp, D-Glu, Glu, D-γGlu, γGlu, and OEG. In some embodiments, n is an integer of 1-10. In some embodiments, n is an integer of 1-5.In some embodiments, LA is a divalent linker comprising 1 to 5 Asp. In some embodiments, LA is a divalent linker comprising – (Asp) 2-5–. In some embodiments, LA is a divalent linker comprising – (D-Asp) 2-5–. In some embodiments, LA comprises 2 to 5 Asp, and wherein the 2 to 5 Asp is non-continuous in LA. In some embodiments, LA is a bond, -γGlu-γGlu-, -Glu-γGlu-, -Asp-, -Asp-Asp-, -γGlu-, -Gly-Ser-Gly-, -Asp-Asp-Asp-, -γGlu-γGlu-OEG-OEG-, -Asp-Asp-Gly-Gly-Gly-, -Asp-, -Glu-Glu-, - (D-Asp) - (D-Asp) -, -Gly-Gly-, -Asp-Asp-Asp-Asp-, -Cya-, -Gla-, -eLys-eLys-, -Ahx-Ahx-, -Gly-Ser-Gly-, or -Asp-Asp-OEG-. In some embodiments, LA is -Asp-Asp-, -Asp-Asp-Asp-, - (D-Asp) - (D-Asp) -, or -Asp-Asp-Asp-Asp-.In some embodiments, T comprises one or more amino acid residues each independently selected from the group consisting of Lys, D-Lys, ornithine (Orn) , homo-lysine, 2, 3-diaminopropionic acid (Dap) , 2, 4-diaminobutyric acid (Dab) , cysteine, homo-cysteine, glutamine, glutamic acid, asparagine, aspartic acid, 3, 5-bis (aminomethyl) benzoic acid (Bab) , 4-aminomethylphenylalaline (Amp) , 4R-4-aminoproline (Apr) , 4- (2-aminoethoxy) phenylalanine, 4-aminopiperidine-4-carboxylic acid (Apc) , and 2- ( (1, 3-diaminopropan-2-yl) oxy) acetic acid (Dpa) . In some embodiments, T is Lys, D-Lys, Amp, Apr, or Bab. In some embodiments, T comprises Lys or D-Lys. In some embodiments, when T comprises any of the amino acid residue selected from the group consisting of Lys, D-Lys, Orn, homo-lysine, 2, 3-diaminopropionic acid (Dap) , 2, 4-diaminobutyric acid (Dab) , cysteine, homo-cysteine, glutamine, glutamic acid, asparagine, aspartic acid, 4R-4-aminoproline (Apr) , and 4- (2-aminoethoxy) phenylalanine; then A is conjugated toα amino group of T. In some embodiments, when T comprises a Lys or D-Lys; then A is conjugated toα amino group of the Lys or D-Lys.In some embodiments, A is a fatty acid moiety. In some embodiments, A is a saturated fatty acid moiety. In some embodiments, A is a fatty monoacid moiety. In some embodiments, A is an unsubstituted or substituted C8-C18 fatty monoacid moiety. In some embodiments, A is an unsubstituted or substituted C10-C16 fatty monoacid moiety. In some embodiments, A is an unsubstituted or substituted C10 fatty monoacid moiety. In some embodiments, A is an unsubstituted or substituted C12 fatty monoacid moiety. In some embodiments, A is an unsubstituted or substituted C14 or a C16 fatty monoacid moiety. In some embodiments, A is -C (O) Aa, wherein Aa is unsubstituted or substituted C3-C23 alkyl. In some embodiments, Aa is C7 alkyl, C8 alkyl, C9 alkyl, C10 alkyl, C11 alkyl, C12 alkyl, C13 alkyl, C14 alkyl, C15 alkyl, C16 alkyl, or C17 alkyl, each of which is unsubstituted or substituted.In some embodiments, LZ is a bond or a divalent linker: – (X) m-, wherein: m is an integer of 1-20, and each X is independently selected from the group consisting of an amino acid residue and -N (RN) (C2alkyleneXa) x1XbC (O) , wherein RN is H or C1-6 alkyl, wherein Xa is -O-, -S-, -NH-, or -N (C1-6 alkyl) -, wherein x1 is an integer from 1 to 10, and wherein Xb is C1-3 alkylene.In some embodiments, LZ is a divalent linker comprising one or more amino acid residues. In some embodiments, the amino acid residues are neutral. In some embodiments, LZ comprises one or more amino acid residues each independently selected from the group consisting of alanine (Ala, A) , asparagine (Asn, N) , glutamine (Gln, Q) , glycine (Gly, G) , isoleucine (Ile, I) , leucine (Leu, L) , methionine (Met, M) , phenylalanine (Phe, F) , proline (Pro, P) , serine (Ser, S) , threonine (Thr, T) , tryptophan (Trp, W) , tyrosine (Tyr, Y) , valine (Val, V) , pyrrolysine (Pyl, O) , pyrroline-carboxy-lysine (PCL) , NR5C5alkyleneC (O) (Ahx) , norleucine (Nle) , norvaline (Nva) , 2-aminooctanoic acid (Aoc) , 2-naphthylalanine (2-Nal) , 3- (trifluoromethyl) phenylalanine (TFP) , homophenylalanine (hPhe) , cyclohexylalanine (Cha) , 1-naphthylalanine (1-Nal) , 4-benzoyl-L-phenylalanine (Bpa) , 2-methoxy-4-vinylphenylalanine (MvF) , 4-fluorophenylalanine (4-F-Phe) , 4-phenyl-2, 3-dihydroxy-6-nitrophenylalanine (pNIPA) , 2- (2-naphthyl) alanine (2-Nal-ala) , 4- (4-propoxyphenyl) alanine (Ppa) , 4-carboxyphenylalanine (4-CPA) , 4-butylphenylalanine (Bua) , 2-nitrophenylalanine (2-Npa) , 4-azidophenylalanine (4-AzF) , 2- (4-nitrophenyl) ethylalanine (2-Npe) , 3-iodo-L-tyrosine (Ity) , and 5, 5, 5-trifluoroleucine (TFL) . In some embodiments, LZ comprise one or more neutral amino acid residues, wherein each neutral amino acid residue is independently Gly, D-Pro, Pro, D-Ser or Ser. In some embodiments, LZ comprise one or more Gly.In some embodiments, LZcomprises -N (RN) (C2alkyleneXa) x1XbC (O) , wherein RN is H, x1 is an integer from 1 to 10, and Xb is C1-C3 alkylene. In some embodiments, RN is H. In some embodiments, LZ comprises one or more moieties each independently selected from -NH (C2alkyleneO) 2C1alkyleneC (O) (OEG) , -NH (C2alkyleneO) C2alkyleneC (O) (PEG1) , -NH (C2alkyleneO) 3C2alkyleneC (O) (PEG3) , or -NH (C2alkyleneO) 6C2alkyleneC (O) (PEG6) . In some embodiments, each X is independently selected from the group consisting of Ahx, Gly, D-Ala, Ala, D-Val, Val, D-Leu, Leu, D-Phe, Phe, D-Pro, Pro, D-Met, Met, D-Trp, Trp, D-Thr, Thr, D-Tyr, Tyr, D-Nle, Nle, D-Ser, Ser, OEG and PEG1. In some embodiments, each X is independently selected from the group consisting of Gly, Pro, Ser, and OEG. In some embodiments, m is an integer of 1-15. In some embodiments, m is an integer of 1-10. In some embodiments, m is an integer of 1-6.In some embodiments, LZ is a divalent linker comprising 1 to 6 OEG. In some embodiments, LZ is a divalent linker comprising 1 to 6 Gly. In some embodiments, LZ is – (Gly) 2-5–. In some embodiments, LZ comprises 2 to 5 Gly, and the 2 to 5 Gly is non-continuous. In some embodiments, LZ is a bond, -OEG-OEG-, -OEG-, -Gly-Gly-Gly-, -Gly-Ser-Gly-Ser-Gly-Ser-, -Pro-Gly-Pro-Gly-Pro-Gly-, -γGlu-γGlu -OEG-OEG-, -Asp-Asp-Gly-Gly-Gly-, -Gly-Gly-Gly-Gly-Gly-Gly-, -Gly-Tyr-Gly-, -Gly-Ser-Gly-, -Gly-, or -Gly-Gly-. In some embodiments, LZ is -Gly-Gly-Gly-.In some embodiments, E comprises a chemotherapeutic agent, a toxin, an immunomodulator, a diagnostic agent, a radionuclide, or a chelating group. In some embodiments, E comprises a radionuclide selected from the group consisting of14C , 15N , 18F , 75Br , 76Br , 77Br, 123I , 124I , 125I , 131I , 35S, 18F, 211At, 32P, 33P, and 125I. In some embodiments, E comprises a chelating group derived from a chelating agent. In some embodiments, the chelating agent is selected from 1, 4, 7-Triazacyclononane (TACN) , 1, 4, 7-triazacyclononane-triacetic acid (NOTA) , 1, 4, 7-triazacyclononane-N-succinic acid-N', N"-diacetic acid (NOTASA) , 1, 4, 7-triazacyclononane-N-glutamic acid-N', N"-diacetic acid (NODAGA) , 1, 4, 7-triazacyclononane-N, N', N"-tris (methylenephosphonic) acid (NOTP) , 1, 4, 7, 10-tetraazacyclododecane (
[0012] aneN4) (cyclen) , 1, 4, 7, 10-tetraazacyclotridecane (
[0013] aneN4) , 1, 4, 7, 11-tetraazacyclotetradecane (iso-cyclam) , 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) , 2- (1, 4, 7, 10-tetraazacyclododecan-1-yl) acetate (DO1A) , 2, 2'- (1, 4, 7, 10-tetraazacyclododecane-1, 7-diyl) diacetic acid (DO2A) , 2, 2', 2"- (1 , 4, 7, 10-tetraazacyclododecane-1 , 4, 7-triyl) triacetic acid (DO3A) , 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetra (methanepnosphonic acid) (DOTP) , 1, 4, 7, 10-tetraazacyclododecane-1, 7-di (methanephosphoriic acid) (DO2P) , 1 , 4, 7, 10-tetraazacyclododecane-1, 4, 7-tri (methanephosphonic acid) (DO3P) , 1, 4, 7, 10-tetraazacyclo-decane-1 -glutamic acid-4, 7, 10-triacetic acid (DOTAGA) , 1, 4, 7, 10-tetraazacyclodecane-1 -succinic acid-4, 7, 10-triacetic acid (DOTASA) , 1, 4, 8, 11-tetraazacyclotetradecane (
[0014] aneN4) (cyclam) , 1, 4, 8, 12-tetraazacyclopentadecane (
[0015] aneN4) , 1, 5, 9, 13-tetraazacyclohexadecane (
[0016] aneN4) , 1, 4-ethano-1, 4, 8, 11-tetraazacyclo-tetradecane (et-cyclam) , 1, 4, 8, 11-tetraazacyclotetradecane-1, 4, 8, 1 1-tetraacetic acid (TETA) , 2- (1, 4, 8, 11 -tetraazacyclotetradecane-1-y I) acetic acid (TE1A) , 2, 2'- (1, 4, 8, 11-tetraazacyclotetradecane-1, 8-diyl) diacetic acid (TE2A) , 4, 11-bis (carboxy methyl) -1, 4, 8, 11-tetraazabicyclo [6.6.2] -hexadecane (CB-TE2A) , 3, 6, 10, 13, 16, 19-hexaazabicyclo [6.6.6] icosane (Sar) , 1, 4, 7, 10-tetra- (2-carbamoyl-methyl) -cyclododecane (TCMC) , N, N′-bis [ (6-carboxy-2-pyridil) methyl] -4, 13-diaza-18-crown-6 (macropa) , phthalocyanines, porphyrins, PCTA (3, 6, 9, 15-tetraazabicyclo [9.3.1] pentadeca-1 (15) , 11, 13-triene-3, 6, 9-triacetic acid) , DEPA (7- [2- (biscarboxymethylamino) ethyl] -4, 10-biscarboxymethyl-1, 4, 7, 10-tetraazacyclododec-1-yl-acetic acid) , DTPA (1, 1, 4, 7, 7-diethylenetriaminepentaacetic acid) , CHX-DTPA (cyclohexane-1, 2-diamineN, N, N′, N′-tetraacetate) , BATPA (1, 2-bis [2-aminophenoxy] ethane-N, N, N′, N′-tetraacetic acid) , TTHA (triethylenetetramineN, N, N′, N″, N″′, N″′-hexaacetic acid) , HBED (N, N′-bis [2-hydroxybenzyl] ethylenediamine-N, N′-diacetic acid) , EGTA (ethylene glycol bis [2-aminoethyl ether] -N, N, N′, N′-tetraacetic acid) , EDTMP (ethylenediamine tetra- [methylene phosphonic acid] ) , TRAP (triazacyclononate phosphinic acids) , SHBED (N, N′-bis [2-hydroxy-5-sulfobenzyl] ethylenediaminediacetic acid) , H6Sbbpen (N, N′-bis- [2-hydroxy-5-sulfonylbenzyl] -N, N′-bis [2-methylpyridyl] ethylenediamine) , THP (Tris (3, 4-hydroxypyridinone) , DFO (deferoxamine) , FSC (Fusarinine) , 6SS (N, N′-bis [2, 2-dimethyl-2-mercaptoethyl] ethylenediamine-N, N′-diacetic acid) , ECC (ethylenecysteamine cysteine) , ECD (ethyl cysteinate dimer) , NETA ( [2- {4, 7-biscarboxymethyl (1, 4, 7) triazacyclonona-1-yl-ethyl} carbonylmethylamino] acetic acid, THPN (Tetrakis (3-Hydroxy-4-Pyridinone) ) , H2dedpa (1, 2- [ {6- (carboxylato-) pyridin-2-yl} methylamino] -ethane) , H4octapa (N, N′-bis [6-carboxy-2-pyridylmethyl] -ethylenediamine-N, N′-diacetic acid) , H2bispa2 (6, 6′- [ {9-hydroxy-1, 5-bis-(methoxycarbonyl) -2, 4-di (pyridin-2-yl) -3, 7-diazabicyclo [3.3.1] nonane-3, 7-diyl} bis (methylene) ] dipicolinic acid) , DOTMP (1, 4, 7, 10-Tetraazacyclododecane-1, 4, 7, 10-tetrayl-tetrakis (methylphosphonic acid) ) , PEPA (1, 4, 7, 10, 13-pentaazocyclopentadecane pentaacetic acid) , HEHA (1, 4, 7, 10, 13, 16-hexaazocyclooctadecane hexaacetic acid) , H2hox, H2CHXhox, H2octox, H2pyhox, H4neunopa, TETPA, H4pypa, H4py4pa, DTPAm, EGTAm, ampam, Me-3, 2-HOPO, 3, 4, 3- (LI-1, 2-HOPO) , and macrocyclic tetrapthalimide. In some embodiments, the chelating group is derived from DOTA or DOTAGA.In some embodiments, the radionuclides are each independently a radioactive isotope of As, Se, K, Sc, Ti, Cr, Mn, Fe, Co, Ni, Cu, Ga, Ge, Rb, Sr, Y, Zr, Nb, Tc, Rh, Pd, In, Sn, Sb, Zn, Ta, W, Re, Os, Ir, Pt, Au, Hg, Tl, Pb, Bi, Po, Fr, Pm, a lanthanide, an actinide, Mg, Al, Ca, Cd, or Ba. In some embodiments, the lanthanide is Lu, Sm, Ho, or Tb. In some embodiments, the actinide is Ac, Th, or U. In some embodiments, the one or more radionuclides are each independently selected from the group consisting of99Tc, 99mTc, 188Re, 186Re, 153Sm, 66Ga, 67Ga, 68Ga, 111In, 123In, 59Fe, 63Zn, 52Fe, 52Mn, 45Ti, 60Cu, 61Cu, 67Cu, 64Cu, 62Cu, 82Rb, 195mPt, 191mPt, 193mPt, 117mSn, 89Zr, 177Lu, 18F, 188Re, 186Re, 153Sm, 66Ho, 86Y , 87Y , 90Y, 89Sr, 153Gd, 159Gd, 225Ac, 212Bi, 213Bi, 198Au, 199Au, 193mPt, 197Pt, 103Pd, 109Pd, 105Rh, 101mRh, 103mRh, 223Ra, 224Ra, 97Ru, 227Th, 229Th, 161Tb, 149Tb, 203Pb, 212Pb, 201TI, 119Sb, 58mCo, 55Co, 57Co, 47Sc, 149Pm, 142Pr, 161Ho, 166Ho, 175Yb, and 51Cr. In some embodiments, E is 177Lu-DOTA-, 177Lu-DOTAGA-, 225Ac-DOTA-, or225Ac-DOTAGA-.In some embodiments, Z is:wherein:u is 0 or 1;R0 is C1-C6 alkyl substituted with one C6-C10 aryl, and the C6-C10 aryl is optionally substituted with one or more substituents, each substituent is independently halogen or NO2;R1 is C1-C6 alkyl substituted with one C6-C10 aryl, wherein the C6-C10 aryl is optionally substituted with one or more substituents, each substituent is independently -OH, -O (C1-C6 alkyl) , or -N (Ra) C (O) R1a, and wherein R1a is a 3 to 8-membered heterocycle optionally substituted with one or more oxo;R2 is C1-C6 alkyl substituted with one C6-C10 aryl or 5-to 12-membered heteroaryl, wherein the C6-C10 aryl or 5-to 12-membered heteroaryl is optionally substituted with one or more substituents, each substituent is independently -OH, -O (C1-C6 alkyl) , or -N (Ra) C (O) NH (Ra) ;x is 0 or 1;Rx is -N (Ra) C (O) - (C6-C10 aryl) ;R3 is C1-C6 alkyl substituted with one or more -NH (Ra) ;R4 is C1-C6 alkyl substituted with one or more -OH;y is 0 or 1;Ry is C1-C6 alkyl substituted with one C6-C10 aryl;Rz is -OH orwherein Rz1 is C1-C6 alkyl substituted with one or more substituents each independently selected from the group consisting of -OH and C6-C10 aryl optionally substituted with one or more -OH; Rz2 is -COOH, -C (O) NH2, or C1-C6 alkyl substituted with one or more -OH; andRa, at each occurrence, is independently H or C1-C3 alkyl.In some embodiments, u is 1, and R0 is C1-C6 alkyl substituted with one phenyl, wherein the phenyl is unsubstituted or substituted with one or more halogen.In some embodiments, R1 is methyl substituted with one C6-C10 aryl, wherein the C6-C10 aryl is optionally substituted with one or more substituents, each substituent is independently -OH or -NHC (O) R1a, wherein R1a is 3 to 8-membered heterocycle optionally substituted with one or more oxo.In some embodiments, R2 is C1-C6 alkyl substituted with one C6-C10 aryl or 5-to 12-membered heteroaryl, wherein the C6-C10 aryl is optionally substituted with one or more substituents, each substituent is independently-OH or -NHC (O) NH2.In some embodiments, R3 is C1-C6 alkyl substituted with one or more NH2.In some embodiments, R4 is C1-C3 alkyl substituted with one or more -OH.In some embodiments, Z is:In some embodiments, Z is:wherein R3a is CH2OH, CO2H, or CONH2.In some embodiments, the compound comprises a structure of anyone selected from Table 1.In some embodiments, the compound provided herein is for use in imaging or diagnosing, or for use in therapy.In one aspect, provided herein is a pharmaceutical composition, comprising the compound provided herein, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.In one aspect, provided herein is a kit, comprising the compound of the compound provided herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition provided herein, and instructions for using the kit to diagnose a disease or disorder in a subject in need thereof.In one aspect, provided herein is a kit, comprising the compound provided herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition provided herein, and instructions for using the kit to treat a disease or disorder in a subject in need thereof.In one aspect, provided herein is a method of treating a disease or disorder in a subject in need thereof, comprising administering to the subject a pharmaceutical effective amount of the compound provided herein or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition provided herein. In some embodiments, the disease or disorder is cancer. In some embodiments, the cancer is a cancer with high expression of SSTR2. In some embodiments, the cancer is medullary thyroid carcinoma (MTC) , a small cell lung cancer (SCLC) or a neuroendocrine tumor.In one aspect, provided herein is a method of inhibiting proliferative activity in a cell, comprising administering an effective amount of one or more compounds provided herein, or a salt thereof.In one aspect, provided herein is a method of imaging a tissue in a subject by administering an imaging effective amount of the compound provided herein, or a pharmaceutically acceptable salt thereof, to a subject in need thereof and applying an imaging technique to detect emitted gamma rays.In one aspect, provided herein is a method of diagnosing cancer in subject by administering a diagnostic effective amount of the compound provided herein, or a pharmaceutically acceptable salt thereof, and applying an imaging technique to detect emitted gamma rays.BRIEF DESCRIPTION OF THE DRAWINGSThe drawings illustrate certain embodiments of the features and advantages of this disclosure. These embodiments are not intended to limit the scope of the appended claims in any manner.FIG. 1 illustrates biodistribution of the radioisotope at 24h after administration of the exemplary 177Lu labeled compounds of the present application in different organs / tissues of H524 tumor bearing mice.FIG. 2A and FIG. 2B illustrate biodistribution of the radioisotope at different time points after administration of177Lu labeled Compound 027 versus 177Lu labeled DOTATATE in NET AR42J xenograft mice model.FIG. 3A and FIG. 3B illustrate biodistribution of the radioisotope at different time points after administration of177Lu labeled Compound 027 versus 177Lu labeled DOTATATE in SCLC H524 xenograft mice model.FIG. 4A and FIG. 4B illustrate mice SPECT / CT imaging results at 4h after administration of the exemplary 177Lu labeled compound of the present application, with or without 1000-fold extra amount of non-labeled DOTATATE, in AR42J tumor bearing mice.FIG. 5A and FIG. 5B illustrate in vivo efficacy studies of177Lu labeled Compound 027 in AR42J xenograft mice model.FIG. 6A-FIG. 6C illustrate in vivo efficacy of177Lu labeled Compound 027 after initial treatment of177Lu labeled reference compound.FIG. 7A and FIG. 7B illustrate in vivo efficacy studies of177Lu labeled Compound 027 in H524 xenograft mice model.FIG. 8A and FIG. 8B illustrate in vivo efficacy studies of177Lu labeled Compound 027 in H69 xenograft mice model.FIG. 9 illustrates biodistribution of the radioisotope at different time points after administration of225Ac labeled Compound 027 in NET AR42J xenograft model.FIG. 10A and FIG. 10B illustrate in vivo efficacy studies of225Ac labeled Compound 027 in AR42J rat pancreatic cancer cell xenograft model.FIG. 11 illustrates PET / CT imaging study of68Ga labeled Compound 027.DETAILED DESCRIPTIONThe present application provides a compound comprising three functional units, a Somatostatin type 2 receptor (SSTR2) binding moiety, an effector moiety, and a fatty acid moiety, which are connected via a trivalent moiety. Also provided is a method of using such a compound. The compounds described herein have displayed promising therapeutic potentials. The present invention is based, at least in part, on the surprising discovery that the compounds provided herein, when compared to traditional SSTR2 binding-moiety-including molecules such as DOTATATE, i) display higher binding affinity to SSTR2 in vitro and in vivo; and ii) provide higher uptake in SSTR2-expresssing tumors while maintain fast systemic clearance in vivo, therefore enable more effective tumor-targeted drug delivery and can potentially achieve larger therapeutic window. Such favorable profile renders the compounds provided herein particularly useful in diagnosing or treating a broad range of diseases characterized by high expression of SSTR2.I. DefinitionAs used in the present specification, the following words and phrases are generally intended to have the meanings as set forth below, except to the extent that the context in which they are used indicates otherwise.As used herein, “about” a parameter or value includes and describes that parameter or value per se. For example, “about X” includes and describes X per se.The singular forms “a” and “the” include plural references unless the context clearly dictates otherwise. Thus, e.g., reference to “the compound” includes a plurality of such compounds and reference to “the assay” includes reference to one or more compounds and equivalents thereof known to those skilled in the art.“Alkyl” refers to an unbranched or branched saturated hydrocarbon chain. As used herein, alkyl may have 1 to 20 carbon atoms (i.e., C1-20 alkyl) , 8 to 20 carbon atoms (i.e., C8-20 alkyl) , 10 to 18 carbon atoms (i.e., C10-18 alkyl) , 10 to 16 carbon atoms (i.e., C10-16 alkyl) or 12 to 16 carbon atoms (i.e., C12-16 alkyl) .The term “cycloalkyl” , as used herein, refers to a non-aromatic (e.g., saturated or partially unsaturated) carbocyclic ring moiety. The term “cycloalkyl” encompasses monocyclic ring moieties and polycyclic ring moieties, wherein the polycyclic moieties may be fused, bridged, or spiro. Cycloalkyl includes any polycyclic carbocyclic ring moiety comprising at least one non-aromatic ring, regardless of the point of attachment to the remainder of the molecule. As used herein, cycloalkyl includes rings having, for example, 3 to 20 annular carbon atoms (i.e., a C3-20 cycloalkyl) , 3 to 16 annular carbon atoms (i.e., a C3-16cycloalkyl) , 3 to 14 annular carbon atoms (i.e., C3-14cycloalkyl) , 3 to 12 annular carbon atoms (i.e., a C3-12cycloalkyl) , 3 to 10 annular carbon atoms (i.e., a C3-10cycloalkyl) , 3 to 8 annular carbon atoms (i.e., a C3-8cycloalkyl) , 3 to 6 annular carbon atoms (i.e., a C3-6cycloalkyl) , or 3 to 5 annular carbon atoms (i.e., a C3-5cycloalkyl) .The term “aryl” , as used herein, refers to an aromatic (e.g., fully unsaturated) carbocyclic ring moiety. The term “aryl” encompasses monocyclic ring moieties and polycyclic fused-ring moieties. As used herein, aryl encompasses ring moieties having, for example, 6 to 20 annular carbon atoms (i.e., C6-20aryl) , 6 to 16 annular carbon atoms (i.e., C6-16aryl) , 6 to 14 annular carbon atoms (i.e., C6-14 aryl) , 6 to 12 annular carbon atoms (i.e., C6-12 aryl) , or 6 to 10 annular carbon atoms (i.e., C6-10aryl) . Examples of aryl moieties include, but are not limited to, phenyl, naphthyl, and anthryl.The term “heteroaryl” , as used herein, refers to an aromatic (e.g., fully unsaturated) ring moiety that has one or more (e.g., 1, 2, 3, 4, or 5) annular heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. The term “heteroaryl” includes both monocyclic ring moieties and polycyclic fused-ring moieties. As used herein, a heteroaryl may have, for example, 5 to 20 annular atoms (i.e., a 5-to 20-membered heteroaryl) , 5 to 16 annular atoms (i.e., a 5-to 16-membered heteroaryl) , 5 to 14 annular atoms (i.e., a 5-to 14-membered heteroaryl) , 5 to 12 annular atoms (i.e., a 5-to 12-membered heteroaryl) , 5 to 10 annular atoms (i.e., a 5-to 10-membered heteroaryl) , 5 to 8 annular atoms (i.e., a 5-to 8-membered heteroaryl) , or 5 to 6 annular atoms (i.e., a 5-to 6-membered heteroaryl) , each independently having 1 to 5 ring heteroatoms, 1 to 4 ring heteroatoms, 1 to 3 ring heteroatoms, 1 to 2 ring heteroatoms, or 1 ring heteroatom independently selected from nitrogen, oxygen and sulfur. Any monocyclic or polycyclic aromatic ring moiety comprising one or more annular heteroatoms is considered a heteroaryl, regardless of the point of attachment to the remainder of the molecule (i.e., the heteroaryl moiety may be attached to the remainder of the molecule through any annular carbon or any annular heteroatom of the heteroaryl moiety) . Any aromatic ring, having a single or multiple fused rings, containing at least one heteroatom, is considered a heteroaryl regardless of the attachment to the remainder of the molecule (i.e., through any one of the fused rings) . Heteroaryl does not encompass or overlap with aryl as defined above.The term “heterocyclyl” , as used herein, refers to a non-aromatic (e.g., saturated or partially unsaturated) cyclic moiety that has one or more (e.g., 1, 2, 3, 4, or 5) annular heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. The term “heterocyclyl” includes both monocyclic and polycyclic ring moieties, wherein the polycyclic ring moieties may be fused, bridged, or spiro. Any non-aromatic monocyclic or polycyclic ring moiety comprising at least one annular heteroatom is considered a heterocyclyl, regardless of the point of attachment to the remainder of the molecule (i.e., the heterocyclyl moiety may be attached to the remainder of the molecule through any annular carbon or any annular heteroatom of the heterocyclyl moiety) . Further, the term heterocyclyl is intended to encompass any polycyclic ring moiety comprising at least one annular heteroatom wherein the polycyclic ring moiety comprises at least one non-aromatic ring, regardless of the point of attachment to the remainder of the molecule. As used herein, a heterocyclyl may have, for example, 3 to 20 annular atoms (i.e., a 3-to 20-membered heterocyclyl) , 3 to 16 annular atoms (i.e., a 3-to 16-membered heterocyclyl) , 3 to 14 annular atoms (i.e., a 3-14 membered heterocyclyl) , 3 to 12 annular atoms (i.e., a 3-to 12-membered heterocyclyl) , 3 to 10 annular atoms (i.e., a 3-to 10-membered heterocyclyl) , 3 to 8 annular atoms (i.e., a 3-to 8-membered heterocyclyl) , 3 to 6 annular atoms (i.e., a 3-to 6-membered heterocyclyl) , 3 to 5 annular atoms (i.e., a 3-to 5-membered heterocyclyl) , 5 to 8 annular atoms (i.e., a 5-to 8-membered heterocyclyl) , or 5 to 6 annular atoms (i.e., a 5-to 6-membered heterocyclyl) , each independently having 1 to 5 ring heteroatoms, 1 to 4 ring heteroatoms, 1 to 3 ring heteroatoms, 1 to 2 ring heteroatoms, or 1 ring heteroatom independently selected from nitrogen, oxygen and sulfur.“Halogen” or “halo” includes fluoro, chloro, bromo, and iodo.“Oxo” refers to the moiety =O.The terms “optional” or “optionally” means that the subsequently described event or circumstance may or may not occur. The term “optionally substituted” refers to any one or more hydrogen atoms on the designated atom or group may or may not be replaced by a moiety other than hydrogen. “Optionally substituted” unless otherwise specified means that a group may be unsubstituted or substituted by one or more (e.g., 1, 2, 3, 4 or 5) of the substituents listed for that group in which the substituents may be the same or different. In one embodiment, an optionally substituted group has one substituent. In another embodiment, an optionally substituted group has two substituents. In another embodiment, an optionally substituted group has three substituents. In some embodiments, an optionally substituted group has more than one substituents, wherein each substituent is independently selected. In another embodiment, an optionally substituted group has four substituents. In some embodiments, an optionally substituted group has 1 to 2, 1 to 3, 1 to 4, 1 to 5, 2 to 3, 2 to 4, or 2 to 5 substituents. In one embodiment, an optionally substituted group is unsubstituted. The substituents may be the same or different. Where there are multiple substituents within a moiety or compound, it is to be understood that each substituent may be selected independently of each other substituent.An optional substituent, as used herein, may be selected from the group consisting of C6-C24 aryl, C5-C24 heteroaryl, hydroxyl, C1-C20 alkoxy, C6-C24 aryloxy, cyano, halogen, nitro, C1-C20 fluoroalkoxy, and amino, which encompasses –NH2 and mono-, di-, and tri-substituted amino groups, and the protected derivatives thereof, or is selected from the group consisting of -X, -OR’ , -SR’ , -NH2, -N (R’ ) (Rop) , -N (Rop) 3, =NR’ , -CX3, -CN, -NO2, -NR’ C (=O) H, -NR’ C (=O) Rop, -NR’C (=O) Rop, -C (=O) R’ , -C (=O) NH2, -C (=O) N (R’ ) Rop , -S (=O) 2Rop, -S (=O) 2NH2, -S (=O) 2N (R’ ) Rop, -S (=O) 2NH2, -S (=O) 2N (R’ ) Rop, , -S (=O) 2OR’ , -S (=O) Rop, -OP (=O) (OR’ ) (ORop) , -OP (OH) 3, -P (=O) (OR’ ) (ORop) , -PO3H2, -C (=O) R’ , -C (=S) Rop, -CO2R’ , -C (=S) ORop, -C (=O) SR’ , -C (=S) SR’ , -C (=S) NH2, -C (=S) N (R’ ) (Rop) 2, -C (=NR’ ) NH2, -C (=NR’ ) N (R’ ) Rop, and salts thereof, wherein each X is independently selected from the group consisting of halogens: -F, -Cl, -Br, and -I; and wherein each Rop is independently selected from the group consisting of C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C6-C24 aryl, C3-C24 heterocyclyl, C5-C24 heteroaryl, a protecting group, and a prodrug moiety or two of Rop together with the heteroatom to which they are attached defines a C3-C24 heterocyclyl; and R’ is hydrogen or Rop, wherein Ropis selected from the group consisting of C1-C20 alkyl, C6-C24 aryl, C3-C24 heterocyclyl, C5-C24 heteroaryl, and a protecting group.In some embodiments, optional substituents that are present are each independently selected from the group consisting of -X, -OH, -ORop, -SH, -SRop, -NH2, -NH (Rop) , -NR’ (Rop) 2, -N (Rop) 3, =NH, =NRop, -CX3, -CN, -NO2, -NR’ C (=O) H, NR’ C (=O) Rop, –CO2H, -C (=O) H, -C (=O) Rop, -C (=O) NH2, -C (=O) NR’ Rop, -S (=O) 2Rop, -S (=O) 2NH2, -S (=O) 2N (R’ ) Rop, -S (=O) 2NH2, -S (=O) 2N (R’ ) (Rop) , -S (=O) 2OR’ , -S (=O) Rop, -C (=S) Rop, -C (=S) NH2, -C (=S) N (R’ ) Rop, -C (=NR’ ) N (Rop) 2, and salts thereof, wherein each X is independently selected from the group consisting of -F and -Cl, Rop is in some embodiments selected from the group consisting of C1-C6 alkyl, C6-C10 aryl, C3-C10 heterocyclyl, C5-C10 heteroaryl, and a protecting group; and R’ is independently selected from the group consisting of hydrogen, C1-C6 alkyl, C6-C10 aryl, C3-C10 heterocyclyl, C5-C10 heteroaryl, and a protecting group, independently selected from Rop.In some embodiments, optional substituents that are present are each independently selected from the group consisting of -X, -Rop, -OH, -ORop, -NH2, -NH (Rop) , -N (Rop) 2, -N (Rop) 3, -CX3, -NO2, -NHC (=O) H, -NHC (=O) Rop, -C (=O) NH2, -C (=O) NHRop, -C (=O) N (Rop) 2, -CO2H, -CO2Rop, -C (=O) H, -C (=O) Rop, -C (=O) NH2, -C (=O) NH (Rop) , -C (=O) N (Rop) 2, -C (=NR’ ) NH2, -C (=NR’ ) NH (Rop) , -C (=NR’ ) N (Rop) 2, a protecting group and salts thereof, wherein each X is –F; Rop is independently selected from the group consisting of C1-C6 alkyl, C6-C10 aryl, C5-C10 heteroaryl and a protecting group; and R’ is selected from the group consisting of hydrogen, C1-C6 alkyl and a protecting group, independently selected from Rop.The term “radionuclide” as used herein refers to any atom or ion capable of undergoing radioactive decay. The term radionuclide is used synonymously herein with radioactive nuclide, radioisotope, and radioactive isotope.The term “chelating group” as used herein is chelator capable of complexing with a radionuclide.As used herein, “fatty acid moiety” , refers to a fatty acid that connects to the rest of the compoundvia a covalent bond. In some embodiments, fatty acid moiety is a fatty acid that connects to the rest of the compound via a covalent bond (e.g., an amide bond) formed by a carboxylic group of the fatty acid. In some embodiments, “fatty monoacid” may refer to a fatty acid that has only a single carboxylic group. In some embodiments, the fatty monoacid moiety connects to the rest of the compound via a covalent bond (e.g., an amide bond) formed by the single carboxylic group of the fatty monoacid. In some embodiments, the fatty monoacid moiety has the formula -C (O) Aa, wherein Aa is unsubstituted or substituted alkyl that is no longer substituted with -COOH.As used herein, “treatment” or “treating” is an approach for obtaining a beneficial or desired result, such as a clinical result. For purposes of this disclosure, beneficial or desired results include, but are not limited to, alleviation of a symptom and / or diminishment of the extent of a symptom and / or preventing a worsening of a symptom associated with a disease or condition. In one variation, beneficial or desired clinical results include, but are not limited to, alleviation of a symptom and / or diminishment of the extent of a symptom and / or preventing a worsening of a symptom associated with a disease.The term “effective amount” as used herein, refers to a sufficient amount of at least one agent being administered to achieve a desired result, e.g., to image at least one cell or tissue, or to diagnose a disease or disorder, or to treat a disease or disorder. In certain instances, the method is in vitro, and the desired result may comprise certain desired alteration of cells or biological processes. In certain instances, the method is in vivo, and the result may comprise a reduction and / or alleviation of the signs, symptoms, or causes of a disease. In certain instances, the result is a death of or decrease in the growth of at least one abnormally proliferating cell, e.g., a cancer cell.In certain instances, an “effective amount” is considered in the context of therapeutical uses and may be optionally referred to as “therapeutically effective amount” . A “therapeutically effective amount” refers to an amount of the compound or the composition comprising a compound or salt thereof as set forth herein sufficient to produce a desired therapeutic outcome and / or required to provide a clinically significant decrease in a disease.“An individual” or “asubject” as used herein intends a mammal, including but not limited to a primate, human, bovine, horse, feline, canine, or rodent. In one variation, the individual or subject is a human.As used herein, by “pharmaceutically acceptable” or “pharmacologically acceptable” is meant a material that is not biologically or otherwise undesirable, e.g., the material may be incorporated into a pharmaceutical composition administered to a patient without causing any significant undesirable biological effects or interacting in a deleterious manner with any of the other components of the composition in which it is contained. Pharmaceutically acceptable carriers or excipients have preferably met the required standards of toxicological and manufacturing testing and / or are included on the Inactive Ingredient Guide prepared by the U.S. Food and Drug administration.“Pharmaceutically acceptable salts” are those salts which retain at least some of the biological activity of the free (non-salt) compound and which can be administered as drugs or pharmaceuticals to an individual. Such salts, for example, include: (1) acid addition salts, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or formed with organic acids such as acetic acid, trifluoroacetic acid, oxalic acid, propionic acid, succinic acid, maleic acid, tartaric acid and the like; (2) salts formed when an acidic proton present in the parent compound either is replaced by a metal ion, e.g., an alkali metal ion, an alkaline earth ion, or an aluminum ion; or coordinates with an organic base. Acceptable organic bases include ethanolamine, diethanolamine, triethanolamine and the like. Acceptable inorganic bases include aluminum hydroxide, calcium hydroxide, potassium hydroxide, sodium carbonate, sodium hydroxide, and the like. Further examples of pharmaceutically acceptable salts include those listed in Berge et al., Pharmaceutical Salts, J. Pharm. Sci. 1977 Jan; 66 (1) : 1-19. Pharmaceutically acceptable salts can be prepared in situ in the manufacturing process, or by separately reacting a purified compound of the disclosure in its free acid or base form with a suitable organic or inorganic base or acid, respectively, and isolating the salt thus formed during subsequent purification.The term “excipient” as used herein means an inert or inactive substance that may be used in the production of a drug or pharmaceutical, such as a tablet containing a compound of the disclosure as an active ingredient. Various substances may be embraced by the term excipient, including without limitation any substance used as a binder, disintegrant, coating, compression / encapsulation aid, cream or lotion, lubricant, solutions for parenteral administration, materials for chewable tablets, sweetener or flavoring, suspending / gelling agent, or wet granulation agent.In some embodiments, the amino acid used herein, unless otherwise specified, encompasses naturally occurring amino acids, unnaturally occurring amino acids, chemically modified naturally or unnaturally occurring amino acids, D enantiomers of the naturally or unnaturally occurring amino acid residues or the modified amino acid residues, amino acid residues derived from a naturally or unnaturallyβ-amino acid or aγ-amino acid. In some embodiments, “unnatural amino acid” , as used herein, refers to an amino acid that is not a naturally occurring amino acid and is obtained synthetically or by modification of a natural amino acid. In some embodiments, “naturally occurring amino acid” as used herein refers to amino acids that occur naturally and are encoded by the genetic code, as well as those encoded amino acids that are later modified in vivo. It is understood that any of the amino acids or amino acid residues described herein may, in some embodiments, connect to one or more amino acids or amino acid residues described herein via a covalent peptide bond.A “stereoisomer” refers to a compound made up of the same atoms bonded by the same bonds but having different three-dimensional structures, which are not interchangeable. The present disclosure contemplates various stereoisomers and mixtures thereof and includes “enantiomers, ” which refers to two stereoisomers whose molecules are nonsuperimposeable mirror images of one another and “diastereomers, ” which refers to stereoisomers that have at least two asymmetric atoms, but which are not mirror-images of each other.It is understood that aspects and embodiments described herein as “comprising” include “consisting of” and “consisting essentially of” embodiments.II. CompoundIn one aspect, provided herein is a compound comprising a SSTR2 binding moiety, an effector moiety (e.g., a radioactive effector moiety) , and a fatty acid moiety, which are connected via a trivalent moiety. In some embodiments, the SSTR2 binding moiety of the compound provided herein may direct the compound to bind to the SSTR2 expressed in certain cells, and the effector moiety may be used to kill or image the cells. In some embodiments, the cells are tumor cells that express SSTR2.In some embodiments, the fatty acid moiety and / or one or more of the linker moieties in the compound provided herein can increase the potency of the compound as compared to one without the fatty acid moiety and / or linker moieties, such as compound DOTATATE. Said increased potency includes but is not limited to higher binding affinity against human SSTR2, increased tumor uptake while fast systemic clearance, and a combination thereof. In some embodiments, the fatty acid moiety in the compound provided herein can increase the potency of the compound as compared to one without the fatty acid moiety. In some embodiments, one or more of the linker moieties including LA, LZ and LE in the compound provided herein can increase the potency of the compound as compared to one without any of the linker moiety (ies) .DOTATATE (also known as DOTA-TATE, DOTA-octreotate, oxodotreotide, DOTA-(Tyr3) -octreotate, and DOTA-0-Tyr3-Octreotate) is an eight amino acid long peptide, with a covalently bonded DOTA bifunctional chelator. The chemical structure of DOTATATE is:In some embodiments, the compound described herein or the pharmaceutically acceptable salt thereof shows increased potency such as higher binding affinity against human SSTR2, increased tumor uptake while fast systemic clearance, and any combination thereof, as compared to DOTATATE or radionuclide complex thereof.In some embodiments, the compound described herein or a pharmaceutically acceptable salt thereof has higher binding affinity against human SSTR2 as compared to DOTATATE or radionuclide complex thereof. In some embodiments, the compound or a pharmaceutically acceptable salt thereof has higher binding affinity against human SSTR2 by at least two folds as compared to DOTATATE or radionuclide complex thereof. In some embodiments, the compounds described herein or a pharmaceutically acceptable salt thereof has higher binding affinity against human SSTR2 by at least 4 folds as compared to DOTATATE or radionuclide complex thereof. In some embodiments, the compounds described herein or a pharmaceutically acceptable salt thereof has higher binding affinity against human SSTR2 by at least 8 folds as compared to DOTATATE or radionuclide complex thereof.In some embodiments, the compound provided herein is a compound of Formula (I) :wherein:T is a trivalent moiety,Z is a somatostatin receptor 2 (SSTR2) binding moiety, wherein Z is conjugated to T via a linker LZ,E is an effector moiety, wherein E is conjugated to T via a linker LE,A is an unsubstituted or substituted fatty acid moiety, wherein A is conjugated to T via a linker LA, andLZ, LE, and LA are each independently a bond or a divalent linker.In some embodiments, A is a fatty monoacid moiety. In some embodiments, A is an unsubstituted or substituted C8-C18 fatty monoacid moiety, optionally an unsubstituted or substituted C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, or C18 fatty monoacid moiety. In some embodiments, LA comprises one or more amino acid residues, N (RN) (C2alkyleneO) 2C1alkyleneC (O) , -N (RN) (C2alkyleneO) C2alkyleneC (O) , -N (RN) (C2alkyleneO) 3C2alkyleneC (O) , or -N (RN) (C2alkyleneO) 6C2alkyleneC (O) , wherein RN is H or C1-C6 alkyl. In some embodiments, RN is H. In some embodiments, RN is methyl, ethyl, or propyl. In some embodiments, LA is a divalent linker comprising 1 to 5 Asp. In some embodiments, LZ is a divalent linker comprising one or more amino acid residues, OEG, PEG1, PEG3, or PEG6. In some embodiments, LZ is a divalent linker comprising 1 to 6 Gly. Hence in some embodiments, A is an unsubstituted or substituted C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, or C18 fatty monoacid moiety, LA is a divalent linker comprising 1 to 5 Asp, and LZ is a divalent linker comprising 1 to 6 Gly.In some embodiments, the compounds described herein has a negative net charge after complexing with radionuclides including but not limited to 177Lu, 225Ac, and 111In, when the net charge is counted at physiological pH conditions and the charge of the radionuclide-chelator unit is counted as zero for trivalent-radionuclide-DOTA complex and -1 for trivalent radionuclide-DOTAGA complex. In some embodiments, the compounds described herein, after complexing with radionuclides, has a net charge of -1 to -8, such as any of -1, -2, -3, -4, -5, -6, -7, or -8, when the net charge is counted as aforementioned. In some embodiments, the compounds described herein, which comprises at least one radionuclide such as 177Lu, has a net charge of -1 to -5, such as about any of -1, -2, -3, -4, or -5.Each component of the compound provided herein is further described below.Trivalent linker TIn some embodiments, T may be any moiety that is capable of connecting to at least three groups. In some embodiments, T may be any moiety that comprises at least three terminal functional groups and each terminal functional group connects with one of the linking moieties. The at least three terminal functional groups can be the same or different.In some embodiments, T comprises one or more amino acid residues. In some embodiments, T could bind to LZ, LE, and LA via the N-terminal of an amino acid, the C-terminal of an amino acid, and the side chain of an amino acid, wherein the N-terminal, C-terminal, and the side chain may or may not belong to the same amino acid. In some embodiments, T comprises 1, 2, 3, 4, or 5 amino acids. In some embodiments, T comprises one or more amino acid residues each independently selected from the group consisting of Lys, D-Lys, ornithine (Orn) , homo-lysine, 2, 3-diaminopropionic acid (Dap) , 2, 4-diaminobutyric acid (Dab) , cysteine, homo-cysteine, glutamine, glutamic acid, asparagine, aspartic acid, 3, 5-bis (aminomethyl) benzoic acid (Bab) , 4-aminomethylphenylalaline (Amp) , 4R-4-aminoproline (Apr) , 4- (2-aminoethoxy) phenylalanine, 4-aminopiperidine-4-carboxylic acid (Apc) , and 2- ( (1, 3-diaminopropan-2-yl) oxy) acetic acid (Dpa) . In some embodiments, T comprises Lys, D-Lys, Amp, Apr, or Bab. In some embodiments, T comprises Lys or D-Lys. In some embodiments, T is Lys or D-Lys. In some embodiments, T is a single amino acid.In some embodiments, when T comprises any of the amino acid residue selected from the group consisting of Lys, D-Lys, Orn, homo-lysine, 2, 3-diaminopropionic acid (Dap) , 2, 4-diaminobutyric acid (Dab) , cysteine, homo-cysteine, glutamine, glutamic acid, asparagine, aspartic acid, 4R-4-aminoproline (Apr) , and 4- (2-aminoethoxy) phenylalanine; then A is conjugated toα amino group of T. In some embodiments, when T comprises a Lys or D-Lys; then A is conjugated toα amino group of the Lys or D-Lys.In some embodiments, T is Lys and the compound of Formula (I) is a compound of Formula (I-A) or (I-B) :In some embodiments, T is D-Lys and the compound of Formula (I) is a compound of Formula (I-A-a) or (I-B-a) :In some embodiments, T is L-Lys and the compound of Formula (I) is a compound of Formula (I-A-b) or (I-B-b) :In some embodiments, T is Amp and the compound of Formula (I) is a compound of Formula (I-C) or (I-D) :In some embodiments, T is Bab and the compound of Formula (I) is a compound of Formula (I-E) :In some embodiments, T is Apr and the compound of Formula (I) is a compound of Formula (I-F) or Formula (I-G) :In some embodiments, T is Dab and the compound of Formula (I) is a compound of Formula (I-H) or (I-I) :Linker LAIn some embodiments, LA is a bond or any divalent linker between T and A. In some embodiments, LA is a bond or a divalent linker: – (Y) n–,wherein:n is an integer of 1-20, andeach Y is independently selected from the group consisting of an amino acid residue and -N (RN) (C2alkyleneYa) y1YbC (O) , wherein RN is H or C1-C6 alkyl, wherein Ya is -O-, -S-, -NH-, or -N (C1-C6 alkyl) -, wherein y1 is an integer from 1 to 10, and wherein Yb is C1-C3 alkylene.In some embodiments, LA comprises one or more amino acid residues. In some embodiments, LA comprises one or more amino acid residues and LA may be connected to A and T via either the backbone or the side chain. In some embodiments, LA comprises one or more (e.g., an integer from 1 to 20, from 1 to 15, or from 1 to 10, or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) amino acid residues, each independently selected from the group consisting of alanine (Ala, A) , asparagine (Asn, N) , aspartic acid (Asp, D) , glutamine (Gln, Q) , glutamic acid (Glu, E) , γGlu, glutamine (Gln) , glycine (Gly, G) , isoleucine (Ile, I) , leucine (Leu, L) , εLys, methionine (Met, M) , phenylalanine (Phe, F) , proline (Pro, P) , serine (Ser, S) , threonine (Thr, T) , tryptophan (Trp, W) , tyrosine (Tyr, Y) , valine (Val, V) , pyrrolysine (Pyl, O) , pyrroline-carboxy-lysine (PCL) , gamma-carboxyglutamic acid (Gla) , NR5C5alkyleneC (O) (Ahx) , Cysteic acid (Cya) , norleucine (Nle) , norvaline (Nva) , 2-aminooctanoic acid (Aoc) , 2-naphthylalanine (2-Nal) , 3-(trifluoromethyl) phenylalanine (TFP) , homophenylalanine (hPhe) , cyclohexylalanine (Cha) , 1-naphthylalanine (1-Nal) , 4-benzoyl-L-phenylalanine (Bpa) , 2-methoxy-4-vinylphenylalanine (MvF) , 4-fluorophenylalanine (4-F-Phe) , 4-phenyl-2, 3-dihydroxy-6-nitrophenylalanine (pNIPA) , 2- (2-naphthyl) alanine (2-Nal-ala) , 4- (4-propoxyphenyl) alanine (Ppa) , 4-carboxyphenylalanine (4-CPA) , 4-butylphenylalanine (Bua) , 2-nitrophenylalanine (2-Npa) , 4-azidophenylalanine (4-AzF) , 2- (4-nitrophenyl) ethylalanine (2-Npe) , 3-iodo-L-tyrosine (Ity) , and 5, 5, 5-trifluoroleucine (TFL) , or a D enantiomer thereof.In some embodiments, LA comprises one or more (e.g., an integer from 1 to 20, from 1 to 15, or from 1 to 10, or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) negatively charged amino acid residues, wherein each amino acid residue is independently and optionally selected from the group consisting of D-Asp, Asp, D-Glu, Glu, D-γGlu, γGlu and Cya.In some embodiments, LA comprises one or more (e.g., an integer from 1 to 20, from 1 to 15, or from 1 to 10, or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) D-Asp, Asp, or any combination thereof.In some embodiments, LA comprises one or more (e.g., an integer from 1 to 20, from 1 to 15, or from 1 to 10, or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) neutral amino acid residues, wherein each amino acid residue is independently and optionally selected from the group consisting of Gly, D-Pro, Pro D-Ser, and Ser.In some embodiments, LA does not comprise Glu, D-Glu, D-γGlu, orγGlu.In some embodiments, LAcomprises -N (RN) (C2alkylene-O) y1-YbC (O) , wherein RN is H or C1-C6 alkyl, y1 is an integer from 1 to 10, and Yb is C1-C3 alkylene. In some embodiments, the -N (RN) (C2alkyleneYa) y1YbC (O) -is -N (RN) (C2alkyleneO) 2C1alkyleneC (O) , -N (RN) (C2alkyleneO) C2alkyleneC (O) , -N (RN) (C2alkyleneO) 3C2alkyleneC (O) , or -N (RN) (C2alkyleneO) 6C2alkyleneC (O) , wherein RN is H or C1-C6 alkyl. In some embodiments, RN is H. In some embodiments, RN is methyl, ethyl, or propyl. In some embodiments, the -N (RN) (C2alkyleneYa) y1YbC (O) -is -NH (C2alkyleneO) 2C1alkyleneC (O) (OEG) , -NH (C2alkyleneO) C2alkyleneC (O) (PEG1) , -NH (C2alkyleneO) 3C2alkyleneC (O) (PEG3) , or -NH (C2alkyleneO) 6C2alkyleneC (O) (PEG6) . In some embodiments, LAcomprises OEG. In some embodiments, LA comprises PEG1. In some embodiments, LA comprises PEG3. In some embodiments, LAcomprises PEG6. It should be noted that unless the directionality of a group is specified, no specific directionality is intended. For example, the -N (RN) (C2alkyleneYa) y1YbC (O) provided herein encompasses both -N (RN) (C2alkyleneYa) y1YbC (O) and -C (O) Yb (C2alkyleneYa) y1N (RN) .In some embodiments, n is an integer of 1-15. In some embodiments, n is an integer of 1-10. In some embodiments, n is an integer of 1-5. In some embodiments, n is any of 1, 2, or 3.In some embodiments, each Y is independently selected from the group consisting of: Ahx, Cya, Gla, Gly, D-Ala, Ala, D-Val, Val, D-Leu, Leu, D-Phe, Phe, D-Pro, Pro, D-Met, Met, D-Trp, Trp, D-Thr, Thr, D-Tyr, Tyr, D-Nle, Nle, D-Ser, Ser, D-Asp, Asp, D-Glu, Glu, D-γGlu, γGlu, Cya, OEG and PEG1. In some embodiments, each Y is independently selected from the group consisting of: Gly, D-Asp, Asp, D-Glu, Glu, D-γGlu, γGlu, Cya, and OEG.In some embodiments, LA is a divalent linker comprising 1 to 5 Asp. In some embodiments, LA is a divalent linker comprising – (Asp) 2-5–. In some embodiments, LA is a divalent linker comprising – (D-Asp) 2-5–. In some embodiments, LA comprises 2 to 5 Asp, and wherein the 2 to 5 Asp is non-continuous in LA. In some embodiments, the at least two Asp are not consecutive in LA. For example, there may be another amino acid or an OEG in between two Asp in LA.In some embodiments, LA is a bond, -γGlu-γGlu-, -Glu-γGlu-, -Asp-, -Asp-Asp-, -γGlu-, -Gly-Ser-Gly-, -Asp-Asp-Asp-, -γGlu-γGlu-OEG-OEG-, -Asp-Asp-Gly-Gly-Gly-, -Asp-, -Glu-Glu-, -D-Asp-D-Asp-, -Gly-Gly-, -Asp-Asp-Asp-Asp-, -Cya-, -Cya-Cya-, -Gla-, -eLys-eLys-, -Ahx-Ahx-, -Gly-Ser-Gly-, or -Asp-Asp-OEG-.In some embodiments, LA is a bond. In some embodiments, LA is -Asp-, -Asp-Asp-, -Asp-Asp-Asp-, -D-Asp-D-Asp-, -Cya-, -Cya-Cya-, or -Asp-Asp-Asp-Asp-.Fatty Acid Moiety AIn some embodiments, A is a fatty acid moiety. It is understood that a fatty acid moiety as described herein may, in some embodiments, connect to the rest of the compoundvia a covalent bond (e.g., an amide bond) formed by a carboxylic group of the fatty acid. In some embodiments, A is a fatty monoacid moiety, wherein the fatty monoacid moiety connects to the rest of the compoundvia a covalent bond (e.g., an amide bond) formed by the single carboxylic group of the fatty monoacid. In some embodiments, the fatty acid moiety has the formula -C (O) A1, wherein A1 is unsubstituted C3-C23 alkyl, or C3-C23 alkyl substituted with one or more -COOH, and optionally further substituted with other substituents. In some embodiments, the fatty acid moiety is a fatty monoacid moiety, which has the formula -C (O) Aa, wherein Aa is unsubstituted or substituted C3-C23 alkyl that is no longer substituted with -COOH. In some embodiments, Aa is unsubstituted C3-C23 alkyl. In some embodiments, fatty acid moiety may be saturated or unsaturated, and when unsaturated, may comprise any of 1, 2, 3, 4, or 5 double bonds or triple bonds. In some embodiments, A is a saturated fatty acid moiety.In some embodiments, A is an unsubstituted or substituted C4-C24 (e.g., C6-C24, C4-C20, C6-C20, C8-C20, C8-C28, or C10-C18) fatty monoacid moiety. In some embodiments, A is an unsubstituted or substituted C8-C18 fatty monoacid moiety. In some embodiments, A is an unsubstituted or substituted C10-C16 fatty monoacid moiety. In some embodiments, A is an unsubstituted or substituted C12-C16 fatty monoacid moiety. In some embodiments, A is an unsubstituted or substituted C8 fatty monoacid moiety. In some embodiments, A is an unsubstituted or substituted C9 fatty monoacid moiety. In some embodiments, A is an unsubstituted or substituted C10 fatty monoacid moiety. In some embodiments, A is an unsubstituted or substituted C11 fatty monoacid moiety. In some embodiments, A is an unsubstituted or substituted C12 fatty monoacid moiety. In some embodiments, A is an unsubstituted or substituted C13 fatty monoacid moiety. In so embodiments, A is an unsubstituted or substituted C14 fatty monoacid moiety. In some embodiments, A is an unsubstituted or substituted C15 fatty monoacid moiety. In some embodiments, A is an unsubstituted or substituted C16 fatty monoacid moiety. In some embodiments, A is an unsubstituted or substituted C17 fatty monoacid moiety. In some embodiments, A is an unsubstituted or substituted C18 fatty monoacid moiety.In some embodiments, A is -C (O) Aa, wherein Aa is unsubstituted or substituted C3-C23 alkyl. In some embodiments, Aa is C7 alkyl, C8 alkyl, C9 alkyl, C10 alkyl, C11 alkyl, C12 alkyl, C13 alkyl, C14 alkyl, C15 alkyl, C16 alkyl, or C17 alkyl, each of which is unsubstituted or substituted. In some embodiments, Aa is C7 alkyl, C8 alkyl, C9 alkyl, C10 alkyl, C11 alkyl, C12 alkyl, C13 alkyl, C14 alkyl, C15 alkyl, C16 alkyl, or C17 alkyl, each of which is unsubstituted. In some embodiments, Aa is C7 alkyl, C8 alkyl, C9 alkyl, C10 alkyl, C11 alkyl, C12 alkyl, C13 alkyl, C14 alkyl, C15 alkyl, C16 alkyl, or C17 alkyl, each of which is not substituted with -COOH.Linker LZIn some embodiments, LZ is a bond or any divalent linker between T and Z. In some embodiments, LZ is a bond or a divalent linker: – (X) m–,wherein:m is an integer of 1-20, andeach X is independently selected from the group consisting of an amino acid residue and -N (RN) (C2alkyleneXa) x1XbC (O) , wherein RN is H or C1-6 alkyl, wherein Xa is -O-, -S-, -NH-, or -N (C1-6 alkyl) -, wherein x1 is an integer from 1 to 10, and wherein Xb is C1-3 alkylene.In some embodiments, LZ comprises one or more amino acid residues. In some embodiments, LZ comprises one or more amino acid residues and LZ may be connected to Z and T via either the backbone or the side chain. In some embodiments, LZ is a divalent linker comprising one or more (e.g., an integer from 1 to 20, from 1 to 15, or from 1 to 10, or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) amino acid residues, each independently selected from the group consisting of alanine (Ala, A) , asparagine (Asn, N) , glutamine (Gln, Q) , glycine (Gly, G) , isoleucine (Ile, I) , leucine (Leu, L) , methionine (Met, M) , phenylalanine (Phe, F) , proline (Pro, P) , serine (Ser, S) , threonine (Thr, T) , tryptophan (Trp, W) , tyrosine (Tyr, Y) , valine (Val, V) , pyrrolysine (Pyl, O) , pyrroline-carboxy-lysine (PCL) , NR5C5alkyleneC (O) (Ahx) , norleucine (Nle) , norvaline (Nva) , 2-aminooctanoic acid (Aoc) , 2-naphthylalanine (2-Nal) , 3- (trifluoromethyl) phenylalanine (TFP) , homophenylalanine (hPhe) , cyclohexylalanine (Cha) , 1-naphthylalanine (1-Nal) , 4-benzoyl-L-phenylalanine (Bpa) , 2-methoxy-4-vinylphenylalanine (MvF) , 4-fluorophenylalanine (4-F-Phe) , 4-phenyl-2, 3-dihydroxy-6-nitrophenylalanine (pNIPA) , 2- (2-naphthyl) alanine (2-Nal-ala) , 4- (4-propoxyphenyl) alanine (Ppa) , 4-carboxyphenylalanine (4-CPA) , 4-butylphenylalanine (Bua) , 2-nitrophenylalanine (2-Npa) , 4-azidophenylalanine (4-AzF) , 2- (4-nitrophenyl) ethylalanine (2-Npe) , 3-iodo-L-tyrosine (Ity) , and 5, 5, 5-trifluoroleucine (TFL) .In some embodiments, LZ comprises one or more amino acid residues that are neutral. In some embodiments, LZ does not comprise negatively charged amino acid residue. In some embodiments, LZ comprise one or more (e.g., an integer from 1 to 20, from 1 to 15, or from 1 to 10, or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) neutral amino acid residues, wherein each neutral amino acid residue is independently Gly, D-Pro, Pro, D-Ser or Ser.In some embodiments, LZ comprise one or more (e.g., an integer from 1 to 20, from 1 to 15, or from 1 to 10, or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) Gly.In some embodiments, LZcomprises -N (RN) (C2alkyleneO) x1XbC (O) , wherein RN is H or C1-C6 alkyl, x1 is an integer from 1 to 10, and Xb is C1-C3 alkylene. In some embodiments, the -N (RN) (C2alkyleneXa) x1XbC (O) -is -N (RN) (C2alkyleneO) 2C1alkyleneC (O) , -N (RN) (C2alkyleneO) C2alkyleneC (O) , -N (RN) (C2alkyleneO) 3C2alkyleneC (O) , or -N (RN) (C2alkyleneO) 6C2alkyleneC (O) , wherein RN is H or C1-C6 alkyl. In some embodiments, RN is H. In some embodiments, RN is methyl, ethyl, or propyl. In some embodiments, LZcomprises one or more moieties each independently selected from the group consisting of NH (C2alkyleneO) 2C1alkyleneC (O) (OEG) , -NH (C2alkyleneO) C2alkyleneC (O) (PEG1) , -NH (C2alkyleneO) 3C2alkyleneC (O) (PEG3) , or -NH (C2alkyleneO) 6C2alkyleneC (O) (PEG6) . In some embodiments, LZ comprises OEG. In some embodiments, LA comprises PEG1. In some embodiments, LZcomprises PEG3. In some embodiments, LZcomprises PEG6.In some embodiments, m is an integer of 1-15. In some embodiments, m is an integer of 1-10. In some embodiments, m is an integer of 1-6. In some embodiments, m is any of 1, 2, or 3.In some embodiments, each X is independently selected from the group consisting of Ahx, Gly, D-Ala, Ala, D-Val, Val, D-Leu, Leu, D-Phe, Phe, D-Pro, Pro, D-Met, Met, D-Trp, Trp, D-Thr, Thr, D-Tyr, Tyr, D-Nle, Nle, D-Ser, Ser, OEG and PEG1. In some embodiments, each X is independently selected from the group consisting of Gly, Pro, Ser, and OEG.In some embodiments, LZ is a divalent linker comprising 1 to 6 Gly. In some embodiments, LZ is – (Gly) 2-5–. In some embodiments, LZ comprises 2 to 5 Gly, and the 2 to 5 Gly is non-continuous. In some embodiments, the at least two Gly are not consecutive in LZ. For example, there may be another amino acid or an OEG in between two Gly in LZ.In some embodiments, LZ does not comprise -C2alkyleneO-. In some embodiments, LZ does not comprise OEG. In some embodiments, LZdoes not comprise PEG3. In some embodiments, LZdoes not comprise PEG6.In some embodiments, LZ is a bond, -OEG-OEG-, -OEG-, -Gly-Gly-Gly-, -Gly-Ser-Gly-Ser-Gly-Ser-, -Pro-Gly-Pro-Gly-Pro-Gly-, -γGlu-γGlu -OEG-OEG-, -Asp-Asp-Gly-Gly-Gly-, -Gly-Gly-Gly-Gly-Gly-Gly-, -Gly-Tyr-Gly-, -Gly-Ser-Gly-, -Gly-, or -Gly-Gly-.In some embodiments, LZ is a bond. In some embodiments, LZ is -Gly-Gly-Gly-.Effector EIn some embodiments, E comprises a chemotherapeutic agent, a toxin, an immunomodulator, a diagnostic agent, a radionuclide, a chelating group, or any combination thereof.In some embodiments, E comprises one or more radionuclides, and each of which is independently a radioactive isotope of C, N, O, F, P, S, Cl, Br, I, Se, At. In some embodiments, the one or more radionuclides are each independently selected from the group consisting of 14C , 15N , 18F , 75Br , 76Br , 77Br, 123I , 124I , 125I , 131I , 35S, 18F, 211At, 32P, 33P, and 125I. In some embodiments, E comprises one or more radionuclides and the compound may be used for imaging, and the one or more radionuclides for use in imaging are selected from 18F or 123I. In some embodiments, E comprises one or more radionuclides and the compound may be used for killing a cell or treating a disease, and the one or more radionuclides are selected from 211At, 32P, 33P, or 125I.In some embodiments, E is connected to LE through any one of the available functional groups. In some embodiments, E comprises a chelating group comprising two or more carboxyl groups, and E is connected to LE through a carboxyl functional group.In some embodiments, E comprises a chelating group derived from a chelating agent, and the chelating agent is a cyclic bifunctional chelating group or an acyclic bifunctional chelating group capable of complexing one or more radionuclides.A person skilled in the art would appreciate that “achelating group derived from a chelating agent” as used herein refers to a chelating agent derivative formed after the chelating agent is connected to the trivalent group of the compound of Formula (I) via LE. For example, “achelating group derived from a chelating agent” may be a chelating agent without the “-OH” (or ester thereof) of an available carboxyl group (or ester thereof) on the chelating agent, without the “H” portion of an available amino group on the chelating agent, without the “NCS” portion of an available isothiocyanate on the chelating agent, without the “H” portion of an available maleimide group on the chelating agent, a chelating agent after an available acetylene group on the chelating agent has been reacted to connect to the trivalent group of the compound of formula I via LE, or a chelating agent after an available tetrazole group on the chelating agent has been reacted to connect to the trivalent group of the compound of Formula (I) via LE. For example, a person skilled in the art would appreciate that when E is a chelating group derived from a DOTA, one “-OH” from one of the four available carboxyl groups on DOTA is removed to form the connection to LE (or T when LE is a direct bond) in the compound of Formula (I) .In some embodiments, the chelating group is derived from a chelating agent selected from the group consisting of 1, 4, 7-Triazacyclononane (TACN) , 1, 4, 7-triazacyclononane-triacetic acid (NOTA) , 1, 4, 7-triazacyclononane-N-succinic acid-N', N"-diacetic acid (NOTASA) , 1, 4, 7-triazacyclononane-N-glutamic acid-N', N"-diacetic acid (NODAGA) , 1, 4, 7-triazacyclononane-N, N', N"-tris (methylenephosphonic) acid (NOTP) , 1, 4, 7, 10-tetraazacyclododecane (
[0012] aneN4) (cyclen) , 1, 4, 7, 10-tetraazacyclotridecane (
[0013] aneN4) , 1, 4, 7, 11-tetraazacyclotetradecane (iso-cyclam) , 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) , 2- (1, 4, 7, 10-tetraazacyclododecan-1-yl) acetate (DO1A) , 2, 2'- (1, 4, 7, 10-tetraazacyclododecane-1, 7-diyl) diacetic acid (DO2A) , 2, 2', 2"- (1 , 4, 7, 10-tetraazacyclododecane-1 , 4, 7-triyl) triacetic acid (DO3A) , 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetra (methanepnosphonic acid) (DOTP) , 1, 4, 7, 10-tetraazacyclododecane-1, 7-di (methanephosphoriic acid) (DO2P) , 1 , 4, 7, 10-tetraazacyclododecane-1, 4, 7-tri (methanephosphonic acid) (DO3P) , 1, 4, 7, 10-tetraazacyclo-decane-1 -glutamic acid-4, 7, 10-triacetic acid (DOTAGA) , 1, 4, 7, 10-tetraazacyclodecane-1 -succinic acid-4, 7, 10-triacetic acid (DOTASA) , 1, 4, 8, 11-tetraazacyclotetradecane (
[0014] aneN4) (cyclam) , 1, 4, 8, 12-tetraazacyclopentadecane (
[0015] aneN4) , 1, 5, 9, 13-tetraazacyclohexadecane (
[0016] aneN4) , 1, 4-ethano-1, 4, 8, 11-tetraazacyclo-tetradecane (et-cyclam) , 1, 4, 8, 11-tetraazacyclotetradecane-1, 4, 8, 1 1-tetraacetic acid (TETA) , 2- (1, 4, 8, 11 -tetraazacyclotetradecane-1-y I) acetic acid (TE1A) , 2, 2'- (1, 4, 8, 11-tetraazacyclotetradecane-1, 8-diyl) diacetic acid (TE2A) , 4, 11-bis (carboxy methyl) -1, 4, 8, 11-tetraazabicyclo [6.6.2] -hexadecane (CB-TE2A) , 3, 6, 10, 13, 16, 19-hexaazabicyclo [6.6.6] icosane (Sar) , 1, 4, 7, 10-tetra- (2-carbamoyl-methyl) -cyclododecane (TCMC) , N, N′-bis [ (6-carboxy-2-pyridil) methyl] -4, 13-diaza-18-crown-6 (macropa) , phthalocyanines, porphyrins, PCTA (3, 6, 9, 15-tetraazabicyclo [9.3.1] pentadeca-1 (15) , 11, 13-triene-3, 6, 9-triacetic acid) , DEPA (7- [2- (biscarboxymethylamino) ethyl] -4, 10-biscarboxymethyl-1, 4, 7, 10-tetraazacyclododec-1-yl-acetic acid) , DTPA (1, 1, 4, 7, 7-diethylenetriaminepentaacetic acid) , CHX-DTPA (cyclohexane-1, 2-diamineN, N, N′, N′-tetraacetate) , BATPA (1, 2-bis [2-aminophenoxy] ethane-N, N, N′, N′-tetraacetic acid) , TTHA (triethylenetetramineN, N, N′, N″, N″′, N″′-hexaacetic acid) , HBED (N, N′-bis [2-hydroxybenzyl] ethylenediamine-N, N′-diacetic acid) , EGTA (ethylene glycol bis [2-aminoethyl ether] -N, N, N′, N′-tetraacetic acid) , EDTMP (ethylenediamine tetra- [methylene phosphonic acid] ) , TRAP (triazacyclononate phosphinic acids) , SHBED (N, N′-bis [2-hydroxy-5-sulfobenzyl] ethylenediaminediacetic acid) , H6Sbbpen (N, N′-bis- [2-hydroxy-5-sulfonylbenzyl] -N, N′-bis [2-methylpyridyl] ethylenediamine) , THP (Tris (3, 4-hydroxypyridinone) , DFO (deferoxamine) , FSC (Fusarinine) , 6SS (N, N′-bis [2, 2-dimethyl-2-mercaptoethyl] ethylenediamine-N, N′-diacetic acid) , ECC (ethylenecysteamine cysteine) , ECD (ethyl cysteinate dimer) , NETA ( [2- {4, 7-biscarboxymethyl (1, 4, 7) triazacyclonona-1-yl-ethyl} carbonylmethylamino] acetic acid, THPN (Tetrakis (3-Hydroxy-4-Pyridinone) ) , H2dedpa (1, 2- [ {6- (carboxylato-) pyridin-2-yl} methylamino] -ethane) , H4octapa (N, N′-bis [6-carboxy-2-pyridylmethyl] -ethylenediamine-N, N′-diacetic acid) , H2bispa2 (6, 6′- [ {9-hydroxy-1, 5-bis-(methoxycarbonyl) -2, 4-di (pyridin-2-yl) -3, 7-diazabicyclo [3.3.1] nonane-3, 7-diyl} bis (methylene) ] dipicolinic acid) , DOTMP (1, 4, 7, 10-Tetraazacyclododecane-1, 4, 7, 10-tetrayl-tetrakis (methylphosphonic acid) ) , PEPA (1, 4, 7, 10, 13-pentaazocyclopentadecane pentaacetic acid) , HEHA (1, 4, 7, 10, 13, 16-hexaazocyclooctadecane hexaacetic acid) , H2hox, H2CHXhox, H2octox, H2pyhox, H4neunopa, TETPA, H4pypa, H4py4pa, DTPAm, EGTAm, ampam, Me-3, 2-HOPO, 3, 4, 3- (LI-1, 2-HOPO) , macrocyclic tetrapthalimide, or any derivative thereof. In some embodiments, E comprises a chelating group derived from DOTA or DOTAGA and is connected to L1 through any one of the available carboxyl functional groups.In some embodiments, E comprises a chelating group which further complexes with one or more radionuclide. In some embodiments, the radionuclides complexed with the chelating group are each independently a radioactive isotope of As, K, Sc, Ti, Cr, Mn, Fe, Co, Ni, Cu, Ga, Ge, Rb, Sr, Y, Zr, Nb, Tc, Rh, Pd, In, Sn, Sb, Zn, Ta, W, Re, Os, Ir, Pt, Au, Hg, Tl, Pb, Bi, Po, Fr, Pm, lanthanide (such as La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu) , an actinide (such as Ac, Th, U) , Mg, Al, Ca, Cd, or Ba. In some embodiments, the lanthanide is Lu, Sm, Ho, or Tb. In some embodiments, the actinide is Ac, Th, or U.In some embodiments, the one or more radionuclides complexed with the chelating group are each independently selected from the group consisting of 199Tc, 99mTc, 188Re, 186Re, 153Sm, 66Ga, 67Ga, 68Ga, 111In, 123In, 59Fe, 63Zn, 52Fe, 52Mn, 45Ti, 60Cu, 61Cu, 67Cu, 64Cu, 62Cu, 82Rb, 195mPt, 191mPt, 193mPt, 117mSn, 89Zr, 177Lu, 18F, 188Re, 186Re, 153Sm, 66Ho, 86Y , 87Y , 90Y, 89Sr, 153Gd, 159Gd, 225Ac, 212Bi, 213Bi, 198Au, 199Au, 193mPt, 197Pt, 103Pd, 109Pd, 105Rh, 101mRh, 103mRh, 223Ra, 224Ra, 97Ru, 227Th, 229Th, 161Tb, 149Tb, 203Pb, 212Pb, 201TI, 119Sb, 58mCo, 55 Co, 57Co, 47Sc, 149Pm, 142Pr, 161Ho, 166Ho, 175Yb, and 51Cr.In some embodiments, the compound provided herein may be used for imaging, and the one or more radionuclides complexed with the chelating group for use in imaging are selected from the group consisting of99mTc, 188Re, 186Re, 153Sm, 66Ga, 67Ga, 68Ga, 111In, 59Fe, 63Zn, 52Fe, 52Mn, 45Ti, 60Cu, 61Cu, 67Cu, 64Cu, 62Cu, 82Rb, 198Au, 199Au, 195mPt, 191mPt, 193mPt, 117mSn, 89Zr, 177Lu, 18F, 203Pb, 44Sc, 51Cr, 101mRh, and 166Ho.In some embodiments, the compound provided herein may be used for killing a cell or treating a disease, and the one or more radionuclides for killing a cell or treating a disease are selected from the group consisting of188Re, 186Re, 153Sm, 66Ho, 90Y, 89Sr, 111In, 153Gd, 225Ac, 212Bi, 213Bi, 60Cu, 61Cu, 67Cu, 64Cu, 62Cu, 198Au, 99Au, 195mPt, 193mPt, 197Pt, 117mSn, 103Pd, 105Rh, 103mRh, 177Lu, 223Ra, 224Ra, 227Th, 229Th, 149Tb, 161Tb, 203Pb, 212Pb, 201TI, 119Sb, 58mCo, 47Sc, 149Pm, 161Ho, 159Gd, 142Pr, 166Ho, and 175Yb. In some embodiments, the one or more radionuclides for use in therapy are selected from the group consisting of177Lu, 212Pb, and 225Ac. In some embodiments, the radionuclides for killing a cell or treating a disease is 177Lu or 225Ac. In some embodiments, the one or more radionuclides for killing a cell or treating a disease is 177Lu. In some embodiments, the one or more radionuclides for killing a cell or treating a disease is 225Ac.In some embodiments, E is 177Lu-DOTA-, 177Lu-DOTAGA-, 225Ac-DOTA-, or 225Ac-DOTAGA-.Linker LEIn some embodiments, LE is a bond or any divalent linker between T and E. In some embodiments, LE is a bond or a divalent linker: – (U) k–,wherein:k is an integer of 1-20, andeach U is independently selected from the group consisting of an amino acid residue and -N (RN) (C2alkyleneUa) k1UbC (O) , wherein RN is H or C1-6 alkyl, wherein Ua is -O-, -S-, -NH-, or -N (C1-6 alkyl) -, wherein k1 is an integer from 1 to 10, and wherein Ub is C1-3 alkylene.In some embodiments, LE comprises one or more amino acid residues. In some embodiments, LE comprises one or more amino acid residues and LE may be connected to E and T via either the backbone or the side chain. In some embodiments, LE is a divalent linker comprising one or more amino (e.g., an integer from 1 to 20, from 1 to 15, or from 1 to 10, or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) acid residues.In some embodiments, LE comprises -N (RN) (C2alkyleneUa) k1UbC (O) , wherein RN is H or C1-C6 alkyl, wherein Ua is -O-, -S-, -NH-, or -N (C1-C6 alkyl) -, wherein k1 is an integer from 1 to 10, and wherein Ub is C1-C3 alkylene. In some embodiments, the -N (RN) (C2alkyleneUa) k1UbC (O) is -N (RN) (C2alkyleneO) 2C1alkyleneC (O) , -N (RN) (C2alkyleneO) C2alkyleneC (O) , -N (RN) (C2alkyleneO) 3C2alkyleneC (O) , or -N (RN) (C2alkyleneO) 6C2alkyleneC (O) , wherein RN is H or C1-C6 alkyl. In some embodiments, RN is H. In some embodiments, RN is methyl, ethyl, or propyl. In some embodiments, LE comprises one or more moieties each independently selected from the group consisting of NH (C2alkyleneO) 2C1alkyleneC (O) (OEG) , -NH (C2alkyleneO) C2alkyleneC (O) (PEG1) , -NH (C2alkyleneO) 3C2alkyleneC (O) (PEG3) , or -NH (C2alkyleneO) 6C2alkyleneC (O) (PEG6) . In some embodiments, LEcomprises OEG. In some embodiments, LE comprises PEG1. In some embodiments, LE comprises PEG3. In some embodiments, LEcomprises PEG6.In some embodiments, k is an integer of 1-15. In some embodiments, k is an integer of 1-10. In some embodiments, k is an integer of 1-6. In some embodiments, k is any of 1, 2, or 3.In some embodiments, LE is a bond.SSTR2 Binding MoietyIn some embodiments, Z is a targeting moiety that is capable of specifically binding to human SSTR2. In some embodiments, the Z is connected to LZ through any one of its available functional groups. In some embodiments, Z comprises an amino functional group, and Z is connected to LZ through the amino functional group. In some embodiments, Z is:wherein:u is 0 or 1;R0 is C1-C6 alkyl substituted with one C6-C10 aryl, and the C6-C10 aryl is optionally substituted with one or more substituents, each substituent is independently halogen or NO2;R1 is C1-C6 alkyl substituted with one C6-C10 aryl, wherein the C6-C10 aryl is optionally substituted with one or more substituents, each substituent is independently -OH, -O (C1-C6 alkyl) , or -N (Ra) C (O) R1a, and wherein R1a is a 3 to 8-membered heterocycle optionally substituted with one or more oxo;R2 is C1-C6 alkyl substituted with one C6-C10 aryl or 5-to 12-membered heteroaryl, wherein the C6-C10 aryl or 5-to 12-membered heteroaryl is optionally substituted with one or more substituents, each substituent is independently -OH, -O (C1-C6 alkyl) , or -N (Ra) C (O) NH (Ra) ;x is 0 or 1;Rx is -N (Ra) C (O) - (C6-C10 aryl) ;R3 is C1-C6 alkyl substituted with one or more -NH (Ra) ;R4 is C1-C6 alkyl substituted with one or more -OH;y is 0 or 1;Ry is C1-C6 alkyl substituted with one C6-C10 aryl;Rz is -OH orwherein Rz1 is C1-C6 alkyl substituted with one or more substituents each independently selected from the group consisting of -OH and C6-C10 aryl optionally substituted with one or more -OH; Rz2 is -COOH, -C (O) NH2, or C1-C6 alkyl substituted with one or more -OH; andRa, at each occurrence, is independently H or C1-C3 alkyl.In some embodiments, u is 1, and R0 is C1-C6 alkyl (e.g., C1-C3 alkyl, methyl, ethyl, or propyl) substituted with one phenyl, wherein the phenyl is unsubstituted or substituted with one or more halogen or NO2. In some embodiments, u is 1, and R0 is methyl substituted with one phenyl, wherein the phenyl is unsubstituted or substituted with one or more halogen or NO2. In some embodiments, R0 isIn some embodiments, R1 is methyl substituted with one C6-C10 aryl (e.g., phenyl) , wherein the C6-C10 aryl is optionally substituted with one or more substituents, each substituent is independently -OH or -NHC (O) R1a, wherein R1a is 3 to 8-membered heterocycle (e.g., 3-to 6-memebered heterocycle) optionally substituted with one or more oxo. In some embodiments, R1 is methyl substituted with one phenyl, wherein the phenyl is substituted with one -OH. In some embodiments, R1 is methyl substituted with one phenyl, wherein the phenyl is substituted with one -NHC (O) R1a, wherein R1a is 3-to 6-memebered heterocycle optionally substituted with one or more oxo. In some embodiments, R1 is methyl substituted with one phenyl, wherein the phenyl is substituted with oneIn some embodiments, R1 isIn some embodiments, R2 is C1-C6 alkyl (e.g., C1-C3 alkyl, methyl, ethyl, or propyl) substituted with one C6-C10 aryl or 5-to 12-membered heteroaryl, each of which is optionally substituted with one or more substituents, each substituent is independently-OH or -NHC (O) NH2. In some embodiments, R2 is C1-C3 alkyl substituted with one phenyl, wherein the phenyl is optionally substituted with one or more -OH or -NHC (O) NH2. In some embodiments, R2 is C1-C3 alkyl substituted with one 5-to 12-membered heteroaryl, wherein the 5-to 12-membered heteroaryl is unsubstituted. In some embodiments, the 5-to 12-membered heteroaryl isIn some embodiments, R2 isIn some embodiments, R3 is C1-C6 alkyl substituted with one or more NH2. In some embodiments, R3 is -CH2CH2CH2CH2NH2.In some embodiments, x is 0. In some embodiments, x is 1. In some embodiments, Rx isIn some embodiments, y is 0. In some embodiments, y is 1. In some embodiments, Ry isIn some embodiments, R4 is C1-C3 alkyl substituted with one or more -OH. In some embodiments, R4 isIn some embodiments, Rz is -OH.In some embodiments, Rz isIn some embodiments, Rz1 is C1-C6 alkyl substituted with one or more -OH. In some embodiments, Rz1 isIn some embodiments, Rz1 is C6-C10 aryl optionally substituted with one or more -OH. In some embodiments, Rz1 is In some embodiments, Rz2 is -COOH. In some embodiments, Rz2 is C1-C6 alkyl substituted with one or more -OH. In some embodiments, Rz2 is -CH2OH. In some embodiments, Rz2 is -C (O) NH2. In some embodiments, Rz is -OH, In some embodiments, Z is:wherein R3a is CH2OH, CO2H, or CONH2.In some embodiments, Z is:In some embodiments of the compound of Formula (I) , at least one of the (i) - (vii) is satisfied:(i) LA comprises 1 to 5 Asp or D-Asp;(ii) LA does not comprise Glu, D-Glu, D-γGlu, orγGlu;(iii) A is a fatty monoacid moiety;(iv) A is C8-C16 fatty acid moiety;(v) LZ comprises 1 to 6 Gly; and(vi) LZ does not comprise -C2alkyleneO-;(vii) when T is D-Lys or Lys, LAisconjugated to the alpha amino group of T.In some embodiments, (i) and (ii) apply. In some embodiments, (i) and (iii) apply. In some embodiments, (i) and (iv) apply. In some embodiments, (i) and (v) apply. In some embodiments, (i) and (vi) apply. In some embodiments, (i) and (vii) apply. In some embodiments, (ii) and (iii) apply. In some embodiments, (ii) and (iv) apply. In some embodiments, (ii) and (v) apply. In some embodiments, (ii) and (vi) apply. In some embodiments, (ii) and (vii) apply. In some embodiments, (iii) and (iv) apply. In some embodiments, (iii) and (v) apply. In some embodiments, (iii) and (vi) apply. In some embodiments, (iii) and (vii) apply. In some embodiments, (iv) and (v) apply. In some embodiments, (iv) and (vi) apply. In some embodiments, (iv) and (vii) apply. In some embodiments, (v) and (vi) apply. In some embodiments, (v) and (vii) apply. In some embodiments, (vi) and (vii) apply. In some embodiments, (i) , (ii) , (iii) apply. In some embodiments, (i) , (ii) , (iv) apply. In some embodiments, (i) , (ii) , (v) apply. In some embodiments, (i) , (ii) , (vi) apply. In some embodiments, (i) , (ii) , (vii) apply. In some embodiments, (ii) , (iii) , (iv) apply. In some embodiments, (ii) , (iii) , (v) apply. In some embodiments, (ii) , (iii) , (vi) apply. In some embodiments, (ii) , (iii) , (vii) apply. In some embodiments, (iii) , (iv) , (v) apply. In some embodiments, (iii) , (iv) , (vi) apply. In some embodiments, (iii) , (iv) , (vii) apply. In some embodiments, (iv) , (v) , (vi) apply. In some embodiments, (iv) , (v) , (vii) apply. In some embodiments, (v) , (vi) , (vii) apply. In some embodiments, (i) , (ii) , (iii) , and (iv) apply. In some embodiments, (i) , (ii) , (iii) , and (v) apply. In some embodiments, (i) , (ii) , (iii) , and (vi) apply. In some embodiments, (i) , (ii) , (iii) , and (vii) apply. In some embodiments, (ii) , (iii) , (iv) , and (v) apply. In some embodiments, (ii) , (iii) , (iv) , and (vi) apply. In some embodiments, (ii) , (iii) , (iv) , and (vii) apply. In some embodiments, (iii) , (iv) , (v) , and (vi) apply. In some embodiments, (iii) , (iv) , (v) , and (vii) apply. In some embodiments, (iv) , (v) , (vi) and (vii) apply. In some embodiments, (i) , (ii) , (iii) , (iv) , and (v) apply. In some embodiments, (i) , (ii) , (iii) , (iv) , and (vi) apply. In some embodiments, (i) , (ii) , (iii) , (iv) , and (vii) apply. In some embodiments, (ii) , (iii) , (iv) , (v) and (vi) apply. In some embodiments, (ii) , (iii) , (iv) , (v) and (vii) apply. In some embodiments, (iii) , (iv) , (v) , (vi) and (vii) apply. In some embodiments, (i) , (iv) , (v) , (vi) and (vii) apply. In some embodiments, (ii) , (iv) , (v) , (vi) and (vii) apply. In some embodiments, (i) , (ii) , (iv) , (v) , and (vi) apply. In some embodiments, (i) , (ii) , (iv) , (v) , and (vii) apply. In some embodiments, (ii) , (iii) , (v) , (vi) , and (vii) apply. In some embodiments, (i) , (ii) , (iii) , (vi) and (vii) apply. In some embodiments, (i) , (ii) , (iv) , (vi) , and (vii) apply. In some embodiments, (i) , (ii) , (iii) , (iv) , (v) , and (vi) apply. In some embodiments, (ii) , (iii) , (iv) , (v) , (vi) and (vii) apply. In some embodiments, (i) , (ii) , (iii) , (iv) , (v) , (vi) , and (vii) apply.In some embodiments, provided herein is a compound of Formula (I) , wherein Z is a SSTR2 binding moiety; T is Lys, D-Lys, Amp, Apr, Dab, or Bab; E is an effector moiety comprising a chelating group derived from DOTA or DOTAGA complexed with one or more radionuclides; A is an unsubstituted or substituted C6-C24 fatty acid moiety, wherein A is conjugated to T via a linker LA through the alpha amino group of T; LZ, LE, and LA are each independently a bond or a divalent linker. In some embodiments, LA comprises 1 to 5 Asp or D-Asp; and LZ comprises 1 to 6 Gly. In some embodiments, LA comprises 1 to 5 Asp or D-Asp and LZ does not comprise -C2alkyleneO-. In some embodiments, LA comprises 1 to 5 Asp or D-Asp, LA does not comprise Glu, D-Glu, D-γGlu, orγGlu, and A is a fatty monoacid moiety. In some embodiments, LA comprises 1 to 5 Asp or D-Asp, LZ comprises 1 to 6 Gly, and LZ does not comprise -C2alkyleneO-. In some embodiments, A is a fatty monoacid moiety and LZ does not comprise -C2alkyleneO-. In some embodiments, A is a fatty monoacid moiety, and LZ comprises 1 to 6 Gly. In some embodiments, LA comprises 1 to 5 Asp or D-Asp, A is a C12 fatty monoacid moiety, wherein A is conjugated to T via a linker LA through the alpha amino group of T, LZ comprises 1 to 6 Gly, and LZ does not comprise -C2alkyleneO-. In some embodiments, T is D-Lys or Lys, LAisconjugated to the alpha amino group of T, and LA comprises 1 to 5 Asp or D-Asp. In some embodiments, T is Amp, Apr, or Bab, and LA comprises 1 to 5 Asp or D-Asp. In some embodiments, T is D-Lys or Lys, LAisconjugated to the alpha amino group of T, E comprises a chelating group derived from DOTA complexed with one or more radionuclides, and A is a fatty monoacid moiety. In some embodiments, T is D-Lys or Lys, LAisconjugated to the alpha amino group of T, E comprises a chelating group derived from DOTA complexed with one or more radionuclides, and A is a C8-C12 fatty monoacid moiety, wherein A is conjugated to T via a linker LA through the alpha amino group of T.In some embodiments, provided here is a compound of Formula (I) , wherein Z isT is Lys, D-Lys, Amp, Dab, Apr, or Bab; E is an effector moiety comprising a chelating group derived from DOTA or DOTAGA complexed with one or more radionuclides ; A is an unsubstituted or substituted C6-C24fatty acid moiety, wherein A is conjugated to T via a linker LA through the alpha amino group of T; LZ, LE, and LA are each independently a bond or a divalent linker. In some embodiments, LA comprises 1 to 5 Asp or D-Asp; and LZ comprises 1 to 6 Gly. In some embodiments, LA comprises 1 to 5 Asp or D-Asp and LZ does not comprise -C2alkyleneO-. In some embodiments, LA comprises 1 to 5 Asp or D-Asp, LA does not comprise Glu, D-Glu, D-γGlu, orγGlu, and A is a fatty monoacid moiety. In some embodiments, LA comprises 1 to 5 Asp or D-Asp, LZ comprises 1 to 6 Gly, and LZ does not comprise -C2alkyleneO-. In some embodiments, A is a fatty monoacid moiety, and LZ does not comprise -C2alkyleneO-. In some embodiments, A is a fatty monoacid moiety, and LZ comprises 1 to 6 Gly. In some embodiments, LA comprises 1 to 5 Asp or D-Asp, A is a C12 fatty monoacid moiety, wherein A is conjugated to T via a linker LA through the alpha amino group of T, LZ comprises 1 to 6 Gly, and LZ does not comprise -C2alkyleneO-. In some embodiments, T is D-Lys or Lys, LAisconjugated to the alpha amino group of T, and LA comprises 1 to 5 Asp or D-Asp. In some embodiments, T is Amp, Apr, or Bab, and LA comprises 1 to 5 Asp or D-Asp. In some embodiments, T is D-Lys or Lys, LAisconjugated to the alpha amino group of T, E comprises a chelating group derived from DOTA complexed with one or more radionuclides A, and A is a fatty monoacid moiety. In some embodiments, T is Lys, E comprises a chelating group derived from DOTA complexed with one or more radionuclides, and A is a C8-C12 fatty monoacid moiety, wherein A is conjugated to T via a linker LA through the alpha amino group of T.In some embodiments, provided here is a compound of Formula (I) , wherein Z is T is Lys, D-Lys, Dab, Amp, Apr, or Bab; E is an effector moiety comprising a chelating group derived from DOTA or DOTAGA complexed with one or more radionuclides; A is an unsubstituted or substituted C6-C24 fatty acid moiety, wherein A is conjugated to T via a linker LA through the alpha amino group of T; LZ, LE, and LA are each independently a bond or a divalent linker. In some embodiments, LA comprises 1 to 5 Asp or D-Asp; and LZ comprises 1 to 6 Gly. In some embodiments, LA comprises 1 to 5 Asp or D-Asp and LZ does not comprise -C2alkyleneO-. In some embodiments, LA comprises 1 to 5 Asp or D-Asp, LA does not comprise Glu, D-Glu, D-γGlu, orγGlu, and A is a fatty monoacid moiety. In some embodiments, LA comprises 1 to 5 Asp or D-Asp, LZ comprises 1 to 6 Gly, and LZ does not comprise -C2alkyleneO-. In some embodiments, A is a fatty monoacid moiety, and LZ does not comprise -C2alkyleneO-. In some embodiments, A is a fatty monoacid moiety, and LZ comprises 1 to 6 Gly. In some embodiments, LA comprises 1 to 5 Asp or D-Asp, A is a C12 fatty monoacid moiety, wherein A is conjugated to T via a linker LA through the alpha amino group of T, LZ comprises 1 to 6 Gly, and LZ does not comprise -C2alkyleneO-. In some embodiments, T is D-Lys or Lys, LAisconjugated to the alpha amino group of T, and LA comprises 1 to 5 Asp or D-Asp. In some embodiments, T is Amp, Apr, or Bab, and LA comprises 1 to 5 Asp or D-Asp. In some embodiments, T is D-Lys or Lys, LAisconjugated to the alpha amino group of T, E comprises a chelating group derived from DOTA complexed with one or more radionuclides, and A is a fatty monoacid moiety. In some embodiments, T is Lys, E comprises a chelating group derived from DOTA complexed with one or more radionuclides, and A is a C8-C12 fatty monoacid moiety, wherein A is conjugated to T via a linker LA through the alpha amino group of T.In some embodiments, provided herein is a compound of Formula (I-a) :wherein:T is a trivalent moiety selected from the group consisting of Lys, D-Lys, Amp, Dab, Apr, and Bab,Z is a somatostatin receptor 2 (SSTR2) binding moiety, wherein Z is conjugated to T via a linker LZ,E is an effector moiety comprising a chelating group derived from DOTA or DOTAGA complexed with one or more radionuclides, wherein E is conjugated to T via a linker LE,A is an unsubstituted or substituted C6-C24fatty acid moiety, wherein A is conjugated to T via a linker LA through the alpha amino group of T, andLZ, LE, and LA are each independently a bond or a divalent linker.In some embodiments of the compound of Formula (I-a) , T is D-Lys or Lys, LA is conjugated to the alpha amino group of T.In some embodiments of the compound of Formula (I-a) , LA comprises 1 to 5 Asp or D-Asp.In some embodiments of the compound of Formula (I-a) , LA comprises 1 to 5 Asp or D-Asp and LA does not comprise Glu, D-Glu, D-γGlu, orγGlu.In some embodiments of the compound of Formula (I-a) , LA comprises 1 to 5 Asp or D-Asp and A is a fatty monoacid moiety.In some embodiments of the compound of Formula (I-a) , LA does not comprise Glu, D-Glu, D-γGlu, orγGlu and A is a fatty monoacid moiety.In some embodiments of the compound of Formula (I-a) , LA comprises 1 to 5 Asp or D-Asp and LZ comprises 1 to 6 Gly.In some embodiments of the compound of Formula (I-a) , LA comprises 1 to 5 Asp or D-Asp and LZ does not comprise -C2alkyleneO-.In some embodiments of the compound of Formula (I-a) , LA comprises 1 to 5 Asp or D-Asp, LA does not comprise Glu, D-Glu, D-γGlu, orγGlu, and A is a fatty monoacid moiety.In some embodiments of the compound of Formula (I-a) , LA comprises 1 to 5 Asp or D-Asp, LZ comprises 1 to 6 Gly, and LZ does not comprise -C2alkyleneO-.In some embodiments of the compound of Formula (I-a) , A is a fatty monoacid moiety, and LZ does not comprise -C2alkyleneO-.In some embodiments of the compound of Formula (I-a) , A is a fatty monoacid moiety, and LZ comprises 1 to 6 Gly.In some embodiments of the compound of Formula (I-a) , LA comprises 1 to 5 Asp or D-Asp, A is a C12 fatty monoacid moiety, wherein A is conjugated to T via a linker LA through the alpha amino group of T, LZ comprises 1 to 6 Gly, and LZ does not comprise -C2alkyleneO-.In some embodiments, the compound of Formula (I) comprises a ligand moiety selected from the moieties in Table 1.Table 1 Structures of exemplary compounds of the present applicationAbbreviations:T: Threonine; C: Cysteine; K: Lysine; k: D-Lysine; w: D-Tryptophan; Y: Tyrosine; f: D-Phenylalanine; A: Alanine; G: Glycine; W: Tryptophan; Nle: Non-leucine; D: Aspartic acid; S: Serine; p: D-proline; R: Arginine:gE: gamma-Glutamic acid; eK: epsilon-Lysine-OH: C-terminal acid; -NH2: C-terminal amide; Thr (ol) : C-terminal alcohol[CXXXXC] : Disulfide bondDOTA: 1, 4, 7, 10-Tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid;DOTAGA: 2- [1, 4, 7, 10-Tetraazacyclododecane-4, 7, 10-trisacetic acid] -pentanedioic acidOEG: H2N- [CH2CH2O] 2-CH2CO2HIn some embodiments, provided herein is a pharmaceutical composition, comprising any of the compounds described herein, such as a compound of Formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.Also provided are stereoisomers, mixture of stereoisomers, tautomers, isotopically enriched analogs, and pharmaceutically acceptable salts of the compounds described herein, such as compound of Formula (I) , or variations thereof described herein.In the descriptions herein, it is understood that every description, variation, embodiment or aspect of a moiety may be combined with every description, variation, embodiment or aspect of other moieties the same as if each and every combination of descriptions is specifically and individually listed. For example, every description, variation, embodiment or aspect provided herein with respect to A of Formula (I) may be combined with every description, variation, embodiment or aspect of LZ of Formula (I) the same as if each and every combination were specifically and individually listed and such combinations are equally applicable to other formulae where permitted by the chemical structure. For another example, every description, variation, embodiment or aspect provided herein with respect to E of Formula (I) may be combined with every description, variation, embodiment or aspect of LA of Formula (I) the same as if each and every combination were specifically and individually listed and such combinations are equally applicable to other formulae where permitted by the chemical structure.The compounds disclosed herein, or their pharmaceutically acceptable salts, may include an asymmetric center and may thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that may be defined, in terms of absolute stereochemistry, as (R) -or (S) -. The present disclosure is meant to include all such possible isomers, as well as their racemic and optically pure forms. Optically active (+) and (-) , or (R) -and (S) -isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques, for example, chromatography and fractional crystallization. Conventional techniques for the preparation / isolation of individual enantiomers include chiral synthesis from a suitable optically pure precursor or resolution of the racemate (or the racemate of a salt or derivative) using, for example, chiral high pressure liquid chromatography (HPLC) . When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, and unless specified otherwise, it is intended that the compounds include both E and Z geometric isomers. In some embodiments, the compound of Formula (I) provided herein also encompasses stereoisomers of Formula (I) or variations thereof.The present disclosure also encompasses tautomers. Tautomers are in equilibrium with one another. For example, amide containing compounds may exist in equilibrium with imidic acid tautomers. Regardless of which tautomer is shown and regardless of the nature of the equilibrium among tautomers, the compounds are understood by one of ordinary skill in the art to comprise both amide and imidic acid tautomers. Thus, the amide containing compounds are understood to include their imidic acid tautomers. Likewise, the imidic acid containing compounds are understood to include their amide tautomers.Any compound or structure given herein, is also intended to represent unlabeled forms as well as isotopically labeled forms of the compounds. These forms of compounds may also be referred to as an “isotopically enriched analog. ” Isotopically labeled compounds have structures depicted herein, except that one or more atoms are replaced by an atom having a selected atomic mass or mass number. Examples of isotopes that can be incorporated into the disclosed compounds include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine, chlorine and iodine, such as 2H, 3H, 11C, 13C, 14C, 13N, 15N, 15O, 17O, 18O, 31P, 32P, 35S, 18F, 36Cl, 123I, and 125I, respectively. Various isotopically labeled compounds of the present disclosure, for example those into which radioactive isotopes such as 3H, 13C and 14C are incorporated. Such isotopically labeled compounds may be useful in metabolic studies, reaction kinetic studies, detection or imaging techniques, such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT) including drug or substrate tissue distribution assays or in radioactive treatment of patients. Such compounds may exhibit increased resistance to metabolism and are thus useful for increasing the half-life of any compound when administered to a mammal, particularly a human. Such compounds are synthesized by means well known in the art, for example by employing starting materials in which one or more hydrogens have been replaced by deuterium.Certain compounds disclosed herein contain one or more ionizable groups (groups from which a proton can be removed (e.g., -COOH) or added (e.g., amines) or which can be quaternized (e.g., amines) ) . All possible ionic forms of such molecules and salts thereof are intended to be included individually in the disclosure herein. With regard to salts of the compounds described herein, one of ordinary skill in the art can select from among a wide variety of available counterions those that are appropriate. In specific applications, the selection of a given anion or cation for preparation of a salt may result in increased or decreased solubility of that salt.In some embodiments, provided herein is a pharmaceutically acceptable salt of the compounds described herein. In some embodiments, the pharmaceutically acceptable salt is an acid addition salt or a base addition salt. The selection of a suitable salt may be made by aperson skilled in the art (see, for example, S.M. Berge, et al., “Pharmaceutical Salts, ” J. Pharm. Sci. 1977, 66, 1-19) .Descriptions of compounds of the present disclosure are limited by principles of chemical bonding known to those skilled in the art. Accordingly, where a group may be substituted by one or more of a number of substituents, such substitutions are selected so as to comply with principles of chemical bonding and to give compounds which are not inherently unstable and / or would be known to one of ordinary skill in the art as likely to be unstable under ambient conditions, such as aqueous, neutral, and several known physiological conditions. For example, a heterocycle or heteroaryl is attached to the remainder of the molecule via a ring heteroatom in compliance with principles of chemical bonding known to those skilled in the art thereby avoiding inherently unstable compounds.III. Method of useIn some aspects, provided herein is a compound of Formula (I) or a pharmaceutically acceptable salt thereof, for use in imaging or diagnosing, or for use in therapy, wherein the compound of Formula (I) can be any of the compounds or variations described herein.In some aspects, provided herein is a method of treating a disease or disorder in a subject in need thereof, comprising administering to the subject a pharmaceutical effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition, comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof. In some embodiments, the disease or disorder is cancer. In some embodiments, the cancer is a cancer with high expression of SSTR2. In some embodiments, the cancer is medullary thyroid carcinoma (MTC) , a small cell lung cancer (SCLC) , or a neuroendocrine tumor.In some embodiments, provided herein is a method of inhibiting proliferative activity in a cell, comprising administering an effective amount of one or more compounds of Formula (I) or a pharmaceutically acceptable salt thereof. In some embodiments, the cell expresses SSTR2 on its surface.In some embodiments, the compounds provided herein, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, or the pharmaceutical composition described herein, is cytotoxic and could kill or inhibit the growth of cancer cells. In some embodiments, provided herein is a method of killing cancer cells comprising contacting the cells with an effective amount of the compound described herein, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, or the pharmaceutical composition described herein, . In some embodiments, provided herein is a method of inhibiting the growth of the cancer cells comprising contacting the cells with an effective amount of the compound described herein, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, or the pharmaceutical composition described herein. In some embodiments, provided herein is a method of killing cancer cells in a human in need thereof comprising administering to the human a therapeutically effective amount of the compound described herein, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, or the pharmaceutical composition described herein. In some embodiments, provided herein is a method of inhibiting the growth of the cancer cells in a human in need thereof comprising administering to the human a therapeutically effective amount of the compound described herein, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, or the pharmaceutical composition described herein.In some embodiments, provided herein is a method of imaging a tissue in a subject by administering an imaging effective amount of one or more compounds of Formula (I) , or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, or the pharmaceutical composition described herein, to a subject in need thereof and applying an imaging technique to detect emitted gamma rays.In some embodiments, provided herein is a method of diagnosing cancer in a subject by administering a diagnostic effective amount of one or more compounds of Formula (I) , or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, or the pharmaceutical composition described herein, and applying an imaging technique to detect emitted gamma rays.IV. KitsAlso provided herein are kits for carrying out the methods described herein, which comprises one or more compounds described herein, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmacological composition comprising a compound described herein. The kits may employ any of the compounds disclosed herein. In one variation, the kit employs a compound described herein or a pharmaceutically acceptable salt thereof. The kits may be used for any one or more of the uses described herein, and, accordingly, may contain instructions for use in the diagnosis or treatment of a cancer.In some aspects, provided herein is a kit, comprising a compound of Formula (I) , or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, or the pharmaceutical composition described herein, and instructions for using the kit to diagnose a disease or disorder in a subject in need thereof.In some aspects, provided herein is a kit, comprising a compound of Formula (I) , or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, or the pharmaceutical composition described herein, and instructions for using the kit to treat a disease or disorder in a subject in need thereof.In some embodiments, the kit may comprise one or more containers comprising any compound described herein. Each component (if there is more than one component) can be packaged in separate containers or some components can be combined in one container where cross-reactivity and shelf-life permit. One or more components of a kit may be sterile and / or may be contained within sterile packaging.In some embodiments, the kit may comprise a set of instructions, generally written instructions, although electronic storage media (e.g., magnetic diskette or optical disk) containing instructions are also acceptable, relating to the use of component (s) of the methods described herein. The instructions included with the kit generally include information as to the components and their administration to an individual.V. Method of PreparationCompounds provided herein can be prepared by various synthetic processes. The choice of particular structural features and / or substituents may influence the selection of one process over another. The selection of a particular process to prepare a given compound is within the purview of the person of skill in the art. Some starting materials for preparing compounds of the present application are available from commercial chemical sources. Other starting materials, for example as described below, are readily prepared from available precursors using straightforward transformations that are well known in the art.In some embodiments, the compound of Formula (I) may be prepared all or in part using solid phase peptide synthesis (SPPS) or solution phase coupling techniques known in the art, for example, using the synthetic procedures found in Stewart and Young, 1984, Solid Phase Synthesis, Second Edition, Pierce Chemical Co., Rockford, Ill. ; Fields and Noble, 1990, “Solid phase peptide synthesis utilizing 9-fluorenylmethyloxycarbonyl amino acids, ” Int. J. Pept. Protein Res. 35: 161-214; Geysen et al., 1987, J. Immunol. Methods 102: 259-274.Accordingly, in some embodiments, in SPPS, an Nɑ -protected linker group, such as a tert-butoxycarbonyl (Boc) or 9-fluorenylmethyloxycarbonyl (Fmoc) amino acid linker group, may be activated at theα-carbonyl and coupled with the deprotected Nα functionality of the solid phase support. The newly added Nα -protected linker group may be then deprotected and coupled to the next Nα -protected linker group if necessary, until the final cleavage step. It would be appreciated by the person skilled in the art the chemistry of the coupling, deprotection, and final cleavage step of the linker from the solid phase support depends on choice ofα N-protecting group. In some embodiments, the cleavage may be accomplished by treatment with acid, for example trifluoro acetic acid (TFA) optionally in the presence of scavenger reagents such as triisopropylsilane. In some embodiments, when theα N-protecting group is Fmoc, cleavage in acid may also result in deprotection of the side chains.Therefore, in an exemplary embodiment, the compounds of Formula (I) may be prepared using fluorenylmethyloxycarbonyl (Fmoc) solidphase peptide synthesis chemistry known in the art. Accordingly, in some embodiments, the compounds of Formula (I) or fragments therefore may be prepared, manually or by using automated multiple solid-phase peptide synthesizer, using a Wang resin, Rink Amide-MBHA or equivalent resin and Fmoc-protected linker group derivatives with suitable side-chain protections such as Fmoc-Ala-OH, Fmoc-Arg (Pbf) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Asp (OtBu) -OH, Fmoc-Cys (Trt) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Gly-OH, Fmoc-His (Trt) -OH, Fmoc-Ile-OH, Fmoc-Leu-OH, Fmoc-Lys (Boc) -OH, Fmoc-Met-OH, Fmoc-Phe-OH, Fmoc-Pro-OH, Fmoc-Ser (tBu) -OH, Fmoc-Thr (tBu) -OH, Fmoc-Trp (Boc) -OH, Fmoc-Tyr (tBu) -OH, Fmoc-Val-OH, Fmoc-Lys (Mtt) -OH, Fmoc-Lys (ivDde) -OH, Fmoc-Nle-OH, Fmoc-8-amino-3, 6-dioxaoctanoic acid (Fmoc-OEG-OH) , Fmoc-Glu-OtBu. In some embodiments, the resin may be swelled using a suitable solvent such as combination of dichloromethane (DCM) and dimethylformamide (DMF) . Prior to each coupling step the base-labile Nα-protecting group Fmoc may be cleaved off from the Fmoc protected linker groups using a suitable base such as piperidine in a suitable solvent such as DMF for time to cleave to cleave the Fmoc protecting group, for example, about 10-15 min. In some embodiments, the resin may be subsequently washed with a suitable solvent such as the DMF to, for example, remove piperidine. In some embodiments, an excess amount of the Fmoc-linker group (e.g., 4 to 8 10 molar equivalent) may be subsequently coupled using coupling agents known in the art, for example, N, N’ -diisopropylcarbodiimide (DIC) and ethyl cyanohydroxyiminoacetate (Oxyma, e. g Oxyma ) or (Benzotriazo1-yloxy) tripyrrolidinophosphonium hexafluorophosphate (PyBOP) and (1-Hydroxybenzotriazole (HOBt) , in a suitable solvent such as DMF for about 1 to about 2 hours and then further washed with a suitable 15 solvent, such as DMF. The coupling step is repeated once for each linker group.In some embodiments, when necessary, the methyltrityl (Mtt) group of the Fmoc-Lys (Mtt) -OH (i.e., N-α-Fmoc-N-ε-4-methyltrityl-L-lysine) linker group or the deprotected Lys (Mtt) -residue in the linker fragment may be removed by treating the group or residue with hexafluoroisopropanol (HFIP) in a suitable solvent such as dichloromethane (DCM) (e.g. 20 about 30%v / v) for suitable amount of time, for example, about 1 hour, followed by washing the resin with the suitable solvent and repeating the treatment with HFIP in DCM with a final washing with DCM after treatment.In some embodiments, after coupling, the compound of Formula (I) , or fragment thereof may be cleaved from the solid phase by treatment with a suitable acid, for example, trifluoroacetic acid (TFA) , and optionally in the presence of a trialkylsilane such as triisopropylsilane (TIP) and water and then precipitated with a suitable solvent such as diethyl ether. The product may be dissolved in a suitable solvent such as water and acetonitrile and purified using high-performance liquid chromatography (HPLC) such as reversed phase HPLC using a suitable solvent or solvent mixture such as water with acetonitrile and TFA with an increasing gradient of acetonitrile. In some embodiments, relevant fractions may be checked by analytical UPLC. Fractions containing the pure target compounds are pooled and freeze-dried.In some embodiments, the chelating group such as DOTA may be conjugated to the linker fragment, for example, ε-amine of a lysine residue of the linker fragment or the linker fragment attached to the SSTR2 binding moiety and / or effector moiety using active ester chemistry known in the art. For example, DOTA may be combined with the linker fragment in the presence of a base such as an amine.In some embodiments, the chelating groups may be synthesized through methods known in the art or are commercially available. For example, DOTA is available from Sigma-Aldrich (St. Louis, Missouri, United States) .In some embodiments, the formation of a desired compound salt may be achieved using standard techniques. For example, the neutral compound may be treated with an acid or base in a suitable solvent and the formed salt is isolated by filtration, extraction or any other suitable method.In some embodiments, the formation of solvates may vary depending on the compound and the solvate. In general, solvates may be formed by dissolving the compound in the appropriate solvent and isolating the solvate by cooling or using an antisolvent. In some embodiments, the solvate may be dried or azeotroped under ambient conditions. In some embodiments, the selection of suitable conditions to form a particular solvate can be made by a person skilled in the art. Examples of suitable solvents are ethanol, water and the like. When water is the solvent, the molecule is referred to as a “hydrate” . The formation of solvates of the compounds of the application will vary depending on the compound and the solvate. In some embodiments, solvates may be formed by dissolving the compound in the appropriate solvent and isolating the solvate by cooling or using an antisolvent. In some embodiments, the solvate may be dried or azeotroped under ambient conditions.In some embodiments, where appropriate, suitable protecting groups may be added to, and subsequently removed from, the various reactants and intermediates in a manner that will be readily understood by one skilled in the art. Conventional procedures for using such protecting groups as well as examples of suitable protecting groups are described, for example, in “Protective Groups in Organic Synthesis” , T.W. Green, P.G.M. Wuts, Wiley-Interscience, New York, (1999) . It is also to be understood that a transformation of a group or substituent into another group or substituent by chemical manipulation can be conducted on any intermediate or final product on the synthetic path toward the final product, in which the possible type of transformation is limited only by inherent incompatibility of other functionalities carried by the molecule at that stage to the conditions or reagents employed in the transformation. Such inherent incompatibilities, and ways to circumvent them by carrying out appropriate transformations and synthetic steps in a suitable order, will be readily understood to one skilled in the art. Examples of transformations are given herein, and it is to be understood that the described transformations are not limited only to the generic groups or substituents for which the transformations are exemplified. References and descriptions of other suitable transformations are given in “Comprehensive Organic Transformations –A Guide to Functional Group Preparations” R.C. Larock, VHC Publishers, Inc. (1989) . References and descriptions of other suitable reactions are described in textbooks of organic chemistry, for example, “Advanced Organic Chemistry” , March, 4th ed. McGraw Hill (1992) or, “Organic Synthesis” , Smith, McGraw Hill, (1994) . Techniques for purification of intermediates and final products include, for example, straight and reversed phase chromatography on column or rotating plate, recrystallisation, distillation and liquid-liquid or solid-liquid extraction, which will be readily understood by one skilled in the art.EXAMPLESThe following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use the present invention, and are not intended to limit the scope of what the inventors regard as their invention nor are they intended to represent that the exemplary experiments below are all or the only experiments performed. The examples below are intended to be purely exemplary of the application and should therefore not be considered to limit the application in any way. The following examples and detailed description are offered by way of illustration and not by way of limitation.Example 1. Synthesis of Exemplary Compounds of Formula I1.1 ReagentsThe Fmoc-protected amino acid derivatives used, unless specifically stated otherwise, were the standard recommended: Fmoc-Ala-OH, Fmoc-Arg (Pbf) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Asp (OtBu) -OH, Fmoc-Cys (Trt) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Gly-OH, Fmoc-His (Trt) -OH, Fmoc-Ile-OH, Fmoc-Leu-OH, Fmoc-Lys (Boc) -OH, Fmoc-Leu-OH, Fmoc-Met-OH, Fmoc-Phe-OH, Fmoc-D-Phe-OH, Fmoc-Pro-OH, Fmoc-D-Pro-OH, Fmoc-Ser (tBu) -OH, Fmoc-Thr (tBu) -OH, Fmoc-Trp (Boc) -OH, Fmoc-D-Trp (Boc) -OH, Fmoc-Tyr (tBu) -OH, Fmoc-Val-OH, Fmoc-Lys (Mtt) -OH, Fmoc-Lys (ivDde) -OH, Fmoc-Glu-OtBu, Fmoc-Thr (tBu) -ol (CAS#189337-28-8) , Fmoc-8-amino-3, 6-dioxaoctanoic acid (Fmoc-OEG-OH) , Fmoc-8-amino-octanoic acid (Fmoc-Aoc-OH) , Fmoc-PEG1-OH (Fmoc-HN-CH2CH2O-CH2CH2CO2H) , Fmoc-PEG3-OH (Fmoc-HN- [CH2CH2O] 3-CH2CH2CO2H) , Fmoc-PEG6-OH (Fmoc-HN- [CH2CH2O] 6-CH2CH2CO2H) etc. Other reagents used included DOTA-tris (tert-butyl ester) , DOTAGA-tetra (t-Bu ester) , etc.1.2 C-terminal acid peptidesThe C-terminal acid peptides were prepared using Wang resin. The coupling of the first C-terminal residue started with swelling Wang resin (loading 1.1 mmol / g, 5.0 mmol) in DCM (50 mL) in a SPPS reaction vessel with N2 bubbling for 30 min. The resin was then drained and washed with DMF (50 mL) 3 times. In a separate flask, a mixture of Fmoc-Thr (tBu) -OH (15 mmol) , DIC (15 mmol) and 4-dimethylaminopyridine (DMAP) (0.5 mmol) in DMF (60 mL) was stirred for 15 min at room temperature before being transferred to the above reaction vessel. The resulting mixture was bubbled with N2 for 4 h, then drained and washed with DMF (50 mL) 6 times, followed by the addition of DMF (60 mL) , acetic anhydride (50 mmol) and DMAP (0.50 mmol) . The resulting mixture was bubbled with N2 for 2 h, then drained and the resin was washed with DMF (50 mL) 6 times.1.3 C-terminal amide peptidesThe C-terminal amide peptides were prepared using Rink Amide-MBHA resin. The first C-terminal residue (Fmoc-Thr (tBu) -OH) was attached following a standard amide bond coupling conditions using PyBOP / HOBt / DIEA as coupling reagents. The resin was washed with DMF 6 times before the coupling of the second residue.1.4 C-terminal alcohol peptidesThe C-terminal alcohol peptides were prepared using Chlorotrityl Chloride (CTC) resin, and the first C-terminal residue, Fmoc-Thr (tBu) -ol, was attached to CTC resin by mixing 2 eq. of Fmoc-Thr (tBu) -ol with the resin in the presence of 3 eq. of DIEA in DMF at room temperature for 4 h, followed by washing and blocking with 50%MeOH / DMF at. room temperature for 1 h. The resin was then washed with DMF 6 times.1.5 Standard Solid-Phase Assembly protocolThe synthesis was performed using Fmoc-based chemistry manually. The stepwise assembly was conducted following the below steps:1) Pre-swelling the resin with DCM and DMF;2) Removing the Fmoc group by 20%piperidine; 2 treatments, 10 min each;3) Washing the resin with DMF to remove piperidine;4) Adding Fmoc-amino acid (1 mmol) , PyBOP (1 mmol) , HOBt (0.2 mmol) and DMF (5 mL) to a reaction vessel containing 0.20 mmol resin followed by addition of DIEA (2 mmol) , the resulting mixture was mixed by bubbling nitrogen for 1 –2 h;5) Draining the resin, and washed the resin with DMF 6 times6) When needed, the N-epsilon-lysine Mtt protective group could be removed by treating the resin with 30% (v / v) HFIP in DCM for 1 h twice; drained the resin and washed it with DCM and DMF;7) The final wash before resin cleavage was done with DMF (3 times) , DCM (3 times) and MeOH (3 times) , respectively.1.6 Resin cleavage and disulfide bridge forming conditions and purificationAfter solid-phase peptide assembly was completed, the resin was subject to a 1.5 –3 h treatment of TFA / triisopropylsilane (TIS) / H2O (95: 2.5: 2.5, v / v / v) . The resin was filtered off and washed one time with TFA, the combined filtrate was treated with methyl tert-butyl ether (MTBE) to precipitate the crude peptide out of the solution. The precipitate was collected by centrifugation and washed 3 times with diethyl ether, briefly dried, then re-dissolved in acetonitrile (ACN) and H2O to a concentration of 1 mM or lower. The volume ratio of ACN to H2O could be adjusted to a relatively low percentage of ACN while ensuring a completely clear solution could be achieved. The pH of the resulting solution was adjusted to 4-5 by the addition of acetic acid, then a solution of iodine in methanol (1.0 gram iodine in 100 mL methanol) was added dropwise until the iodine purple color stayed. The slightly purple mixture was then gently stirred for another 30 min before the addition of ascorbic acid solid (afew mg each portion) until the purple color completely disappeared. The resulting crude product was subjected to purification by using a reverse phase preparative HPLC system (Waters Delta Prep 4000) with a C18-reverse phase column. Mobile phases: A: 0.1%TFA / H2O; B: 0.1%TFA / ACN. Relevant fractions were analyzed by analytical ultra-performance liquid chromatography (UPLC) . The pure fractions were pooled and freeze-dried affording the product as a white lyophilized powder.1.7 LC-MS conditionInstrument: Agilent prime-6125B_2LCMSColumn: Boltimate EXT C18 CoreShell 4.6 x 50 mm, 2.7 μmDetection: UV (254 nm 214 nm 280 nm) and MS (ESI, 100 to 2000 amu) Mobile Phase: A: H2O (0.05%formic acid) ; B: ACN (0.05%formic acid) Flow Rate: 2.0 mL / minColumn Temperature: 45℃Gradient: 10 %to 95%B within 1.5 min, followed by 95%B for 1.0 min1.8 Analytical HPLC conditionInstrument: WATERS ARC UPLCColumn: XBridge BEH peptide BEH C18, 3.5 μm, 2.1 mm x 150 mmDetection: UV 254 nm, 214 nm, 280 nmMobile Phase: A: H2O (0.1%TFA) ; B: ACN (0.1%TFA)Column Temperature: 40℃Flow Rate: 0.6 mL / minGradient:1.9 Radiochemistry methodsFour μL reference compound or the exemplary compound of the present application in DMSO stock solution (2000 μM) was added to a 0.5 M NaOAc buffer (20-50 μL, pH = 4.5) , followed by supplement of 2 mCi 177Lu (ITM Isotope Technologies Munich) . The resulting mixture was heated to 95℃ for 15 min and then analyzed by radio-TLC and radio-HPLC (column: Shim-pack GIST 5μm 4.6x150mm; buffer A: 0.2%formic acid H2O; buffer B: 0.1%formic acid acetonitrile; flow rate: 1 mL / min; gradient: 0-5 min: 10%B to 95%B; then 5-8 min: 95%B) . The radionuclide labeled compound was used immediately or diluted by a PBS buffer containing freshly added 3 mg / mL ascorbate.1.10 Synthesis of Exemplary Compounds of Formula (I)The following exemplary compounds of Formula (I) were prepared using the above methods, and further characterized by LC-MS, as shown in Table 2.Table 2. Synthesis and characterization of the exemplary compounds of the present application.Abbreviations:T: Threonine; C: Cysteine; K: Lysine; k: D-Lysine; w: D-Tryptophan; Y: Tyrosine; f: D-Phenylalanine; A: Alanine; G: Glycine; W: Tryptophan; Nle: Non-leucine; D: Aspartic acid; S: Serine; p: D-proline; R: Arginine:gE: gamma-Glutamic acid; eK: epsilon-Lysine-OH: C-terminal acid; -NH2: C-terminal amide; Thr (ol) : C-terminal alcohol[CXXXXC] : Disulfide bondDOTA: 1, 4, 7, 10-Tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid;DOTAGA: 2- [1, 4, 7, 10-Tetraazacyclododecane-4, 7, 10-trisacetic acid] -pentanedioic acidOEG: H2N- [CH2CH2O] 2-CH2CO2HExample 2. Binding Affinities and Binding Selectivity of the Exemplary CompoundsHEK 293T cells were transfected with SSTR2-expressing plasmid by Lipofectamine 2000 reagent. 24 hours after transfection, cells were harvested and suspended with assay buffer (1%OVA in DMEM) . Then cells were seeded into 96-well plate with Cy5-labled DOTATATE (Seq: Cy5-OEG-Lys (DOTA) -f [CYwKTC] T-OH) as the competitive ligand. The testing compound was further added into the wells at different concentrations. After incubation for 1 hour at dark, cells were washed and suspended in FACS buffer (1%OVA in DPBS) . The fluorescent signal was detected by flow cytometry and the binding affinity of the testing compound was evaluated by calculation of IC50 for competitive binding of the testing compound with the competitive ligand.As shown in Table 3, the exemplary compounds of the present application all displayed specific binding to SSTR2, with an IC50 value in the range of about 0.1 nM to about 10 nM in the assay as described above, in which:Category A stands for value of Reference’s IC50 / Exemplary Compound’s IC50 being less than 1.0,Category B stands for value of Reference’s IC50 / Exemplary Compound’s IC50 between 1.0 and 2.0,Category C stands for value of Reference’s IC50 / Exemplary Compound’s IC50 between 2.0 and 4.0,CategoryD stands for value of Reference’s IC50 / Exemplary Compound’s IC50 between 4.0 and 8.0, andCategory E stands for value of Reference’s IC50 / Exemplary Compound’s IC50≥ 8.0.Table 3. Binding affinities of the exemplary compounds of the present applicationAbbreviations:T: Threonine; C: Cysteine; K: Lysine; k: D-Lysine; w: D-Tryptophan; Y: Tyrosine; f: D-Phenylalanine; A: Alanine; G: Glycine; W: Tryptophan; Nle: Non-leucine; D: Aspartic acid; S: Serine; p: D-proline; R: Arginine:gE: gamma-Glutamic acid; eK: epsilon-Lysine-OH: C-terminal acid; -NH2: C-terminal amide; Thr (ol) : C-terminal alcohol[CXXXXC] : Disulfide bondDOTA: 1, 4, 7, 10-Tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid;DOTAGA: 2- [1, 4, 7, 10-Tetraazacyclododecane-4, 7, 10-trisacetic acid] -pentanedioic acidOEG: H2N- [CH2CH2O] 2-CH2CO2HBased on Table 3, it was surprisingly found that compounds with fatty acid moiety A conjugated to the alpha (α) amino group of the trivalent group such as the alpha (α) amino group of Lys or D-Lys resulted in higher binding affinities as compared to the exemplary compounds with A conjugated to the epsilon (ε) amino group, as exemplarily shown in Table 4.Table 4 Binding affinities of the representative compounds of the present applicationIn addition, the compounds comprising an A as being a fatty monoacid moiety displayed higher binding affinities as compared to those compounds comprising an A as being a di fatty acid moiety with the same length of carbon chain, as shown in Table 5.Table 5 Binding affinities of the representative compounds of the present applicationFurthermore, the compounds comprising a fatty acid moiety containing 12-16 carbons showed more robust binding against the target, as seen in Table 6.Table 6 Binding affinities of the representative compounds of the present applicationCompound 027 were further labeled with 175Lu and 139La to evaluate the impacts of metals on binding affinities after metal chelation. Briefly, for the 175Lu labelling, LuCl3.6H2O (10.5 mg, 0.035 mmol) was added to a solution of Compound 027 (15 mg, 0.007 mmol) in 15 mL of 0.5M NaOAc buffer (pH=4.5) . The mixture was stirred at 55℃ for 30 min, followed by LCMS to confirm the completion of the reaction (MW 2319.4; 1159.8 (M+2H+) , 773.9 (M+3H+) from LCMS) . After cooling down, the reaction mixture was purified by prep-HPLC, and 11.5 mg of 175Lu-labeled compound as a white powder (purity >99%) was obtained.For 139La labelling, LaCl3.6H2O (12.4 mg, 0.035 mmol) was added to a solution of Compound 027 (15 mg, 0.007 mmol) in 15 mL of 0.5M NaOAc buffer (pH=4.5) . The mixture was stirred at 55℃ for 30 min, followed by LCMS to confirm the completion of the reaction (MW 2283.3; 1142.2 (M+2H+) , 761.8 (M+3H+) , 571.7 (M+4H+) from LCMS) . After cooling down, the reaction mixture was purified by prep-HPLC, and 6.9 mg of the 139La-labeled compound as a white powder (purity >99%) was obtained.The binding affinities of the 175Lu and 139La labeled Compound 027 were further analyzed by using the same method as described above in Example 2. As shown in Table 7, after chelation with 175Lu or 139La , Compound displayed comparable binding affinities to the non-labeled compound.Table 7 Binding affinities of the metal-labeled compoundsTo analyze the binding selectivity of the compounds, HEK 293T cells were transfected with plasmid expressing SSTR1, 2, 3, 4, or 5 by Lipofectamine 2000 reagent. 24 hours after transfection, cells were harvested and suspended with assay buffer (1%OVA in DMEM) . Then cells were seeded into 96-well plate with Cy5-labled Somatostatin peptide SST-14 (Seq: Cy5-OEG-OEG-Ala-Gly- [Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys] -OH) as the competitive ligand. Then the Compound 027 was further added into the wells at different concentrations. After incubation for 1 hour at dark, cells were washed and suspended in FACS buffer (1%OVA in DPBS) . The fluorescent signal was detected by flow cytometry and the binding affinities of the Compound 027 was evaluated by calculation of IC50 for competitive binding of the testing compound with the competitive ligand. As shown in Table 8, the Compound 027 displayed >500-fold selectivity against SSTR1, 3, 4 and 5 as compared to SSTR2.Table 8 Binding Selectivity of the CompoundTo analyze the cross reactivity of the compounds with SSTR2, HEK 293T cells were transfected with plasmid expressing SSTR2 from human, mouse, rat or dog by Lipofectamine 2000 reagent. 24 hours after transfection, cells were harvested and suspended with assay buffer (1%OVA in DMEM) . The cells were seeded into 96-well plate with Cy5-labled DOTATATE (Seq: Cy5-OEG-Lys (DOTA) -f [CYwKTC] T-OH) as the competitive ligand. Then the Compound 027 was added into the wells at different concentrations. After incubation for 1 hour at dark, cells were washed and suspended in FACS buffer (1%OVA in DPBS) . The fluorescent signal was detected by flow cytometry and the binding affinities of the Compound 027 was evaluated by calculation of IC50 for competitive binding of the testing compound with the competitive ligand. As shown in Table 9, the Compound 027 demonstrated comparable binding affinity against SSTR2 from human, mouse, rat and dog.Table 9 Cross Reactivity of the Compound in Different SpeciesExample 3. Biodistribution Study of177Lu labeled compoundsAll animal care and experimental procedure were performed by following the animal protocols approved by the ethics committees of Kyinno Biotechnology and China Institute of Radiation Protection. The NOD SCID mice (Kyinno Biotechnology, Beijing) were utilized for these studies. Mice were kept at below 5 per cage in sterile, microisolator cages under temperature-and humidity-controlled conditions with a 12 h light / 12 h dark schedule and were fed irradiated rodent chow and reverse osmosis (RO) sterile water ad libitum. In preparation for tumor cell inoculations, mice were anesthetized with isoflurane (RWD Life Science Inc. ) at an induction rate of 4%and were maintained at a rate of 2.5%with 0.4 L oxygen delivered via precision vaporizer and a non-rebreathing apparatus. The mice received subcutaneous rear flank injections of approximately 4 × 106 AR42J (human pancreatic cancer cell line) or H524 (human small cell lung cancer cell line) cells suspended in 200μL of phosphate-buffered saline (PBS) and Matrigel (Corning) (1 / 1) . Xenografted tumors were allowed to grow for~2-4 weeks post-inoculation till the average tumor size to ~200 mm3.Each 177Lu labeled compound in 100μL of 0.9%NaCl was then administrated to the mice by the tail vein injection at a dose of~10 –50μCi (~0.37 –1.85 MBq) with specific activity of 50-1000 μCi / nmol. After administration, the mice were euthanized at different time points including1, 4, 24, 72 and 168h, and then tissues and organs were excised from the animals. The tissues and organs were weighed, counted in a PerkinElmer 2480 WIZARD2γ counter, and the percent injected dose (%ID) and %ID / g of each organ or tissue were calculated.As shown inTable 9-10 andFIG. 1, all tested compounds displayed high level of uptake of the radionuclide in tumor meanwhile acceptable uptake in normal tissues, including blood, kidney and liver. Surprisingly, it was found that the chemical structure and net charge of the linkers LZ and LA of the exemplary compounds had significant impacts on their in vivo biodistribution. For example, Compound027 with an amino acid linker -Asp-Asp-as LA and -Gly-Gly-Gly-as LZ displayed higher tumor uptake, as well as higher T / K, and T / B as compared to the reference compound, indicating its superior efficacy as well as an improved safety profile.The biodistribution of 177Lu labeled Compound 027 versus 177Lu labeled Reference Compound in AR42J tumor-bearing mice at different time points were further evaluated. As shown in Table 11 and FIG. 2A and FIG. 2B, after administration of177Lu labeled Compound 027, high tumor uptake was observed at 1 h with a value of 56.32 %ID / g and peaked at 24 h with a value of 102.65 %ID / g. Durable tumor uptake was identified with a decrease to 59.65 %ID / g and 40.25 %ID / g at 72 h and 168 h, respectively. The highest non-tumor uptake was observed at early timepoints in pancreas, kidney and blood but quickly cleared to a low or undetectable level at 168 h.The area under the plasma drug concentration-time curve (AUC) reflecting actual body exposure to the drug as well as the tumor-to-organ AUC ratios of177Lu labeled Compound 027 in AR42J xenograft model were further calculated and summarized in Table 12.Table 11. Biodistribution of177Lu labeled Compound 027 in AR42J tumor-bearing mice (n=3 / timepoint)Table 12. Mean AUC (area under the curve) and AUC ratio (tumor / organ)In addition, the biodistribution of 177Lu labeled Compound 027 versus 177Lu labeled Reference Compound in H524 tumor-bearing mice at different time points were evaluated. As shown inTable 13 andFIG. 3A and FIG. 3B, high tumor uptake was observed at 1 h with a value of 29.41 %ID / g and peaked at 4 h with a value of 46.98 %ID / g. Durable tumor uptake was identified with a decrease to 39.18 %ID / g, 12.83 %ID / g and2.95 %ID / g at 24 h, 72 h and 168 h respectively. The highest non-tumor uptake was observed at early timepoints in pancreas, kidney and blood but quickly cleared to a low or undetectable level at 168 h.The area under the plasma drug concentration-time curve (AUC) reflecting actual body exposure to the drug as well as the tumor-to-organ AUC ratios of177Lu labeled Compound 027 in H524 xenograft model were further calculated and summarized in Table 14.Table 13. Biodistribution of 177Lu labeled Compound 027 in H524 tumor-bearing mice (n=3 / timepoint)Table 14. Mean AUC (area under the curve) and AUC ratio (tumor / organ)Example 4 SPECT / CT imaging study of177Lu labeled compoundsAR42J tumor-bearing mice were IV-injected with about 300 μCi of exemplary 177Lu-labeled compound, with (FIG. 4B) or without (FIG. 4A) 1000-fold extra amount of non-labeled DOTATATE. 4 hours later, mice were anesthetized under 2 %isoflurane / oxygen gas and placed on the scanner. SPECT / CT images were acquired in three bed positions for 30 min using a MILabs SPECT scanner.FIG. 4A and FIG. 4B demonstrate the high and specific tumor uptake of177Lu labeled Compound 027 in a SSTR2-dependent manner.Example 5 In vivo Efficacy Studies of177Lu labeled compounds5.1 In vivo efficacy studies 177Lu labeled Compound 027 in SSTR2-expressing AR42J rat pancreatic cancer cell xenograft modelFemale Balb / c nude mice bearing SSTR2-expressing AR42J tumors were administrated with Vehicle, 177Lu-DOTATATE (18.5 MBq or 37 MBq / mouse, 18.5 MBq / nmol) or 177Lu labeled Compound 027 (18.5 MBq or 37 MBq / mouse, 18.5 MBq / nmol) via single dose tail vein injection (N=4-5 / group) . The tumor volume was measured twice per week for efficacy evaluation. Tolerability was assessed twice per week via body weight measurement.Tumor growth inhibition (TGI) was calculated as follows:TGI %= 100%× [1- (tvt (t) -tvinitial (t) ) / (tvt (v) -tvinitial (v) ) ] ,wheretvt (t) was the mean tumor volume of a treatment group on testing day,tvinitial (t) was the mean tumor volume of a treatment group on the initial day, tvt (v) was the mean tumor volume of the vehicle group on the testing day, and tvinitial (v) was the mean tumor volume of the vehicle group on the initial day.On Day 12 when the mean tumor volume (TV) of the Vehicle group reached 2, 041 mm3, significant anti-tumor activities were observed for all treatment groups (p<0.0001, One-way ANOVA with Tukey’s multiple comparison test) . The mean TVs of177Lu labeled Compound 027 at 18.5 MBq and 37 MBq were 115 mm3 and 85 mm3, with tumor growth inhibition (TGI) values of 99%and 100% (FIG. 5A) , respectively. Tumor regression was observed in 2 / 5 and 4 / 5 mice of 177Lu labeled Compound 027 at 18.5 MBq and 37 MBq respectively.The mean TVs of177Lu-DOTATATE at 18.5 MBq and 37 MBq were 120 mm3 and 131 mm3, with TGI values of 98%and 98%respectively (FIG. 5A) . Tumor regression was only observed in 1 / 5177Lu-DOTATATE at 37 MBq.On Day 24 when no mouse from treatment groups was taken down due to TV, the mean TVs of 177Lu labeled Compound 027 at 18.5 MBq and 37 MBq were 100 mm3 and 58 mm3 respectively (Figure 5A) . Tumor regression was observed in 2 / 5 and 4 / 5 mice of 177Lu labeled Compound 027 at 18.5 MBq and 37 MBq respectively. Especially, >30%tumor shrinkage was observed in 4 / 5 mice of177Lu labeled Compound 027 at 37 MBq.The mean TVs of 177Lu-DOTATATE at 18.5 MBq and 37 MBq were 1, 181 mm3 and 1,033 mm3 respectively (FIG. 5A) . No tumor regression was observed for 177Lu-DOTATATE treatment groups.Compared with 177Lu-DOTATATE, 177Lu labeled Compound 027 treatments exhibited significantly better efficacy at the same dose levels (p<0.01, One-way ANOVA with Tukey’s multiple comparison test) .The Best of Response (BOR) for 177Lu labeled Compound 027 treatment occurred on Day 20 when 30%tumor shrinkage was observed in 2 / 5 and 4 / 5 mice of177Lu labeled Compound 027 at 18.5 MBq and 37 MBq respectively. Especially, complete tumor regression was observed in 1 / 5 mice of177Lu labeled Compound 027 at 37 MBq. On the same day, tumor regression was only observed in 1 / 5 mice of177Lu-DOTATATE at 37 MBq.No obvious weight loss was observed during the study for all mice (FIG. 5B) .5.2 In vivo efficacy studies of 177Lu-DOTATATE and 177Lu labeled Compound 027 after initial treatment of 177Lu-DOTATATE in SSTR2-expressing AR42J rat pancreatic cancer cell xenograft modelFemale Balb / c nude mice bearing SSTR2-expressing AR42J tumors were administrated by Vehicle (N=5) or 177Lu-DOTATATE (18.5 MBq / mouse, 18.5 MBq / nmol, N=15) via single dose tail vein injection. After the mean TV of 177Lu-DOTATATE group reached to >3-fold increase compared with that of the initial day, 10 mice were selected and randomized into two groups (N=5) for the treatments of 177Lu-DOTATATE (18.5 MBq / mouse, 18.5 MBq / nmol) or 177Lu labeled Compound 027 (18.5 MBq / mouse, 18.5 MBq / nmol) . The efficacy was evaluated with tumor volume measurement twice per week. Tolerability was assessed via body weight measurements twice per week.On Day 17 when the mean tumor volume (TV) of the Vehicle group reached 2, 206 mm3, significant anti-tumor activities were observed for 177Lu-DOTATATE (p<0.0001, One-way ANOVA with Tukey’s multiple comparison test) . The mean TV of 177Lu-DOTATATE at 18.5 MBq was 146 mm3, with tumor growth inhibition (TGI) value of 97% (FIG. 6A) . One mouse from 177Lu-DOTATATE group died on Day 17 without specific findings via gross anatomy.On Day 19 when the mean TV of 177Lu-DOTATATE at 18.5 MBq reached to >3-fold increase compared with that of the initial day (391 mm3 vs 92 mm3) , 10 mice were selected and randomized into two groups for the treatments of 18.5 MBq 177Lu-DOTATATE or 177Lu labeled Compound 027, respectively.On Day 38 when the TV of one mouse in 177Lu-DOTATATE retreatment group reached over 2,000 mm3, the mean TVs of 177Lu-DOTATATE and 177Lu labeled Compound 027 retreatment groups were 1,379 mm3 and 284 mm3 respectively. 177Lu labeled Compound 027 retreatment exhibited significantly better efficacy than 177Lu-DOTATATE retreatment (p<0.01, Student t test) . Compared with that of Day 19, tumor regression was observed in 2 / 5 mice of177Lu labeled Compound 027 retreatment on Day 38 while no tumor regression was observed in mice of 177Lu-DOTATATE retreatment (FIG. 6A) .No obvious weight loss was observed during the study for all mice except one mouse in 177Lu-DOTATATE retreatment group shown >15%body weight loss through Day 31 to Day 38 (FIG. 6B and FIG. 6C) .5.3 In vivo efficacy studies of177Lu-DOTATATE and 177Lu labeled Compound 027 evaluated in SSTR2-expressing H524 human lung cancer cell xenograft model (medium SSTR2 expression)Female Balb / c nude mice bearing SSTR2-expressing H524 tumors were administrated with Vehicle, 177Lu-DOTATATE (18.5 MBq or 37 MBq / mouse, 18.5 MBq / nmol) or 177Lu labeled Compound 027 (18.5 MBq or 37 MBq / mouse, 18.5 MBq / nmol) via single dose tail vein injection (N=5 / group) . The efficacy was evaluated with tumor volume measurement twice per week. Tolerability was assessed via body weight measurements twice per week.On Day 24 when the mean tumor volume of the Vehicle group reached 1, 630 mm3, significant anti-tumor activities were observed for all treatment groups (p<0.0001, One-way ANOVA with Tukey’s multiple comparison test) . The mean TVs of177Lu labeled Compound 027 at 18.5 MBq and 37 MBq were 0 mm3 and 1 mm3 respectively, with tumor growth inhibition (TGI) values of 106%and 106% (FIG. 7A) . Tumor regression was observed in 5 / 5 and 5 / 5 mice of177Lu labeled Compound 027 at 18.5 MBq and 37 MBq respectively. Especially, complete tumor regression was observed in 5 / 5 and 4 / 5 mice of177Lu labeled Compound 027 at 18.5 MBq and 37 MBq respectively. The mean TVs of177Lu-DOTATATE at 18.5 MBq and 37 MBq were 447 mm3 and 205 mm3 respectively, with TGI values of 77%and 93%respectively (FIG. 7A) . Tumor regression was only observed in 1 / 5177Lu-DOTATATE at 37 MBq, which was also reached to complete tumor regression.The Best of Response (BOR) for 177Lu labeled Compound 027 treatment occurred on Day 20 when complete tumor regression was observed in 5 / 5 and 5 / 5 mice of 177Lu labeled Compound 027 at 18.5 MBq and 37 MBq respectively. On the same day, tumor regression was only observed in 2 / 5 mice of177Lu-DOTATATE at 37 MBq, with one of them showing complete tumor regression.No obvious weight loss was observed during the study for all mice except for one mouse in 177Lu labeled Compound 027 18.5 MBq group shown >10%body weight loss on Day 24 (FIG. 7B) .5.4 In vivo efficacy studies of177Lu-DOTATATE and 177Lu labeledCompound 027 evaluated in SSTR2-expressing H69 human lung cancer cell xenograft model (low SSTR2 expression)Female Balb / c nude mice bearing SSTR2-expressing H69 tumors were administrated by Vehicle, 177Lu-DOTATATE (18.5 MBq or 37 MBq / mouse, 18.5 MBq / nmol) or 177Lu labeled Compound 027 (18.5 MBq or 37 MBq / mouse, 18.5 MBq / nmol) via single dose tail vein injection (N=5 / group) . The efficacy was evaluated with tumor volume measurement twice per week. Tolerability was assessed via body weight measurements twice per week.On Day 27 when the mean tumor volume of the Vehicle group reached 1, 098 mm3, significant anti-tumor activities were observed for all treatment groups (p<0.05 for 177Lu-DOTATATE at 18.5 MBq and 37 MBq, p<0.001 for 177Lu labeled Compound 027 at 18.5 MBq and p<0.0001 for 177Lu labeled Compound 027 at 37 MBq, One-way ANOVA with Tukey’s multiple comparison test) . The mean TVs of 177Lu labeled Compound 027 at 18.5 MBq and 37 MBq were 528 mm3 and 248 mm3 respectively, with tumor growth inhibition (TGI) values of 56%and 84% (FIG. 8A) . Complete tumor regression was observed in 1 / 5 mice of 177Lu labeled Compound 027 at 37 MBq. The mean TVs of177Lu-DOTATATE at 18.5 MBq and 37 MBq were 711 mm3 and 686 mm3 respectively, with TGI values of 38%and 41%respectively (FIG. 8A) . 177Lu labeled Compound 027 showed significantly better efficacy than 177Lu-DOTATATE at 37 MBq level when comparing the tumor volumes (p<0.05, One-way ANOVA with Tukey’s multiple comparison test) .The Best of Response (BOR) for 177Lu labeled Compound 027 treatment occurred on Day 16 when 30%tumor shrinkage was observed in 4 / 5 mice of177Lu labeled Compound 027 37 MBq, with one of them showing complete tumor regression. On the same day, no tumor regression was observed in other groups.No obvious weight loss was observed during the study for 177Lu labeled Compound 027 treatment groups and 177Lu-DOTATATE 37 MBq group. Three mice of177Lu-DOTATATE 18.5 MBq group shown temporarily >10%body weight loss on Day 16 while recovered since Day 20. One mouse of177Lu-DOTATATE 18.5 MBq group died on Day 27 without specific findings via gross anatomy (FIG. 8B) .In summary, the test article 177Lu labeled Compound 027 showed obvious anti-tumor efficacy in different SSTR2-expressing xenograft models at both 18.5 MBq and 37 MBq levels. Better efficacy was observed by 177Lu labeled Compound 027 compared with 177Lu-DOTATATE at the same dose levels. Especially, when tumor progressed after the initial treatment of 177Lu-DOTATATE in SSTR2-expressing AR42J models, re-treatment of177Lu labeled Compound 027 exhibited significantly stronger anti-tumor activity than re-treatment of177Lu-DOTATATE at the same dose level with tumor regression observed. Mice were tolerated well without obvious body weight loss after receiving 177Lu labeled Compound 027 treatment at 18.5 MBq and 38 MBq levels.Example 6 Biodistribution Study of225Ac labeled compoundsThe biodistribution of225Ac labeled Compound 027 in AR42J tumor-bearing mice at different time points were further evaluated. As shown inTable 15 andFIG. 9, after administration of 225Ac labeled Compound 027, high tumor uptake was achieved within 4 h at a value of 55.87 %ID / g, followed by durable tumor retention at a value of 51.77 %ID / g and 53.89 %ID / g at 24 h and 72 h, respectively. For non-tumor organs, relatively high uptake was observed in pancreas, kidney and stomach at 4h, but quickly cleared to lower levels after 24h.Table 15 Biodistribution in NET AR42J xenograft model (n=5 / timepoint)Example 7 In vivo Efficacy Studies of225Ac labeled compoundsIn vivo efficacy of225Ac labeled Compound 027 was evaluated in SSTR2-expressing AR42J rat pancreatic cancer cell xenograft model. Briefly, Female Balb / c nude mice bearing SSTR2-expressing AR42J tumors were administrated with Vehicle or 225Ac labeled Compound 027 (18.5 kBq or 37 kBq / mouse, 185 kBq / nmol) via single dose tail vein injection (N=5 / group) . The tumor volume was measured twice per week for efficacy evaluation. Tolerability was assessed twice per week via body weight measurement.On Day 14 when the mean tumor volume (TV) of the Vehicle group reached 1, 359 mm3, significant anti-tumor activities were observed for 225Ac-Compound 027 treatment groups (p<0.0001, One-way ANOVA with Tukey’s multiple comparison test) . The mean TVs of225Ac labeled Compound 027 at 18.5 kBq and 37 kBq were 15 mm3 and 7 mm3, with tumor growth inhibition (TGI) values of 106%and 106% (FIG. 10A) , respectively. Tumor regression was observed in all mice of225Ac labeled Compound 027 at 18.5 kBq and 37 kBq.The Best of Response (BOR) for 225Ac labeled Compound 027 treatment occurred on Day 28 when 30%tumor shrinkage was observed in all mice of225Ac labeled Compound 027 at 18.5 kBq and 37 kBq. Furthermore, complete tumor regression was observed in 4 / 5 and 3 / 5 mice of225Ac labeled Compound 027 at 18.5 kBq and 37 kBq, respectively.No obvious weight loss was observed during the study for all mice (FIG. 10B) , indicating safety of the administration of the 225Ac labeled Compound.Example 8 PET / CT imaging study of68Ga labeled compoundsSCLC-21H tumor-bearing mice were IV-injected with about 100 μCi of 68Ga-labeled Compound 027.20 mins (0.33 hours) later, the mice were anesthetized under 2 %isoflurane / oxygen gas and placed on the scanner. PET / CT images were acquired at 0.33H, 1H and 3H post injection, respectively.As shown in FIG. 11, administration of the 68Ga labeled Compound 027 results in fast and specific tumor uptake and quick normal tissue clearance of the radioisotope within 3 hours, demonstrating promising potential of the compound for diagnosis purposes.
Claims
1.A compound of formula (I) , or a pharmaceutically acceptable salt thereof: wherein:T is a trivalent moiety,Z is a somatostatin receptor 2 (SSTR2) binding moiety, wherein Z is conjugated to T via a linker LZ,E is an effector moiety, wherein E is conjugated to T via a linker LE,A is an unsubstituted or substituted fatty acid moiety, wherein A is conjugated to T via a linker LA, andLZ, LE, and LA are each independently a bond or a divalent linker.2.The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein LA is a bond or a divalent linker: – (Y) n-,wherein:n is an integer of 1-20, andeach Y is independently selected from the group consisting of an amino acid residue and -N (RN) (C2alkyleneYa) y1YbC (O) -, wherein RN is H or C1-C6 alkyl, wherein Ya is -O-, -S-, -NH-, or -N (C1-C6 alkyl) -, wherein y1 is an integer from 1 to 10, and wherein Yb is C1-C3 alkylene.3.The compound of claim 1 or claim 2, or a pharmaceutically acceptable salt thereof, wherein LA comprises one or more amino acid residues.4.The compound of any one of claims 1-3, or a pharmaceutically acceptable salt thereof, wherein LA comprises one or more amino acid residues, each independently selected from the group consisting of alanine (Ala, A) , asparagine (Asn, N) , aspartic acid (Asp, D) , glutamine (Gln, Q) , glutamic acid (Glu, E) , γGlu, glutamine (Gln) , glycine (Gly, G) , isoleucine (Ile, I) , leucine (Leu, L) , εLys, methionine (Met, M) , phenylalanine (Phe, F) , proline (Pro, P) , serine (Ser, S) , threonine (Thr, T) , tryptophan (Trp, W) , tyrosine (Tyr, Y) , valine (Val, V) , pyrrolysine (Pyl, O) , pyrroline-carboxy-lysine (PCL) , gamma-carboxyglutamic acid (Gla) , NR5C5alkyleneC (O) (Ahx) , Cysteic acid (Cya) , norleucine (Nle) , norvaline (Nva) , 2-aminooctanoic acid (Aoc) , 2-naphthylalanine (2-Nal) , 3- (trifluoromethyl) phenylalanine (TFP) , homophenylalanine (hPhe) , cyclohexylalanine (Cha) , 1-naphthylalanine (1-Nal) , 4-benzoyl-L-phenylalanine (Bpa) , 2-methoxy-4-vinylphenylalanine (MvF) , 4-fluorophenylalanine (4-F-Phe) , 4-phenyl-2, 3-dihydroxy-6-nitrophenylalanine (pNIPA) , 2- (2-naphthyl) alanine (2-Nal-ala) , 4- (4-propoxyphenyl) alanine (Ppa) , 4-carboxyphenylalanine (4-CPA) , 4-butylphenylalanine (Bua) , 2-nitrophenylalanine (2-Npa) , 4-azidophenylalanine (4-AzF) , 2- (4-nitrophenyl) ethylalanine (2-Npe) , 3-iodo-L-tyrosine (Ity) , 5, 5, 5-trifluoroleucine (TFL) , or a D enantiomer thereof.5.The compound of any one of claims 1-4, or a pharmaceutically acceptable salt thereof, wherein LA comprises one or more negatively charged amino acid residues, wherein each of the negatively charged amino acid residues is independently and optionally selected from the group consisting of D-Asp, Asp, D-Glu, Glu, D-γGlu, γGlu, and Cya.6.The compound of any one of claims 1-5, or a pharmaceutically acceptable salt thereof, wherein LA comprises one or more D-Asp, Asp, or any combination thereof.7.The compound of any one of claims 1-6, or a pharmaceutically acceptable salt thereof, wherein LA comprises one or more neutral amino acid residues, wherein each amino acid residue is independently and optionally selected from the group consisting of Gly, D-Pro, Pro, D-Ser and Ser.8.The compound of any one of claims 1-7, or a pharmaceutically acceptable salt thereof, wherein LA comprises one or more neutral amino acid residues, wherein each amino acid residue is independently and optionally selected from the group consisting of Gly, and Ser.9.The compound of any one of claims 1-8, or a pharmaceutically acceptable salt thereof, wherein LAcomprises -N (RN) (C2alkylene-O) y1YbC (O) -, wherein RN is H, y1 is an integer from 1 to 10, and Yb is C1-C3 alkylene.10.The compound of claim 9, or a pharmaceutically acceptable salt thereof, wherein the -N (RN) (C2alkyleneYa) y1YbC (O) -is -NH (C2alkyleneO) 2C1alkyleneC (O) (OEG) , -NH (C2alkyleneO) C2alkyleneC (O) (PEG1) , -NH (C2alkyleneO) 3C2alkyleneC (O) (PEG3) , or -NH (C2alkyleneO) 6C2alkyleneC (O) (PEG6) .11.The compound of any one of claims 2-10, or a pharmaceutically acceptable salt thereof, wherein n is an integer of 1-15, and each Y is independently selected from the group consisting of: Ahx, Cya, Gla, Gly, D-Ala, Ala, D-Val, Val, D-Leu, Leu, D-Phe, Phe, D-Pro, Pro, D-Met, Met, D-Trp, Trp, D-Thr, Thr, D-Tyr, Tyr, D-Nle, Nle, D-Ser, Ser, D-Asp, Asp, D-Glu, Glu, D-γGlu, γGlu, OEG and PEG1.12.The compound of any one of claims 2-11, or a pharmaceutically acceptable salt thereof, wherein each Y is independently selected from the group consisting of: Gly, D-Asp, Asp, D-Glu, Glu, D-γGlu, γGlu, and OEG.13.The compound of any one of claims 2-12, or a pharmaceutically acceptable salt thereof, wherein n is an integer of 1-10.14.The compound of any one of claims 2-13, or a pharmaceutically acceptable salt thereof, wherein n is an integer of 1-5.15.The compound of any one of claims 1-14, or a pharmaceutically acceptable salt thereof, wherein LA is a divalent linker comprising 1 to 5 Asp.16.The compound of claim 15, or a pharmaceutically acceptable salt thereof, wherein LA is a divalent linker comprising – (Asp) 2-5–.17.The compound of claim 15, or a pharmaceutically acceptable salt thereof, wherein LA is a divalent linker comprising – (D-Asp) 2-5–.18.The compound of claim 15, or a pharmaceutically acceptable salt thereof, wherein LA comprises 2 to 5 Asp, and wherein the 2 to 5 Asp is non-continuous in LA.19.The compound of claim 1 or claim 2, or a pharmaceutically acceptable salt thereof, wherein LA is a bond, -γGlu-γGlu-, -Glu-γGlu-, -Asp-, -Asp-Asp-, -γGlu-, -Gly-Ser-Gly-, -Asp-Asp-Asp-, -γGlu-γGlu-OEG-OEG-, -Asp-Asp-Gly-Gly-Gly-, -Asp-, -Glu-Glu-, - (D-Asp) - (D-Asp) -, -Gly-Gly-, -Asp-Asp-Asp-Asp-, -Cya-, -Gla-, -eLys-eLys-, -Ahx-Ahx-, -Gly-Ser-Gly-, or -Asp-Asp-OEG-.20.The compound of claim 1 or claim 2, or a pharmaceutically acceptable salt thereof, wherein LA is -Asp-Asp-, -Asp-Asp-Asp-, - (D-Asp) - (D-Asp) -, or -Asp-Asp-Asp-Asp-.21.The compound of any one of claims 1-20, or a pharmaceutically acceptable salt thereof, wherein T comprises one or more amino acid residues each independently selected from the group consisting of Lys, D-Lys, ornithine (Orn) , homo-lysine, 2, 3-diaminopropionic acid (Dap) , 2, 4-diaminobutyric acid (Dab) , cysteine, homo-cysteine, glutamine, glutamic acid, asparagine, aspartic acid, 3, 5-bis (aminomethyl) benzoic acid (Bab) , 4-aminomethylphenylalaline (Amp) , 4R-4-aminoproline (Apr) , 4- (2-aminoethoxy) phenylalanine, 4-aminopiperidine-4-carboxylic acid (Apc) , and 2- ( (1, 3-diaminopropan-2-yl) oxy) acetic acid (Dpa) .22.The compound of any one of claims 1-21, or a pharmaceutically acceptable salt thereof, wherein T is Lys, D-Lys, Amp, Apr, or Bab.23.The compound of any one of claims 1-21, or a pharmaceutically acceptable salt thereof, wherein T comprises Lys or D-Lys.24.The compound of any one of claims 1-21, or a pharmaceutically acceptable salt thereof, whereinwhen T comprises any of the amino acid residue selected from the group consisting of Lys, D-Lys, Orn, homo-lysine, 2, 3-diaminopropionic acid (Dap) , 2, 4-diaminobutyric acid (Dab) , cysteine, homo-cysteine, glutamine, glutamic acid, asparagine, aspartic acid, 4R-4-aminoproline (Apr) , and 4- (2-aminoethoxy) phenylalanine; thenA is conjugated toa amino group of T.25.The compound of any one of claims 1-21, or a pharmaceutically acceptable salt thereof, whereinwhen T comprises a Lys or D-Lys; thenA is conjugated toa amino group of the Lys or D-Lys.26.The compound of any one of claims 1-25, or a pharmaceutically acceptable salt thereof, wherein A is a fatty acid moiety.27.The compound of claim 26, or a pharmaceutically acceptable salt thereof, wherein A is a saturated fatty acid moiety.28.The compound of claim 26, or a pharmaceutically acceptable salt thereof, wherein A is a fatty monoacid moiety.29.The compound of claim 28, or a pharmaceutically acceptable salt thereof, wherein A is an unsubstituted or substituted C8-C18 fatty monoacid moiety.30.The compound of claim 28, or a pharmaceutically acceptable salt thereof, wherein A is an unsubstituted or substituted C10-C16 fatty monoacid moiety.31.The compound of claim 28, or a pharmaceutically acceptable salt thereof, wherein A is an unsubstituted or substituted C10 fatty monoacid moiety.32.The compound of claim 28, or a pharmaceutically acceptable salt thereof, wherein A is an unsubstituted or substituted C12 fatty monoacid moiety.33.The compound of claim 28, or a pharmaceutically acceptable salt thereof, wherein A is an unsubstituted or substituted C14 or a C16 fatty monoacid moiety.34.The compound of any one of claims 1-28, or a pharmaceutically acceptable salt thereof, wherein A is -C (O) Aa, wherein Aa is unsubstituted or substituted C3-C23 alkyl.35.The compound of claim 34, or a pharmaceutically acceptable salt thereof, wherein Aa is C7 alkyl, C8 alkyl, C9 alkyl, C10 alkyl, C11 alkyl, C12 alkyl, C13 alkyl, C14 alkyl, C15 alkyl, C16 alkyl, or C17 alkyl, each of which is unsubstituted or substituted.36.The compound of any one of claims 1-35, or a pharmaceutically acceptable salt thereof, wherein LZ is a bond or a divalent linker: – (X) m-,wherein:m is an integer of 1-20, andeach X is independently selected from the group consisting of an amino acid residue and -N (RN) (C2alkyleneXa) x1XbC (O) , wherein RN is H or C1-6 alkyl, wherein Xa is -O-, -S-, -NH-, or -N (C1-6 alkyl) -, wherein x1 is an integer from 1 to 10, and wherein Xb is C1-3 alkylene.37.The compound of any one of claims 1-36, or a pharmaceutically acceptable salt thereof, wherein LZ is a divalent linker comprising one or more amino acid residues.38.The compound of claim 37, or a pharmaceutically acceptable salt thereof, wherein LZ comprises one or more amino acid residues each independently selected from the group consisting of alanine (Ala, A) , asparagine (Asn, N) , glutamine (Gln, Q) , glycine (Gly, G) , isoleucine (Ile, I) , leucine (Leu, L) , methionine (Met, M) , phenylalanine (Phe, F) , proline (Pro, P) , serine (Ser, S) , threonine (Thr, T) , tryptophan (Trp, W) , tyrosine (Tyr, Y) , valine (Val, V) , pyrrolysine (Pyl, O) , pyrroline-carboxy-lysine (PCL) , NR5C5alkyleneC (O) (Ahx) , norleucine (Nle) , norvaline (Nva) , 2-aminooctanoic acid (Aoc) , 2-naphthylalanine (2-Nal) , 3- (trifluoromethyl) phenylalanine (TFP) , homophenylalanine (hPhe) , cyclohexylalanine (Cha) , 1-naphthylalanine (1-Nal) , 4-benzoyl-L-phenylalanine (Bpa) , 2-methoxy-4-vinylphenylalanine (MvF) , 4-fluorophenylalanine (4-F-Phe) , 4-phenyl-2, 3-dihydroxy-6-nitrophenylalanine (pNIPA) , 2- (2-naphthyl) alanine (2-Nal-ala) , 4- (4-propoxyphenyl) alanine (Ppa) , 4-carboxyphenylalanine (4-CPA) , 4-butylphenylalanine (Bua) , 2-nitrophenylalanine (2-Npa) , 4-azidophenylalanine (4-AzF) , 2- (4-nitrophenyl) ethylalanine (2-Npe) , 3-iodo-L-tyrosine (Ity) , and 5, 5, 5-trifluoroleucine (TFL) .39.The compound of claim 37 or 38, or a pharmaceutically acceptable salt thereof, wherein LZ comprise one or more neutral amino acid residues.40.The compound of claim 39, or a pharmaceutically acceptable salt thereof, wherein each of the neutral amino acid residues is independently Gly, D-Pro, Pro, D-Ser or Ser.41.The compound of any one of claims 1-40, or a pharmaceutically acceptable salt thereof, wherein LZ comprise one or more Gly.42.The compound of any one of claims 1-36, or a pharmaceutically acceptable salt thereof, wherein LZ comprises -N (RN) (C2alkyleneXa) x1XbC (O) , wherein RN is H, x1 is an integer from 1 to 10, and Xb is C1-C3 alkylene.43.The compound of claim 42, or a pharmaceutically acceptable salt thereof, wherein RN is H.44.The compound of claim 42 or claim 43, or a pharmaceutically acceptable salt thereof, wherein LZ comprises one or more moieties each independently selected from -NH (C2alkyleneO) 2C1alkyleneC (O) (OEG) , -NH (C2alkyleneO) C2alkyleneC (O) (PEG1) , -NH (C2alkyleneO) 3C2alkyleneC (O) (PEG3) , or -NH (C2alkyleneO) 6C2alkyleneC (O) (PEG6) .45.The compound of claim 36, or a pharmaceutically acceptable salt thereof, wherein each X is independently selected from the group consisting of Ahx, Gly, D-Ala, Ala, D-Val, Val, D-Leu, Leu, D-Phe, Phe, D-Pro, Pro, D-Met, Met, D-Trp, Trp, D-Thr, Thr, D-Tyr, Tyr, D-Nle, Nle, D-Ser, Ser, OEG and PEG1.46.The compound of claim 36 or claim 45, or a pharmaceutically acceptable salt thereof, wherein each X is independently selected from the group consisting of Gly, Pro, Ser, and OEG.47.The compound of any one of claims 36, 45, or 46, or a pharmaceutically acceptable salt thereof, wherein m is an integer of 1-15.48.The compound of any one of claims 36, 45, or 46, or a pharmaceutically acceptable salt thereof, wherein m is an integer of 1-10.49.The compound of any one of claims 36, 45, or 46, or a pharmaceutically acceptable salt thereof, wherein m is an integer of 1-6.50.The compound of any one of claims 1-49, or a pharmaceutically acceptable salt thereof, wherein LZ is a divalent linker comprising 1 to 6 OEG.51.The compound of any one of claims 1-49, or a pharmaceutically acceptable salt thereof, wherein LZ is a divalent linker comprising 1 to 6 Gly.52.The compound of claim 51, or a pharmaceutically acceptable salt thereof, wherein LZ is – (Gly) 2-5–.53.The compound of claim 51, or a pharmaceutically acceptable salt thereof, wherein LZ comprises 2 to 5 Gly, and the 2 to 5 Gly is non-continuous.54.The compound of any one of claims 1-53, or a pharmaceutically acceptable salt thereof, wherein LZ is a bond, -OEG-OEG-, -OEG-, -Gly-Gly-Gly-, -Gly-Ser-Gly-Ser-Gly-Ser-, -Pro-Gly-Pro-Gly-Pro-Gly-, -γGlu-γGlu -OEG-OEG-, -Asp-Asp-Gly-Gly-Gly-, -Gly-Gly-Gly-Gly-Gly-Gly-, -Gly-Tyr-Gly-, -Gly-Ser-Gly-, -Gly-, or -Gly-Gly-.55.The compound of any one of claims 1-53, or a pharmaceutically acceptable salt thereof, wherein LZ is -Gly-Gly-Gly-.56.The compound of any one of claims 1-55, or a pharmaceutically acceptable salt thereof, wherein E comprises a chemotherapeutic agent, a toxin, an immunomodulator, a diagnostic agent, a radionuclide, or a chelating group.57.The compound of claim 56, wherein E comprises a radionuclide selected from 14C , 15N , 18F , 75Br , 76Br , 77Br, 123I , 124I , 125I , 131I , 35S, 18F, 211At, 32P, 33P, and 125I.58.The compound of any one of claims 1-56, or a pharmaceutically acceptable salt thereof, wherein E comprises a chelating group derived from a chelating agent.59.The compound of claim 58, or a pharmaceutically acceptable salt thereof, wherein the chelating agent is selected from the group consisting of 1, 4, 7-Triazacyclononane (TACN) , 1, 4, 7-triazacyclononane-triacetic acid (NOTA) , 1, 4, 7-triazacyclononane-N-succinic acid-N', N"-diacetic acid (NOTASA) , 1, 4, 7-triazacyclononane-N-glutamic acid-N', N"-diacetic acid (NODAGA) , 1, 4, 7-triazacyclononane-N, N', N"-tris (methylenephosphonic) acid (NOTP) , 1, 4, 7, 10-tetraazacyclododecane ( [12] aneN4) (cyclen) , 1, 4, 7, 10-tetraazacyclotridecane ( [13] aneN4) , 1, 4, 7, 11-tetraazacyclotetradecane (iso-cyclam) , 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) , 2- (1, 4, 7, 10-tetraazacyclododecan-1-yl) acetate (DO1A) , 2, 2'- (1, 4, 7, 10-tetraazacyclododecane-1, 7-diyl) diacetic acid (DO2A) , 2, 2', 2"- (1 , 4, 7, 10-tetraazacyclododecane-1 , 4, 7-triyl) triacetic acid (DO3A) , 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetra (methanepnosphonic acid) (DOTP) , 1, 4, 7, 10-tetraazacyclododecane-1, 7-di (methanephosphoriic acid) (DO2P) , 1 , 4, 7, 10-tetraazacyclododecane-1, 4, 7-tri (methanephosphonic acid) (DO3P) , 1, 4, 7, 10-tetraazacyclo-decane-1 -glutamic acid-4, 7, 10-triacetic acid (DOTAGA) , 1, 4, 7, 10-tetraazacyclodecane-1 -succinic acid-4, 7, 10-triacetic acid (DOTASA) , 1, 4, 8, 11-tetraazacyclotetradecane ( [14] aneN4) (cyclam) , 1, 4, 8, 12-tetraazacyclopentadecane ( [15] aneN4) , 1, 5, 9, 13-tetraazacyclohexadecane ( [16] aneN4) , 1, 4-ethano-1, 4, 8, 11-tetraazacyclo-tetradecane (et-cyclam) , 1, 4, 8, 11-tetraazacyclotetradecane-1, 4, 8, 1 1-tetraacetic acid (TETA) , 2- (1, 4, 8, 11 -tetraazacyclotetradecane-1-y I) acetic acid (TE1A) , 2, 2'- (1, 4, 8, 11-tetraazacyclotetradecane-1, 8-diyl) diacetic acid (TE2A) , 4, 11-bis (carboxy methyl) -1, 4, 8, 11-tetraazabicyclo [6.6.2] -hexadecane (CB-TE2A) , 3, 6, 10, 13, 16, 19-hexaazabicyclo [6.6.6] icosane (Sar) , 1, 4, 7, 10-tetra- (2-carbamoyl-methyl) -cyclododecane (TCMC) , N, N′-bis [ (6-carboxy-2-pyridil) methyl] -4, 13-diaza-18-crown-6 (macropa) , phthalocyanines, porphyrins, PCTA (3, 6, 9, 15-tetraazabicyclo [9.3.1] pentadeca-1 (15) , 11, 13-triene-3, 6, 9-triacetic acid) , DEPA (7- [2- (biscarboxymethylamino) ethyl] -4, 10-biscarboxymethyl-1, 4, 7, 10-tetraazacyclododec-1-yl-acetic acid) , DTPA (1, 1, 4, 7, 7-diethylenetriaminepentaacetic acid) , CHX-DTPA (cyclohexane-1, 2-diamineN, N, N′, N′-tetraacetate) , BATPA (1, 2-bis [2-aminophenoxy] ethane-N, N, N′, N′-tetraacetic acid) , TTHA (triethylenetetramineN, N, N′, N″, N″′, N″′-hexaacetic acid) , HBED (N, N′-bis [2-hydroxybenzyl] ethylenediamine-N, N′-diacetic acid) , EGTA (ethylene glycol bis [2-aminoethyl ether] -N, N, N′, N′-tetraacetic acid) , EDTMP (ethylenediamine tetra- [methylene phosphonic acid] ) , TRAP (triazacyclononate phosphinic acids) , SHBED (N, N′-bis [2-hydroxy-5-sulfobenzyl] ethylenediaminediacetic acid) , H6Sbbpen (N, N′-bis- [2-hydroxy-5-sulfonylbenzyl] -N, N′-bis [2-methylpyridyl] ethylenediamine) , THP (Tris (3, 4-hydroxypyridinone) , DFO (deferoxamine) , FSC (Fusarinine) , 6SS (N, N′-bis [2, 2-dimethyl-2-mercaptoethyl] ethylenediamine-N, N′-diacetic acid) , ECC (ethylenecysteamine cysteine) , ECD (ethyl cysteinate dimer) , NETA ( [2- {4, 7-biscarboxymethyl (1, 4, 7) triazacyclonona-1-yl-ethyl} carbonylmethylamino] acetic acid, THPN (Tetrakis (3-Hydroxy-4-Pyridinone) ) , H2dedpa (1, 2- [ {6- (carboxylato-) pyridin-2-yl} methylamino] -ethane) , H4octapa (N, N-bis [6-carboxy-2-pyridylmethyl] -ethylenediamine-N, N′-diacetic acid) , H2bispa2 (6, 6′- [ {9-hydroxy-1, 5-bis- (methoxycarbonyl) -2, 4-di (pyridin-2-yl) -3, 7-diazabicyclo [3.3.1] nonane-3, 7-diyl} bis (methylene) ] dipicolinic acid) , DOTMP (1, 4, 7, 10-Tetraazacyclododecane-1, 4, 7, 10-tetrayl-tetrakis (methylphosphonic acid) ) , PEPA (1, 4, 7, 10, 13-pentaazocyclopentadecane pentaacetic acid) , HEHA (1, 4, 7, 10, 13, 16-hexaazocyclooctadecane hexaacetic acid) , H2hox, H2CHXhox, H2octox, H2pyhox, H4neunopa, TETPA, H4pypa, H4py4pa, DTPAm, EGTAm, ampam, Me-3, 2-HOPO, 3, 4, 3- (LI-1, 2-HOPO) , and macrocyclic tetrapthalimide.60.The compound of claim 59, or a pharmaceutically acceptable salt thereof, wherein the chelating group is derived from DOTA or DOTAGA.61.The compound of any one of claims 58-60, wherein the chelating group further complexes with one or more radionuclides, wherein the radionuclides are each independently a radioactive isotope of As, Se, K, Sc, Ti, Cr, Mn, Fe, Co, Ni, Cu, Ga, Ge, Rb, Sr, Y, Zr, Nb, Tc, Rh, Pd, In, Sn, Sb, Zn, Ta, W, Re, Os, Ir, Pt, Au, Hg, Tl, Pb, Bi, Po, Fr, Pm, a lanthanide, an actinide, Mg, Al, Ca, Cd, or Ba.62.The compound of claim 61, or a pharmaceutically acceptable salt thereof, wherein the lanthanide is Lu, Sm, Ho, or Tb.63.The compound of claim 61, or a pharmaceutically acceptable salt thereof, wherein the actinide is Ac, Th, or U.64.The compound of claim 61 or 62, or a pharmaceutically acceptable salt thereof, wherein the one or more radionuclides are each independently selected from the group consisting of 99Tc, 99mTc, 188Re, 186Re, 153Sm, 66Ga, 67Ga, 68Ga, 111In, 123In, 59Fe, 63Zn, 52Fe, 52Mn, 45Ti, 60Cu, 61Cu, 67Cu, 64Cu, 62Cu, 82Rb, 195mPt, 191mPt, 193mPt, 117mSn, 89Zr, 177Lu, 18F, 188Re, 186Re, 153Sm, 66Ho, 86Y , 87Y , 90Y, 89Sr, 153Gd, 159Gd, 225Ac, 212Bi, 213Bi, 198Au, 199Au, 193mPt, 197Pt, 103Pd, 109Pd, 105Rh, 101mRh, 103mRh, 223Ra, 224Ra, 97Ru, 227Th, 229Th, 161Tb, 149Tb, 203Pb, 212Pb, 201TI, 119Sb, 58mCo, 55Co, 57Co, 47Sc, 149Pm, 142Pr, 161Ho, 166Ho, 175Yb, and 51Cr.65.The compound of any one of claims 1-56 or 57-64, or a pharmaceutically acceptable salt thereof, wherein E is 177Lu-DOTA-, 177Lu-DOTAGA-, 225Ac-DOTA-, or225Ac-DOTAGA-.66.The compound of any one of claims 1-65, or a pharmaceutically acceptable salt thereof, wherein Z is: wherein:u is 0 or 1;R0 is C1-C6 alkyl substituted with one C6-C10 aryl, and the C6-C10 aryl is optionally substituted with one or more substituents, each substituent is independently halogen or NO2;R1 is C1-C6 alkyl substituted with one C6-C10 aryl, wherein the C6-C10 aryl is optionally substituted with one or more substituents, each substituent is independently -OH, -O (C1-C6 alkyl) , or -N (Ra) C (O) R1a, and wherein R1a is a 3 to 8-membered heterocycle optionally substituted with one or more oxo;R2 is C1-C6 alkyl substituted with one C6-C10 aryl or 5-to 12-membered heteroaryl, wherein the C6-C10 aryl or 5-to 12-membered heteroaryl is optionally substituted with one or more substituents, each substituent is independently -OH, -O (C1-C6 alkyl) , or -N (Ra) C (O) NH (Ra) ;x is 0 or 1;Rx is -N (Ra) C (O) - (C6-C10 aryl) ;R3 is C1-C6 alkyl substituted with one or more -NH (Ra) ;R4 is C1-C6 alkyl substituted with one or more -OH;y is 0 or 1;Ry is C1-C6 alkyl substituted with one C6-C10 aryl;Rz is -OH orwherein Rz1 is C1-C6 alkyl substituted with one or more substituents each independently selected from the group consisting of -OH and C6-C10 aryl optionally substituted with one or more -OH; Rz2 is -COOH, -C (O) NH2, or C1-C6 alkyl substituted with one or more -OH; andRa, at each occurrence, is independently H or C1-C3 alkyl.67.The compound of claim 66, or a pharmaceutically acceptable salt thereof, wherein u is 1, and R0 is C1-C6 alkyl substituted with one phenyl, wherein the phenyl is unsubstituted or substituted with one or more halogen.68.The compound of claim 66 or 67, or a pharmaceutically acceptable salt thereof, wherein R1 is methyl substituted with one C6-C10 aryl, wherein the C6-C10 aryl is optionally substituted with one or more substituents, each substituent is independently -OH or -NHC (O) R1a, wherein R1a is 3 to 8-membered heterocycle optionally substituted with one or more oxo.69.The compound of any one of claims 66-68, or a pharmaceutically acceptable salt thereof, wherein R2 is C1-C6 alkyl substituted with one C6-C10 aryl or 5-to 12-membered heteroaryl, wherein the C6-C10 aryl is optionally substituted with one or more substituents, each substituent is independently-OH or -NHC (O) NH2.70.The compound of any one of claims 66-69, or a pharmaceutically acceptable salt thereof, wherein R3 is C1-C6 alkyl substituted with one or more NH2.71.The compound of any one of claims 66-70, or a pharmaceutically acceptable salt thereof, wherein R4 is C1-C3 alkyl substituted with one or more -OH.72.The compound of any one of claims 1-65, or a pharmaceutically acceptable salt thereof, wherein Z is: 73.The compound of any one of claims 1-66, or a pharmaceutically acceptable salt thereof, wherein Z is: wherein R3a is CH2OH, CO2H, or CONH2.74.The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a structure of anyone selected from Table 1.75.The compound of any one of claims 1-74, or a pharmaceutically acceptable salt thereof, for use in imaging or diagnosing, or for use in therapy.76.A pharmaceutical composition, comprising the compound of any one of claims 1-74, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.77.A kit, comprising the compound of any one of claims 1-74, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 76, and instructions for using the kit to diagnose a disease or disorder in a subject in need thereof.78.A kit, comprising the compound of any one of claims 1-74, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 76, and instructions for using the kit to treat a disease or disorder in a subject in need thereof.79.A method of treating a disease or disorder in a subject in need thereof, comprising administering to the subject a pharmaceutical effective amount of one or more compounds of any one of claims 1-74 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 76.80.The method of claim 79, wherein the disease or disorder is cancer.81.The method of claim 79, wherein the cancer is a cancer with high expression of SSTR2.82.The method of claim 79, wherein the cancer is medullary thyroid carcinoma (MTC) , a small cell lung cancer (SCLC) or a neuroendocrine tumor.83.A method of inhibiting proliferative activity in a cell, comprising administering an effective amount of one or more compounds of any one of claims 1-74, or a salt thereof.84.A method of imaging a tissue in a subject by administering an imaging effective amount of one or more compounds of any one of claims 1-74, or a pharmaceutically acceptable salt thereof, to a subject in need thereof and applying an imaging technique to detect emitted gamma rays.85.A method of diagnosing cancer in subject by administering a diagnostic effective amount of one or more compounds of any one of claims 1-74, or a pharmaceutically acceptable salt thereof, and applying an imaging technique to detect emitted gamma rays.
Citation Information
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