Cleavable radioligands for targeting cell surface receptors and uses thereof

A compound of Formula I, or a pharmaceutically acceptable salt or solvate thereof,

• wherein
• A is an albumin binding group selected from the group consisting of
• unsubstituted or substituted C(O)C1-26alkyleneCO2H, unsubstituted or substituted C(O)C2-26alkenyleneCO2H, unsubstituted or substituted C(O)C1-26alkyl, and unsubstituted or substituted C(O)C2-26alkenyl;
• Z is a tumor binding group, wherein the tumor binding group is a prostate specific membrane antigen (PSMA) binding group, a glucagon-like peptide-1 receptor (GLP-1R) binding group, or a glucose-dependent insulinotropic polypeptide (gastric inhibitory polypeptide;
• GIP) receptor (GIP-R) binding group;
• E is a chelating group;
• T is a branching group that is at least trivalent, wherein T is an amino acid residue derived from lysine, ornithine, homo-lysine, 2,3-diaminopropionic acid (DAP), 2,4-diaminobutyric acid (DAB), cysteine, homo-cysteine, glutamine, or trimesic acid (TMA);
• LA and LE are each independently a direct bond, a cleavable linker or a non-cleavable linker, wherein the non-cleavable linker comprises one or more groups selected from one or more amino acids residues derived from Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, Val, Pyl, Sec or PCL or the D enantiomers thereof;
• one or more amino acids residues derived from DAB or DAP;
• OEG, R1NC1-20alkyleneNR2, C(O)C1-20alkyleneC(O), R1NC1-20alkyleneC(O), and C(O)C1-20alkyleneNR2, wherein each R1 and R2 is independently selected from H and C1-2alkyl;
• and
• LZ is a direct bond or a non-cleavable linker, wherein the non-cleavable linker comprises one or more of amino acid residues, R1NC1-20alkyleneNR2, R1NC1-20alkenyleneNR2, C(O)C1-20alkyleneC(O), C(O)C1-20alkenyleneC(O), R1NC1-20alkyleneC(O), R1NC1-20alkenyleneC(O), C(O)C1-20alkyleneNHR2, C(O)C1-20alkenyleneNR2, C(S)C1-20alkyleneC(S), C(S)C1-20alkenyleneC(S), C(S)C1-20alkyleneC(O), C(S)C1-20alkenyleneC(O), C(O)C1-20alkyleneC(S), C(O)C1-20alkenyleneC(S), C(O)C1-20alkyleneO, C(O)C1-20alkenyleneO, R1NC1-20alkenyleneC(S), C(S)C1-20alkyleneNR2 and C(S)C1-20alkenyleneNR2, the latter 19 groups being optionally interrupted by one or more of S, O, NH, N(C1-6alkyl), C(O), C(O)NH, NHC(O), C(S)NH, NHC(S), NHC(O)NH, NHC(S)NH, NHC(NH), NHC(NC1-4alkyl), C(NH)NH, C(NC1-4alkyl)NH, NC4-10cycloalkyl, C4-10heterocycloalkyl, C6-10aryl and C5-10heteroaryl, and each alkyl, alkylene and alkenylene is optionally substituted with one or more substituents selected from halo, CO2H, C1-6alkyl, OH, OC1-6alkyl, SH, SC1-6alkyl, NR3R4, C1-4alkyleneOH, C1-4alkyleneOC1-4alkyl and C1-4alkyleneNR3R4, wherein each R1, R2, R3 and R4 is independently selected from H and C1-4alkyl;
• provided at least one of LA and LE is a cleavable linker, wherein the cleavable linker comprises at least one cleavable moiety, and the cleavable moiety is
• wherein each
• is a point of connection as set forth in the compound of Formula I.