RADIOLABELED BOMBESIN-DERIVED COMPOUNDS FOR IN VIVO IMAGING OF GASTRIN-RELEASING PEPTIDE RECEPTOR (GRPR) AND TREATMENT OF GRPR-RELATED DISORDERS

摘要

There is provided bombesin-derived compounds of Formula Ia (RX-L-Xaa1-Gln-Trp-Ala-Val-Xaa2-His-Xaa3-ψ-Xaa4-NH2). RX comprises a radionuclide chelator or a trifluoroborate-containing prosthetic group. L is a linker. Xaa1 is D-Phe, Cpa (4-chlorophenylalanine), D-Cpa, Tpi (2,3,4,9-tetrahydro-1H-pyrido[3,4b]indol-3-carboxylic acid), D-Tpi, Nal (naphthylalanine), or D-Nal. Xaa2 is Gly, N-methyl-Gly or D-Ala. Xaa3 is Leu, Pro, D-Pro, or Phe. Xaa4 is Pro, Phe, Tac (thiazolidine-4-carboxylic acid), Nle (norleucine), 4-oxa-L-Pro (oxazolidine-4-carboxylic acid). The symbol ψ represents a reduced peptide bond between Xaa3 and Xaa4 in which ψ is CH2—N when Xaa4 is Pro, Tac or 4-oxa-L-Pro, or ψ is CH2N(R) when Xaa4 is Phe or Nle wherein R is H or C1-C5 linear or branched alkyl. There is also provided the use of such compounds as imaging agents or therapeutic agents.