COMPARATIVE IN VITRO AND IN VIVO EVALUATION OF A SERIES OF NOVEL BOMBESIN-LIKE PEPTIDES

摘要

Bombesin (BN) is a peptide exhibiting a high affinity for the gastrin releasing peptide (GRP) receptor, which is overexpressed by a variety of tumours, such as breast or prostate cancer. The aim of the present work is the study of a series of novel BN-like peptides, by investigation of the radiochemical and radiopharmacological behaviour of the complexes they form with the nuclides ~(185/187)Re and ~(99m)Tc. The derivatives under study are: BN1: Cys-Aca-BN[2-14], BN1.1: Gly-Gly-Cys-,4ca-BN[2-14], BN1.2: MeGly-Gly-Cys-Aca-BN[2-14], BN1.3: (Me)_2Gly-Gly-Cys-Aca-BN[2-14] and BN1.4: Cys-Gly-Cys-Aca-BN[2-14] where Aca represents 6-amino-n-hexanoic acid. The ~(185/187)Re complexes were formed via the precursor Re-gluconate. The radiolabelling of the derivatives with ~(99m)Tc was performed via the precursor ~(99m)Tc-gluconate. The authors' efforts were focused on the comparative assessment of the radiolabelling conditions of the BN analogues with ~(99m)Tc, so that the final radiolabelled products could have the maximum specific activity. The stability of the radiolabelled products was studied over time. The capability of the new peptides to tag cancer cells was evaluated in epithelial prostate cancer cells (PC3). Thus, the authors examined whether the new BN-derivatives, as well as their complexes with ~(185/187)Re, inhibit [~(125)I-Tyr~4]-BN binding. The in vivo behaviour of the ~(99m)Tc labelled BN-like peptides was evaluated in normal mice. In addition, for the most promising radiolabelled peptide the stability in human plasma was studied. Also, biodistribution and scintigraphic studies were assessed in prostate cancer models.