MODIFIED BOMBESIN ANALOGUE WITH TECHNETIUM TRICARBONYL PRECURSOR AS PROSTATIC RADIODIAGNOSTIC AGENT

摘要

Bombesin (BBN) and the molecularly related gastrin releasing peptide act as neurotransmitters and endocrine cancer cell growth factors on normal tissues as well as on neoplastic cells of various origins, including prostatic carcinomas and many breast carcinomas. The aim of the study was the evaluation of the labelling and biodistribution of modified BBN analogue with Tc-carbonyl core as a prostatic tumour diagnostic agent. BBN (7-14) was synthesized by substituting methionine (14) by norleucine and coupling the (NaHis)Ac ligand for application of the Tc-carbonyl labelling technique. Radiochemical evaluation was done and biodistribution studies were performed in normal Swiss mice at 1.5, 4 and 24 h post-injection, and in nude mice bearing prostate cancer cells PC-3, 1.5 h post-injection. The yield of the tricarbonyl intermediate was greater than 90%. Radiochemical purity for the radiolabelled BBN was 86.3 ± 1.2%. Biodistribution study results suggest that ~(99m)Tc(CO)_3-BBN was mainly excreted by the hepato-biliary system and had high intestinal uptake. Tumour uptake was 1.15 ± 0.05% ID/g with tumounblood and tumounmuscle ratios of 2.67 and 3.19, respectively. Scinti-graphic imaging in nude mice bearing PC-3 cells showed a very low uptake by the tumour. Labelling conditions permitted a good yield. Nevertheless, the radiopharmaceutical did not show improved uptake by prostatic cell tumour, in comparison with findings observed without the modification in the molecule.