Optimized Production of Re-HYNIC-Bombesin: New Therapeutic Agent for GRPR Targeting.

PURPOSE

One of the most interesting methods to deliver therapeutic doses of ionizing radiation to tumor sites is radiolabeled compounds. Bombesin peptide binds to gastrin-releasing peptide receptors (GRPRs) with great affinity. Through its appropriate physical characteristics and accessibility as the W/Re generator, Re can be effectively used to develop a therapeutic radio complex. In this study, Re-HYNIC-BBN was prepared under optimal conditions.

METHODS

Optimization of the effective parameters on Re-HYNIC-BBN radio-labeling yield like ligand concentration, pH, reaction time, and temperature were performed. The final product's radiochemical purity was measured by RTLC and HPLC. The stability of the radio-complex was checked in PBS buffer (4 °C) and human blood serum (37 °C). The partition coefficient of the final radio-complex was studied using standard procedure. Finally, the biodistribution of Re-HYNIC-BBN and free Re in different organs of the rats were compared in various intervals.

RESULTS

The final product was prepared with a specific activity of 7.11 TBq/mmol and radiochemical purity > 95% at the optimized conditions (pH = 4-5, reaction time = 45 min, temp = 95℃). This radio-complex was found to be stable in PBS and blood serum over 24 h. LogP was - 1.78, showing the high hydrophilic nature of the radio-complex. The biodistribution of Re-HYNIC-BBN demonstrated the fast clearance of the radio-peptide from the blood circulation. The most portion of the radioactivity was excreted from the body via the urinary tract and the remaining activity was accumulated in GRPR-expressing organs.

CONCLUSION

The special characteristics of the complex introduce Re-HYNIC-BBN as a new therapeutic agent for targeting GRPRs, however, more biological data is still needed.