Optimized Production of ¹⁸⁸Re-HYNIC-Bombesin: New Therapeutic Agent for GRPR Targeting

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 ¹⁸⁸W/¹⁸⁸Re generator, ¹⁸⁸Re can be effectively used to develop a therapeutic radio complex. In this study, ¹⁸⁸Re-HYNIC-BBN was prepared under optimal conditions.

Optimization of the effective parameters on ¹⁸⁸Re-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 ¹⁸⁸Re-HYNIC-BBN and free ¹⁸⁸Re in different organs of the rats were compared in various intervals.

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_o/w was - 1.78, showing the high hydrophilic nature of the radio-complex. The biodistribution of ¹⁸⁸Re-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.

The special characteristics of the complex introduce ¹⁸⁸Re-HYNIC-BBN as a new therapeutic agent for targeting GRPRs, however, more biological data is still needed.