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

다국어 초록 (Multilingual Abstract)

Purpose One of the most interesting methods to deliver therapeutic doses of ionizing radiation to tumor sites is radiolabeledcompounds. Bombesin peptide binds to gastrin-releasing peptide receptors (GRPRs) with great affinity. Through itsappropriate physical characteristics and accessibility as the 188W/188Re generator, 188Re can be effectively used to develop atherapeutic radio complex. In this study, 188Re-HYNIC-BBN was prepared under optimal conditions.
Methods 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 andHPLC. The stability of the radio-complex was checked in PBS buffer (4 °C) and human blood serum (37 °C). The partitioncoefficient of the final radio-complex was studied using standard procedure. Finally, the biodistribution of 188Re-HYNICBBNand free 188Re 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 theoptimized conditions (pH = 4–5, reaction time = 45 min, temp = 95℃). This radio-complex was found to be stable in PBSand blood serum over 24 h. LogPo/w was − 1.78, showing the high hydrophilic nature of the radio-complex. The biodistributionof 188Re-HYNIC-BBN demonstrated the fast clearance of the radio-peptide from the blood circulation. The most portionof the radioactivity was excreted from the body via the urinary tract and the remaining activity was accumulated in GRPRexpressingorgans.
Conclusion The special characteristics of the complex introduce 188Re-HYNIC-BBN as a new therapeutic agent for targetingGRPRs, however, more biological data is still needed.