Nucl Med Mol Imaging.  2024 Oct;58(5):300-309. 10.1007/s13139-024-00866-1.

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

• Vosoughi S
• Salek N
• Zolghadri S
• Aghamiri SMR
• Delavari M

• KMID: 2560636
• DOI: http://doi.org/10.1007/s13139-024-00866-1

Abstract

Purpose
One of the most interesting methods to deliver therapeutic doses of ionizing radiation to tumor sites is radiola- beled compounds. Bombesin peptide binds to gastrin-releasing peptide receptors (GRPRs) with great affinity. Through its appropriate physical characteristics and accessibility as the ¹⁸⁸W/¹⁸⁸ Re generator, ¹⁸⁸Re can be effectively used to develop a therapeutic 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 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-HYNICBBN and 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 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 biodistribu- tion 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.
Conclusion
The special characteristics of the complex introduce ¹⁸⁸Re-HYNIC-BBN as a new therapeutic agent for target- ing GRPRs, however, more biological data is still needed.

Keyword

¹⁸⁸W/¹⁸⁸Re Generator; GRPR; HYNIC-BBN; Radio-labeling; Targeted radiation therapy