Synthesis and Radiopharmacological Evaluation of ¹⁸F-labeled Bombesin Analog [¹⁸F]BX-00374436 for Imaging of GRP Receptor-Expression Prostate Cancer

Objectives: Over the last two decades, radiolabeled peptides have been widely used as promising radiotracers for tumor targeting. In recent years, bombesin and bombesin analogs have attracted much attention as high affinity and selectivity ligands for the gastrin-releasing peptide (GRP) receptor. The GRP receptor was found to be overexpressed and implicated in a variety of human tumors. Radiolabeled bombesin and bombesin analogs represent an interesting class of diagnostic probes for molecular imaging of GRP receptor-expressing prostate cancer. This work is aimed at the development of an ¹⁸F-labeled bombesin analog for molecular imaging GRP receptors in prostate cancer xenografts.
Methods: Aminopentanoic acid-modified bombesin analog BX-06053011 was conjugated with the bifunctional labeling agent N-succinimidyl-4-[¹⁸F]fluorobenzoate ([¹⁸F]SFB) in borate buffer (pH = 8.2) for 30 min at 50 °C to give the desired ¹⁸F-labeled bombesin analog [¹⁸F]BX-00374436 (Fig. 1). Tumor-targeting of radiolabeled bombesin analog [¹⁸F]BX-00374436 was evaluated in male nude mice bearing human prostate cancer (PC3) by means of biodistribution and dynamic small animal PET studies.
Results: ¹⁸F-labeled bombesin analog [¹⁸F]BX-00374436 was prepared in 30% radiochemical yield (based upon [¹⁸F]SFB) within 80 min including HPLC purification, evaporation of HPLC eluent and formulation in 0.9% saline. The radiochemical purity exceeded 95%, and the specific activity was 20 GBq/μmol. The binding affinity (KD) of fluorobenzoylated bombesin BX-00374436 was determined to be 0.7 nM. Radiotracer [¹⁸F]BX-00374436 showed reasonable metabolic stability in mouse blood, being 65% of intact radiolabeled peptide after 60 min. Tumor uptake of [¹⁸F]BX-00374436 in PC3 tumor bearing nude mice was 2.75 %ID/g after 5 min p.i., and 2.45 %ID/g after 60 min p.i. The receptor specificity of radiotracer [¹⁸F]BX-00374436 could be demonstrated by effective blocking of tumor uptake in the presence of non-radioactive BX-00374436. Dynamic small animal PET imaging confirmed specific radiotracer uptake in the PC3 tumor.
Conclusions: The present study showed that ¹⁸F-labeled bombesin analog [¹⁸F]BX-00374436 is a suitable radiotracer for molecular imaging of GRP receptor-positive prostate cancer by means of PET.