A convenient production of clinical grade ⁶⁸Ga-labeled Bombesin in an automated cassette-based platform.

Objectives Similarly to radiolabeled somatostatin-based antagonists that have been growing in popularity, the bombesin family of G-protein coupled receptor ligands has shown high and specific uptake in gastrin-releasing peptide receptor (GRPr)-positive tumors. The DOTA-conjugated bombesin antagonist RM2 (DOTA-(4-amino-piperidin-1-yl)-acetyl-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) has been radiolabeled with ⁶⁸Ga for imaging of prostate tumors with positron emission tomography (PET). We seek approval for clinical radiochemistry via the RDRC (Radioactive Drug Research Committee) at Stanford to allow us to study the first patients in the United States with GRPr-positive tumors using ⁶⁸Ga-RM2.

Methods We produced ⁶⁸Ga-labeled RM2 using an automated cassette-based platform. ⁶⁸Ga is eluted from a ⁶⁸Ge/⁶⁸Ga generator and trapped via a cation exchange cartridge. A concentrated NaCl/HCl solution is used to elute the ⁶⁸Ga from the cartridge for the subsequent radiolabeling step. After the final product is purified by solid phase extraction, it is formulated and sterilized for injection. Quality control and release criteria were set according to USP<823>.

Results The cassette-based synthesis takes less than 25 minutes from elution to final formulation with good consistency in quality of final product (radiochemical purity by HPLC = 97.6% ± 0.6% (n = 3), chemical impurities other than residual precursor undetectable). The radiochemical yield was 85% ± 2% (decay-corrected to start-of-synthesis, n=3). The final formulated batches passed all quality controls and met the set release criteria.

Conclusions We implemented a relatively simple and reliable ⁶⁸Ga-radiochemistry for producing clinical-grade ⁶⁸Ga-RM2 on a cassette-based platform. Three consecutive and successful validation runs were performed in compliance with USP<823>. We will submit these results with a RDRC application to provide a new avenue to image GRPr-positive tumors in the United States.