Routine Automated Synthesis of Lu-177 BB2r Radiopharmaceuticals: A Feasibility Study

1126 Objectives Bombesin receptor radiopharmaceuticals are currently being developed for theranostic applications for use in diagnosing and treating BB2r positive neoplastic tissue. Clinical use of these radiopharmaceuticals will necessitate routine production of therapeutic radiopharmaceuticals in high yields and purity suitable for clinical research and clinical testing. This study evaluates and demonstrates the capability to routinely produce a BB2r theranostic radiopharmaceutical, Lu-177-RM2 for preclinical and clinical research evaluation using a commercial automated radiochemical synthesizer. Methods DOTA-4-amino-1-carboxymethyl-piperidine-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (RM2), a potent BB2r antagonist, was commercially synthesized and evaluated for chemical purity using HPLC and mass spectrometry.Lu-177-chloride was obtained from two different venders, either Perkin Elmer (Product # NEZ347) or the Missouri University Research Reactor (MURR). RM2 was radiolabeled with Lu-177-chloride using the automated Eckert & Ziegler Modular-Lab PharmTracer employing a sterile synthesis cassette designed for Lu-177 DOTA drug synthesis. The Lu-177 synthesis cassette was used as supplied from the vender. All chemicals used in the radiosynthesis including ascorbic acid buffer, ethanol, saline, and water, were sterile and USP grade or equivalent. The final product was evaluated for radiochemical purity using HPLC, radionuclidic identity, and particulates. Product specific activity was determined using a standard dose calibrator. Results Radiosyntheses were performed on concentrations of Lu-177 ranging from 248 to 3959 MBq. The use of the automated Eckert & Ziegler Modular-Lab PharmTracer cassette system for the synthesis of Lu-177-RM2 produced consistent yields of 82.7 +/- 4.9% (n=14) product. Radiochemical purity of the resultant Lu-177 radiopharmaceuticals was 97.7 +/- 4.3 % (n=14) over the range of Lu-177 activities tested. Final product specific activity ranged from 20.7 to 329.9 MBq/ml. Radiopharmaceutical product integrity of >90% was maintained for up to one week post synthesis when Lu-177-RM2 was reconstituted following storage in liquid nitrogen. Conclusions High yield and purity Lu-177-RM2 can be effectively produced using a commercially available automated radiochemical synthesis system. Utilizing sterile single use radiosynthesis cassettes provides an easy and effective method for the routine production of clinical grade Lu-177-RM2 to support the translation of this therapeutic radiopharmaceutical into the clinical arena.