[(68)Ga]Ga-DOTA-TOC Synthesis by a Cassette Developer System with [(68)Ga]GaCl(3) from Cyclotron using Liquid Target: An Italian Experience.

INTRODUCTION: [(68)Ga-DOTA-D-Phe1-Tyr3]octreotide ([(68)Ga]Ga-DOTA-TOC) is a somatostatin analogue largely used in PET/CT applications for the detection of gastroenteropancreatic neuroendocrine tumors (GEP-NET). Initially, it was obtained using a (68)Ge/(68)Ga generator. The increasing cost of good manufacturing practice-compliant generators has led to the need to find alternative ways of producing Gallium-68 ((68)Ga). The aim of this work is to show the production optimization of [(68)Ga]Ga-DOTA-TOC via cyclotron, derived from three years of experience. METHODS: The production of [(68)Ga]GaCl(3) via the (68)Zn(p,n)(68)Ga reaction was optimized using a PETtrace 800 cyclotron (equipped with ZnO liquid target) and the synthesis of [(68)Ga]Ga- DOTA-TOC was performed by FASTlab2 developer system according to the Guidelines on Good Radiopharmacy Practice (cGRPP). Quality control process was validated according to the current specific monograph (2482) of the European Pharmacopoeia (Ph. Eur.). RESULTS: [(68)Ga]Ga-DOTA-TOC was produced in 40 minutes; ten validation batches met the quality criteria expected by the Ph. Eur. The synthesis process has involved many issues due to the use of acidic reagents and related corrosion of some components of cyclotron and developer system, resulting in 12.2% failed syntheses and a target breakdown after 11 months. DISCUSSION: The main issues, their causes and the strategies used to solve them are reported in the troubleshooting section: thanks to these strategies, the number of failed syntheses has decreased, and today, we have achieved a 0% failure rate. CONCLUSION: Liquid target production of [(68)Ga]Ga-DOTA-TOC, once consolidated, instead of (68)Ge/(68)Ga generator has many advantages.