[68Ga]Ga-DOTA-TOC Synthesis by a Cassette Developer System with [68Ga]GaCl3 from Cyclotron using Liquid Target: An Italian Experience.

Abstract

Background: [68Ga-DOTA-D-Phe1-Tyr3]octreotide ([68Ga]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 68Ge/68Ga generator.

Objective: The increasing cost of good manufacturing practice-compliant generators has led to the need to find alternative ways of producing Gallium-68 (68Ga). The goal of this work is to show the production optimization of [68Ga]Ga-DOTA-TOC via cyclotron, derived from three years of experience.

Methods: The production of [68Ga]GaCl3 via the 68Zn(p,n)68Ga reaction was optimized using a PETtrace 800 cyclotron (equipped with ZnO liquid target) and synthesis of [68Ga]Ga-DOTATOC 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.) before clinical use.

Results: [68Ga]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 the cyclotron and developer system, resulting in 12.2% failed syntheses and a target breakdown after 11 months. In the troubleshooting section are reported the main issues, their causes and the strategies used to solve them. 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 [68Ga]Ga-DOTA-TOC, once consolidated, instead of 68Ge/68Ga generator has many advantages.