Cossandi Michela, Statuto Massimo, Biasiotto Giorgio, Vigano Gian Luca, Camoni Luca, Migliorati Elena, Rodella Carlo, Saiani Federica, Spiazzi Luigi, Bertagna Francesco
Nuclear Medicine, ASST Spedali Civili di Brescia, Brescia, Italy.
Highly Specialized Laboratory, ASST Spedali Civili di Brescia, University of Brescia, Brescia, Italy.
Curr Radiopharm. 2025;18(4):302-317. doi: 10.2174/0118744710379515250506045145.
[Ga-DOTA-D-Phe1-Tyr3]octreotide ([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 Ge/Ga generator. The increasing cost of good manufacturing practice-compliant generators has led to the need to find alternative ways of producing Gallium-68 (Ga). The aim of this work is to show the production optimization of [Ga]Ga-DOTA-TOC via cyclotron, derived from three years of experience.
The production of [Ga]GaCl via the Zn(p,n)Ga reaction was optimized using a PETtrace 800 cyclotron (equipped with ZnO liquid target) and the synthesis of [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.).
[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.
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.
Liquid target production of [Ga]Ga-DOTA-TOC, once consolidated, instead of Ge/Ga generator has many advantages.
[镓 - DOTA - D - 苯丙氨酸1 - 酪氨酸3]奥曲肽（[镓]镓 - DOTA - TOC）是一种生长抑素类似物，在正电子发射断层扫描/计算机断层扫描（PET/CT）应用中广泛用于检测胃肠胰神经内分泌肿瘤（GEP - NET）。最初，它是使用锗/镓发生器获得的。符合药品生产质量管理规范的发生器成本不断增加，导致需要寻找生产镓 - 68（Ga）的替代方法。这项工作的目的是展示基于三年经验通过回旋加速器对[镓]镓 - DOTA - TOC进行的生产优化。
使用PETtrace 800回旋加速器（配备氧化锌液体靶）优化通过锌（p，n）镓反应生产[镓]氯化镓，并根据良好放射性药物生产规范指南（cGRPP）由FASTlab2显影系统进行[镓]镓 - DOTA - TOC的合成。根据欧洲药典（Ph. Eur.）当前的特定专论（2482）对质量控制过程进行验证。
[镓]镓 - DOTA - TOC在40分钟内生产出来；十个验证批次符合欧洲药典预期的质量标准。由于使用酸性试剂以及回旋加速器和显影系统某些部件的相关腐蚀，合成过程涉及许多问题，导致12.2%的合成失败，并且11个月后靶发生故障。
故障排除部分报告了主要问题、其原因以及用于解决这些问题的策略：由于这些策略，合成失败的数量减少了，如今，我们已实现0%的失败率。
[镓]镓 - DOTA - TOC的液体靶生产一旦巩固，相对于锗/镓发生器具有许多优势。
