Enhanced radiosyntheses of [¹¹C]raclopride and [¹¹C]DASB using ethanolic loop chemistry

Abstract

Introduction: To improve the synthesis and quality control of carbon-11 labeled radiopharmaceuticals, we report the fully automated loop syntheses of [¹¹C]raclopride and [¹¹C]DASB using ethanol as the only organic solvent for synthesis module cleaning, carbon-11 methylation, HPLC purification, and reformulation.

Methods: Ethanolic loop chemistry is fully automated using a GE TRACERLab FX(C-Pro) synthesis module, and is readily adaptable to any other carbon-11 synthesis apparatus. Precursors (1 mg) were dissolved in ethanol (100 μL) and loaded into the HPLC loop. [¹¹C]MeOTf was passed through the HPLC loop and then the labeled products were purified by semi-preparative HPLC and reformulated into ethanolic saline.

Results: Both [¹¹C]raclopride (3.7% RCY; >95% RCP; SA=20831 Ci/mmol; n=64) and [¹¹C]DASB, both with (3.0% RCY; >95% RCP; SA=15152Ci/mmol; n=9) and without (3.0% RCY; >95% RCP; SA=10931 Ci/mmol; n=3) sodium ascorbate, have been successfully prepared using the described methodology. Doses are suitable for human use and the described methods are now employed for routine clinical production of both radiopharmaceuticals at the University of Michigan.

Conclusions: Ethanolic loop chemistry is a powerful technique for preparing [¹¹C]raclopride and [¹¹C]DASB, and we are in the process of adapting it for other carbon-11 radiopharmaceuticals prepared in our laboratories ([¹¹C]PMP, [¹¹C]PBR28 etc.).