Fully automated and reproducible radiosynthesis of high specific activity [¹¹C]raclopride and [¹¹C]Pittsburgh compound-B using the combination of two commercial synthesizers

Abstract

Introduction: The use of ¹¹C-labeled radiotracers in routine positron emission tomography studies is dependent on the production capability of radiochemistry laboratories. Therefore, considerable efforts are being focused on the development of fast, efficient, and robust methods for the preparation of such radiotracers.

Methods: The fully automated syntheses of [¹¹C]raclopride and [¹¹C]Pittsburgh compound-B (PIB) starting from cyclotron-produced [¹¹C]CH4 are reported. [¹¹C]methyl iodide and [¹¹C]methyl triflate were produced in the TRACERlab FXC Pro synthesis box. Methylation reactions and the final formulation were performed using the AutoLoop (captive solvent method) and the ReFORM-plus systems, respectively.

Results: [¹¹C]raclopride (n=30) and [¹¹C]PIB (n=24) were synthesized by O-[¹¹C]-methylation and N-[¹¹C]-methylation of (S)-O-desmethylraclopride and 6-OH-BTA-0 using [¹¹C]methyl iodide and [¹¹C]methyl triflate, respectively. Good radiochemical yields (51.3 ± 11.2 and 32.9 ± 6.6%, referred to as [¹¹C]methyl iodide, decay corrected) and specific activities (109 ± 20 and 143 ± 26 GBq/µmol) were obtained for [¹¹C]raclopride and [¹¹C]PIB, respectively, in a fully automated process. Radiochemical purity was higher than 99% in all cases.

Conclusion: The fast, robust and fully automated processes reported here allow [¹¹C]raclopride and [¹¹C]PIB synthesis with good radiochemical yields and high specific activities. Consecutive productions can be performed with minimal intervention on the synthesis modules and minimal exposure to radiation.