Automated two-step manufacturing of [11C]glyburide radiopharmaceutical for PET imaging in humans

International audienceIntroduction: Glyburide is an approved anti-diabetes drug binding to the sulfonylurea receptors-1 (SUR-1) and substrate of solute carrier (SLC) transporters, which can be isotopically radiolabelled with carbon-11 for PET imaging. The aim of this work is to present an original and reproducible automated radiosynthesis of [ 11 C]glyburide and a full European Pharmacopeia 9.7 compliant quality control to use [ 11 C]glyburide in PET imaging clinical trials.Methods: Different conditions were explored to afford non-radioactive glyburide by one or two-step methylation. These experiments were monitored by UPLC-MS. The optimized process was applied to the automated radiosynthesis of [ 11 C]glyburide using a TRACERlab® FX C Pro. A complete quality control according to Pharmacopeia guidelines was realized.Results: One-step methylation revealed regioselectivity issues as methylation occurred preferentially on the sulfonylurea moiety. Two-step approach by methylation followed by reaction with cyclohexyl isocyanate afforded glyburide without formation of methylated side products. Ready-to-inject [ 11 C]glyburide was obtained in 5% non-decay corrected radiochemical yield and 110 ± 20 GBq/μmol molar activity within 40 min (n = 8). [ 11 C] Glyburide quality control was compliant with the Pharmacopeia requirements.Conclusions: We have described a highly reproducible and automated two-step radiosynthesis of [ 11 C]glyburide which was qualified as a radiopharmaceutical for human injection. This whole manufacturing process is currently being used to conduct a clinical trial to elucidate the hepatic transport of drugs. Advances in knowledge: Compared to previously reported radiosynthesis of [ 11 C]glyburide, this work provides an original and reproducible approach which can be transferred to any PET centre interested in using this radiotracer for preclinical or clinical imaging.Implication for patient care: This work provides a method to manufacture [ 11 C]glyburide for human PET imaging. This radiopharmaceutical could be used to elucidate the role of transporters in drug exposure of different organs or to monitor brain recovery after central nervous system (CNS) injuries