Improved Automated Radiosynthesis of [F]Dolutegravir: Toward Clinical Applications.

Positron emission tomography imaging using radiolabeled dolutegravir (DTG) is an interesting approach to understand the biodistribution of this antiretroviral drug at HIV-1 sanctuary sites. In the course of clinical translation, we depict herein an improved and pharmaceutically compliant radiosynthesis of [F]DTG from an original tin precursor. The radiosynthesis was achieved in two steps by copper-mediated radiofluorination, followed by enol ether deprotection using a kit-based AllInOne module. Ready-to-inject [F]DTG was obtained in 20 ± 5% ( = 12) decay-corrected radiochemical yield within 90 min, representing a 4-fold increase compared to the previously published three-step radiosynthesis. Quality control was carried out with three consecutive [F]DTG productions according to the current European Pharmacopoeia guidelines, which include pH determination, identity and purity (chemical, radiochemical, and radionuclide) assessments, residual solvent quantification, dosage of lithium, copper, and tin traces, sterility and bacterial endotoxin tests. [F]DTG (∼2 GBq) was obtained with a molar activity of 59 ± 2 GBq/μmol at the time of injection and was suitable for human applications.