Improved Automated\nRadiosynthesis of [<sup>18</sup>F]Dolutegravir:\nToward Clinical Applications

Positron emission\ntomography imaging using radiolabeled dolutegravir\n(DTG) is an interesting approach to understand the biodistribution\nof this antiretroviral drug at HIV-1 sanctuary sites. In the course\nof clinical translation, we depict herein an improved and pharmaceutically\ncompliant radiosynthesis of [<sup>18</sup>F]DTG from an original tin\nprecursor. The radiosynthesis was achieved in two steps by copper-mediated\nradiofluorination, followed by enol ether deprotection using a kit-based\nAllInOne module. Ready-to-inject [<sup>18</sup>F]DTG was obtained\nin 20 ± 5% (<i>n</i> = 12) decay-corrected radiochemical\nyield within 90 min, representing a 4-fold increase compared to the\npreviously published three-step radiosynthesis. Quality control was\ncarried out with three consecutive [<sup>18</sup>F]DTG productions\naccording to the current European Pharmacopoeia guidelines, which\ninclude pH determination, identity and purity (chemical, radiochemical,\nand radionuclide) assessments, residual solvent quantification, dosage\nof lithium, copper, and tin traces, sterility and bacterial endotoxin\ntests. [<sup>18</sup>F]DTG (∼2 GBq) was obtained with a molar\nactivity of 59 ± 2 GBq/μmol at the time of injection and\nwas suitable for human applications.