Radiosynthesis of the HIV integrase inhibitor [18F]MK-0518 (Isentress)

The human immunodeficiency virus integrase inhibitor, [18F]MK‐0518, was prepared via a three‐step, one‐pot radiosynthesis. [18F]4‐Fluorobenzylamine was produced from the fluorination of 4‐cyano‐N,N,N‐trimethylammonium triflate with [18F]fluoride and reduction with borane methylsulfide complex in 50–68% radiochemical yield. The final step, the coupling of [18F]4‐fluorobenzylamine with an ester coupling partner, achieved an overall uncorrected radiochemical yield after HPLC purification of ∼2%, based on the starting [18F]fluoride. In a typical run, the total synthesis time was about 90 min and gave 0.37–1.74 GBq (10–47 mCi) of [18F]MK‐0518. The radiochemical purity of [18F]MK‐0518 was>98% and the specific activity was 243–1275 Ci/mmol (EOS, n=4). A convenient three‐step, one‐pot radiosynthesis of [18F]MK‐0518 via [18F]4‐fluorobenzylamine has been developed, giving sufficient quantities of [18F]MK‐0518 for animal positron emission tomography studies. Copyright © 2010 John Wiley & Sons, Ltd. A convenient three‐step, one‐pot radiosynthesis method for the HIV integrase inhibitor [18F]MK‐0518 via [ 18F]4‐fluorobenzylamine is described. This method included nucleophilic fluorination, nitrile reduction and coupling in the same reaction vial, giving sufficient quantities of [ 18F]MK‐0518 for in vivo PET studies, and is simple and convenient to use. Copyright © 2010 John Wiley & Sons, Ltd.