Concise and Scalable Radiosynthesis of (+)-[ 18 F]MDL100907 as a Serotonin 5-HT 2A Receptor Antagonist for PET.

5-Hydroxytryptamine (5-HT 2A ) receptors play an important role in several psychiatric disorders. In order to investigate the serotonin (5-HT) receptor in vivo , reliable syntheses are required for positron emission tomography (PET) 5-HT radioligands. Owing to the excellent in vivo properties of [ 18 F]MDL100907 for PET, there has been great interest to develop a novel synthetic route for [ 18 F]MDL100907. Here, we report a highly efficient, scalable, and expedient synthesis for [ 18 F]MDL100907. The radiofluorination was performed on a 18 F-labeling boron pinacol ester precursor, which is synthesized using the Liebeskind-Srogl cross-coupling reaction as a key step. Our method is practically more suitable to employ late-stage Cu-mediated radiofluorination and facilitate the production of the [ 18 F]MDL100907 radioligand in excellent decay-corrected RCY of 32 ± 10% ( n = 7) within 60 min. We prepared [ 18 F]MDL100907 in high molar activity (2.1 Ci/μmol) and compared it to [ 11 C]MDL100907 in the brain of a nonhuman primate.