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

• Published in: ACS chemical neuroscience 2023-10, Vol.14 (19), p.3694-3703
• Main Authors: Chavan, Lahu N, Voll, Ronald, Sanchez, Mar M, Nye, Jonathon A, Goodman, Mark M
• Format: Article
• Language: English
• Subjects: Animals; Brain - diagnostic imaging; Fluorine Radioisotopes; Humans; Piperidines; Positron-Emission Tomography - methods; Radiopharmaceuticals; Receptor, Serotonin, 5-HT2A; Receptors, Serotonin; Serotonin
• ISSN: 1948-7193; 1948-7193
• DOI: 10.1021/acschemneuro.3c00382

5-Hydroxytryptamine (5-HT ) receptors play an important role in several psychiatric disorders. In order to investigate the serotonin (5-HT) receptor , reliable syntheses are required for positron emission tomography (PET) 5-HT radioligands. Owing to the excellent properties of [ F]MDL100907 for PET, there has been great interest to develop a novel synthetic route for [ F]MDL100907. Here, we report a highly efficient, scalable, and expedient synthesis for [ F]MDL100907. The radiofluorination was performed on a 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 [ F]MDL100907 radioligand in excellent decay-corrected RCY of 32 ± 10% ( = 7) within 60 min. We prepared [ F]MDL100907 in high molar activity (2.1 Ci/μmol) and compared it to [ C]MDL100907 in the brain of a nonhuman primate.