A Practical Radiosynthesis of (S)-[11C]SMBT-1 for MAO-B PET Imaging.

Monoamine oxidase B (MAO-B) is highly expressed in reactive astrocytes and is implicated in multiple neurodegenerative and neuropsychiatric conditions, making it an important PET imaging target. Building on the promising PET imaging properties of (S)-(2-methylpyrid-5-yl)-6-[(3-18F-fluoro-2-hydroxy)propoxy]quinoline ((S)-[18F]SMBT-1), we developed a carbon-11-labeled analog, (S)-(2-11C-methylpyrid-5-yl)-6-[(3-fluoro-2-hydroxy)propoxy]quinoline ((S)-[11C]SMBT-1). The short half-life of carbon-11 (t1/2 = 20.7 min) enables same-day, repeat scans and pharmacological challenge studies within the same subject. An efficient radiosynthesis of (S)-[11C]SMBT-1 was developed via palladium-mediated Stille cross-coupling followed by acid deprotection. The radiosynthesis was completed within 28.4 ± 0.9 min from end of bombardment (EOB) (n = 3), providing (S)-[11C]SMBT-1 in 11.9% ± 2.7% radiochemical yield (decay-corrected) with final product activity of 1.76 ± 0.28 GBq (47.4 ± 7.5 mCi) and molar activity of 58.8 ± 8.0 GBq/μmol (1.59 ± 0.22 Ci/μmol) at end of synthesis (EOS), high radiochemical purity (> 99%) and enantiomeric excess (> 99%). The developed radiosynthetic method provides reliable access to (S)-[11C]SMBT-1, and in vivo evaluation studies are currently underway to further assess its potential for future clinical MAO-B PET imaging applications.