A Practical Radiosynthesis of ( S )‐[ 11 C]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‐ 18 F‐fluoro‐2‐hydroxy)propoxy]quinoline (( S )‐[ 18 F]SMBT‐1), we developed a carbon‐11‐labeled analog, ( S )‐(2‐ 11 C‐methylpyrid‐5‐yl)‐6‐[(3‐fluoro‐2‐hydroxy)propoxy]quinoline (( S )‐[ 11 C]SMBT‐1). The short half‐life of carbon‐11 (t 1/2 = 20.7 min) enables same‐day, repeat scans and pharmacological challenge studies within the same subject. An efficient radiosynthesis of ( S )‐[ 11 C]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 )‐[ 11 C]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 )‐[ 11 C]SMBT‐1, and in vivo evaluation studies are currently underway to further assess its potential for future clinical MAO‐B PET imaging applications.