Varlow Cassis, Murrell Emily, Holland Jason P, Kassenbrock Alina, Shannon Whitney, Liang Steven H, Vasdev Neil, Stephenson Nickeisha A
Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada.
Institute of Medical Science, University of Toronto, Toronto, ON M5S1A8, Canada.
Molecules. 2020 Feb 22;25(4):982. doi: 10.3390/molecules25040982.
[F]FPEB is a positron emission tomography (PET) radiopharmaceutical used for imaging the abundance and distribution of mGluR5 in the central nervous system (CNS). Efficient radiolabeling of the aromatic ring of [F]FPEB has been an ongoing challenge. Herein, five metal-free precursors for the radiofluorination of [F]FPEB were compared, namely, a chloro-, nitro-, sulfonium salt, and two spirocyclic iodonium ylide (SCIDY) precursors bearing a cyclopentyl (SPI5) and a new adamantyl (SPIAd) auxiliary. The chloro- and nitro-precursors resulted in a low radiochemical yield (<10% RCY), whereas both SCIDY precursors and the sulfonium salt precursor produced [F]FPEB in the highest RCYs of 25% and 36%, respectively. Preliminary PET/CT imaging studies with [F]FPEB were conducted in a transgenic model of Alzheimer's Disease (AD) using B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J (APP/PS1) mice, and data were compared with age-matched wild-type (WT) B6C3F1/J control mice. In APP/PS1 mice, whole brain distribution at 5 min post-injection showed a slightly higher uptake (SUV = 4.8 ± 0.4) than in age-matched controls (SUV = 4.0 ± 0.2). Further studies to explore mGluR5 as an early biomarker for AD are underway.
[F]FPEB是一种正电子发射断层扫描（PET）放射性药物，用于成像中枢神经系统（CNS）中代谢型谷氨酸受体5（mGluR5）的丰度和分布。[F]FPEB芳环的高效放射性标记一直是一个持续存在的挑战。在此，比较了用于[F]FPEB放射性氟化的五种无金属前体，即氯代、硝基、锍盐以及两种带有环戊基（SPI5）和新型金刚烷基（SPIAd）辅助基团的螺环碘鎓叶立德（SCIDY）前体。氯代和硝基前体的放射化学产率较低（<10% RCY），而两种SCIDY前体和锍盐前体分别以25%和36%的最高RCY产生了[F]FPEB。使用B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J（APP/PS1）小鼠在阿尔茨海默病（AD）转基因模型中进行了[F]FPEB的初步PET/CT成像研究，并将数据与年龄匹配的野生型（WT）B6C3F1/J对照小鼠进行了比较。在APP/PS1小鼠中，注射后5分钟时全脑分布显示摄取略高于年龄匹配的对照组（SUV = 4.8 ± 0.4）（SUV = 4.0 ± 0.2）。正在进行进一步研究以探索mGluR5作为AD早期生物标志物的作用。
