Revisiting the Radiosynthesis of [<sup>18</sup>F]FPEB and Preliminary PET Imaging in a Mouse Model of Alzheimer’s Disease
Cassis Varlow,
Emily Murrell,
Jason P. Holland,
Alina Kassenbrock,
Whitney Shannon,
Steven H. Liang,
Neil Vasdev,
Nickeisha A. Stephenson
Affiliations
Cassis Varlow
Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada
Emily Murrell
Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada
Jason P. Holland
Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA 02114, USA
Alina Kassenbrock
Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA 02114, USA
Whitney Shannon
Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada
Steven H. Liang
Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA 02114, USA
Neil Vasdev
Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada
Nickeisha A. Stephenson
Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada
[18F]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 [18F]FPEB has been an ongoing challenge. Herein, five metal-free precursors for the radiofluorination of [18F]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 [18F]FPEB in the highest RCYs of 25% and 36%, respectively. Preliminary PET/CT imaging studies with [18F]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.
