Revisiting the Radiosynthesis of [18F]FPEB and Preliminary PET Imaging in a Mouse Model of Alzheimer’s Disease
by
Cassis Varlow 1,2
, Emily Murrell 1, Jason P. Holland 3,4, Alina Kassenbrock 3, Whitney Shannon 1,5, Steven H. Liang 3, Neil Vasdev 1,3,6,* and Nickeisha A. Stephenson 1,3,7,*
Cassis Varlow 1,2, Emily Murrell 1, Jason P. Holland 3,4, Alina Kassenbrock 3, Whitney Shannon 1,5, Steven H. Liang 3, Neil Vasdev 1,3,6,* and Nickeisha A. Stephenson 1,3,7,*
1
Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada
2
Institute of Medical Science, University of Toronto, Toronto, ON M5S1A8, Canada
3
Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA 02114, USA
4
Department of Chemistry, University of Zurich, 8057 Zurich, Switzerland
5
Department of Chemistry, University of Saskatchewan, Saskatoon, SK S7N OX2, Canada
6
Department of Psychiatry, University of Toronto, Toronto, ON M5T-1R8, Canada
7
Department of Chemistry, The University of West Indies at Mona, Kingston 7, Jamaica
*
Authors to whom correspondence should be addressed.
Academic Editor: Svend Borup Jensen
Molecules 2020, 25(4), 982; https://doi.org/10.3390/molecules25040982
Received: 30 January 2020 / Revised: 19 February 2020 / Accepted: 20 February 2020 / Published: 22 February 2020
(This article belongs to the Special Issue Past, Present, and Future of Radiochemical Synthesis)
[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.
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Keywords:
[18F]FPEB; mGluR5; positron emission tomography (PET); iodonium-ylide; Alzheimer’s Disease (AD)
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MDPI and ACS Style
Varlow, C.; Murrell, E.; Holland, J.P.; Kassenbrock, A.; Shannon, W.; Liang, S.H.; Vasdev, N.; Stephenson, N.A. Revisiting the Radiosynthesis of [18F]FPEB and Preliminary PET Imaging in a Mouse Model of Alzheimer’s Disease. Molecules 2020, 25, 982.
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