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. 2020 Feb 22;25(4):982.
doi: 10.3390/molecules25040982.

Revisiting the Radiosynthesis of [18F]FPEB and Preliminary PET Imaging in a Mouse Model of Alzheimer's Disease

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 , Nickeisha A Stephenson  1   3   7
Affiliations

Revisiting the Radiosynthesis of [18F]FPEB and Preliminary PET Imaging in a Mouse Model of Alzheimer's Disease

Cassis Varlow et al. Molecules. .

Abstract

[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.

Keywords: Alzheimer’s Disease (AD); [18F]FPEB; iodonium-ylide; mGluR5; positron emission tomography (PET).

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Conflict of interest statement

N.A.S., S.H.L. and N.V. have an issued patent entitled, “Iodine(III)-Mediated Radiofluorination; US 9.434,699 B2, that is licensed to a third party; S.H.L. and N.V. have a patent entitled, “Method of Fluorination Using Iodonium Ylides, US 9.434,699 B2. The authors declare no other conflicts of interest.

Figures

Figure 1
Figure 1
(A) PET/CT images of [18F]FPEB 20 min post-injection in 10 month old APP/PS1 (transgenic) mice and aged-matched wild-type (WT) B6C3F1/J (control) mice, n = 3/group. (B) Time–activity curve for whole-brain. (C) Mean area under the curve (AUC).
See this image and copyright information in PMC

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