Journal Article

FZJ-2024-03507

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Radiosynthesis and Preclinical Evaluation of m-[18F]FET and [18F]FET-OMe as Novel [18F]FET Analogs for Brain Tumor Imaging

Gröner, B.FZJ* ; Hoffmann, C.FZJ* ; Endepols, H.FZJ* ; Urusova, E.FZJ* ; Brugger, M.FZJ* ; Neumaier, F.FZJ* ; Timmer, M. ; Neumaier, B. (Corresponding author)FZJ* ; Zlatopolskiy, B. D.

2024
American Chemical Society Washington, DC

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Please use a persistent id in citations: doi:10.1021/acs.molpharmaceut.3c01215  doi:10.34734/FZJ-2024-03507

Abstract: O-([18F]Fluoroethyl)-L-tyrosine ([18F]FET) is activelytransported into the brain and cancer cells by LAT1 andpossibly other amino acid transporters, which enables brain tumorimaging by positron emission tomography (PET). However, tumordelivery of this probe in the presence of competing amino acidsmay be limited by a relatively low affinity for LAT1. The aim of thepresent work was to evaluate the meta-substituted [18F]FET analogm-[18F]FET and the methyl ester [18F]FET-OMe, which weredesigned to improve tumor delivery by altering the physicochemical,pharmacokinetic, and/or transport properties. Both tracerscould be prepared with good radiochemical yields of 41−56%within 66−90 min. Preclinical evaluation with [18F]FET as areference tracer demonstrated reduced in vitro uptake of [18F]FETOMeby U87 glioblastoma cells and no advantage for in vivo tumor imaging. In contrast, m-[18F]FET showed significantly improvedin vitro uptake and accelerated in vivo tumor accumulation in an orthotopic glioblastoma model. As such, our work identifies m-[18F]FET as a promising alternative to [18F]FET for brain tumor imaging that deserves further evaluation with regard to its transportproperties and in vivo biodistribution.

Note: This work was supported, in part, by DeutscheForschungsgemeinschaft (DFG) grants ZL 65/1-1, ZL 65/3-1,and ZL 65/4-1.

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Contributing Institute(s):

1. Nuklearchemie (INM-5)

Research Program(s):

1. 5253 - Neuroimaging (POF4-525) (POF4-525)

Appears in the scientific report 2024

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