TY  - JOUR
AU  - Gröner, Benedikt
AU  - Hoffmann, Chris
AU  - Endepols, Heike
AU  - Urusova, Elizaveta
AU  - Brugger, Melanie
AU  - Neumaier, Felix
AU  - Timmer, Marco
AU  - Neumaier, Bernd
AU  - Zlatopolskiy, Boris D.
TI  - Radiosynthesis and Preclinical Evaluation of m-[18F]FET and [18F]FET-OMe as Novel [18F]FET Analogs for Brain Tumor Imaging
JO  - Molecular pharmaceutics
VL  - 21
SN  - 1543-8384
CY  - Washington, DC
PB  - American Chemical Society
M1  - FZJ-2024-03507
SP  - 2795-2812
PY  - 2024
N1  - This work was supported, in part, by DeutscheForschungsgemeinschaft (DFG) grants ZL 65/1-1, ZL 65/3-1,and ZL 65/4-1.
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 38747353
UR  - <Go to ISI:>//WOS:001225916700001
DO  - DOI:10.1021/acs.molpharmaceut.3c01215
UR  - https://juser.fz-juelich.de/record/1026693
ER  -