Development of new [18F]FET analogs for brain tumor imaging

Abstract

O-([¹⁸F]Fluoroethyl)-l-tyrosine ([¹⁸F]FET) is a clinically established radiotracer for PET imaging of brain tumors, but its tumor uptake is limited by a relatively low affinity for its biological target LAT1. To identify radiotracers with improved affinity and tumor uptake, the meta-substituted [¹⁸F]FET analog m-[¹⁸F]FET and the methyl ester [¹⁸F]FET-OMe were developed and compared to [¹⁸F]FET. The results showed reduced in vitro uptake of [¹⁸F]FET-OMe by tumor cells and no advantages for in vivo imaging in a brain tumor model. In contrast, m-[¹⁸F]FET exhibited significantly improved in vitro uptake and accelerated in vivo tumor accumulation. As such, m-[¹⁸F]FET represents a promising alternative to [¹⁸F]FET for brain tumor imaging.

Gröner, B.; Hoffmann, C.; Endepols, H.; Urusova, E.; Brugger, M.; Neumaier, F.; Timmer, M.; Neumaier, B.; Zlatopolskiy, B. D.

Radiosynthesis and Preclinical Evaluation of m-[¹⁸F]FET and [¹⁸F]FET-OMe as Novel [¹⁸F]FET Analogs for Brain Tumor Imaging

Molecular pharmaceutics 2024, 21, 2795-2812.