Evaluation of 3-l- and 3-d-[18F]Fluorophenylalanines as PET Tracers for Tumor Imaging

Cancers

Marco Timmer¹  Alexander Drzezga²  Chris Hoffmann³  Felix Neumaier³  Benedikt Gröner³  Austin Craig³  Boris D. Zlatopolskiy³  Heike Endepols³  Bernd Neumaier³  Felicia Krämer³  Melanie Brugger⁴ 

[1] Center for Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany;Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany;Institute of Radiochemistry and Experimental Molecular Imaging, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany;Nuclear Chemistry (INM-5), Institute of Neuroscience and Medicine, Forschungszentrum Jülich GmbH, Wilhelm-Johnen-Straße, 52428 Jülich, Germany;

关键词: PET;    nuclear medicine;    radiotracer;    orthotopic xenograft model;    [¹⁸F]FPhe;    glioblastoma;   

DOI  :  10.3390/cancers13236030

来源: DOAJ

【 摘 要 】

Purpose: The preclinical evaluation of 3-l- and 3-d-[¹⁸F]FPhe in comparison to [¹⁸F]FET, an established tracer for tumor imaging. Methods: In vitro studies were conducted with MCF-7, PC-3, and U87 MG human tumor cell lines. In vivo µPET studies were conducted in healthy rats with/without the inhibition of peripheral aromatic l-amino acid decarboxylase by benserazide pretreatment (n = 3 each), in mice bearing subcutaneous MCF-7 or PC-3 tumor xenografts (n = 10), and in rats bearing orthotopic U87 MG tumor xenografts (n = 14). Tracer accumulation was quantified by SUV_max, SUV_mean and tumor-to-brain ratios (TBrR). Results: The uptake of 3-l-[¹⁸F]FPhe in MCF-7 and PC-3 cells was significantly higher relative to [¹⁸F]FET. The uptake of all three tracers was significantly reduced by the suppression of amino acid transport systems L or ASC. 3-l-[¹⁸F]FPhe but not 3-d-[¹⁸F]FPhe exhibited protein incorporation. In benserazide-treated healthy rats, brain uptake after 42–120 min was significantly higher for 3-d-[¹⁸F]FPhe vs. 3-l-[¹⁸F]FPhe. [¹⁸F]FET showed significantly higher uptake into subcutaneous MCF-7 tumors (52–60 min p.i.), while early uptake into orthotopic U87 MG tumors was significantly higher for 3-l-[¹⁸F]FPhe (SUV_max: 3-l-[¹⁸F]FPhe, 107.6 ± 11.3; 3-d-[¹⁸F]FPhe, 86.0 ± 4.3; [¹⁸F]FET, 90.2 ± 7.7). Increased tumoral expression of LAT1 and ASCT2 was confirmed immunohistologically. Conclusion: Both novel tracers enable accurate tumor delineation with an imaging quality comparable to [¹⁸F]FET.

【 授权许可】

Unknown