Artikel
Evaluation of 3-L- and 3-D-[18F] Fluorophenylalanines as PET tracers for tumour imaging
Evaluierung von 3-L- and 3-D-[18F] Fluorophenylalanine als PET Tracers zum Imaging von Tumoren
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Veröffentlicht: | 25. Mai 2022 |
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Gliederung
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Objective: Early detection and treatment of malignant brain tumors can significantly improve survival time and life quality of affected patients. While positron emission tomography (PET) with O-(2-[18F]fluoroethyl)tyrosin ([18F]FET) offers improved diagnostic accuracy in comparison to other imaging methods, there is still a need for PET-tracers with greater tumor-specificity. Higher protein incorporation rate as well as higher affinity for the amino acid transporter LAT1 could provide probes with superior image quality compared to [18F]FET. Aim of the present study was the preclinical evaluation of two enantiomeric phenylalanine (Phe) analogues (3-l- and 3-d-[18F]fluorophenylalanine (FPhe) as possible alternatives to [18F]FET.
Methods: In vitro studies were conducted with MCF-7, PC-3 and U87 MG human tumor cell lines. In vivo µPET studies were carried out in healthy rats with/without benserazide pre-treatment (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 SUVmax, SUVmean and tumor-to-brain ratios (TBrR).
Results: Uptake of 3-l-[18F]FPhe in MCF-7 and PC-3 cells was significantly higher than with [18F]FET. Uptake of all three tracers was significantly reduced by 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 (SUVmax: 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 clear tumor delineation with an imaging quality comparable to [18F]FET.
Conclusion: The results show that 3-l- and 3-d-[18F]FPhe enable high quality visualization of tumor tissues with certain advantages over [18F]FET, making them promising candidates for further preclinical and clinical evaluations.