Universität zu Köln

Kraemer, Felicia, Groener, Benedikt, Hoffmann, Chris, Craig, Austin, Brugger, Melanie, Drzezga, Alexander, Timmer, Marco, Neumaier, Felix, Zlatopolskiy, Boris D., Endepols, Heike and Neumaier, Bernd (2021). Evaluation of 3-l- and 3-d-[F-18]Fluorophenylalanines as PET Tracers for Tumor Imaging. Cancers, 13 (23). BASEL: MDPI. ISSN 2072-6694

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Abstract

Simple Summary The early detection and treatment of malignant brain tumors can significantly improve the survival time and life quality of affected patients. Whereas positron emission tomography (PET) with O-(2-[F-18]fluoroethyl)tyrosine ([F-18]FET) offers improved diagnostic accuracy compared to other imaging methods, there is still a need for PET tracers with better tumor-specificity. A higher protein incorporation rate, as well as a higher affinity for the amino acid transporter LAT1, could provide probes with superior image quality compared to [F-18]FET. The aim of the present study was a preclinical evaluation of the two enantiomeric phenylalanine (Phe) analogues, 3-l- and 3-d-[F-18]fluorophenylalanine ([F-18]FPhes), as possible alternatives to [F-18]FET. Based on promising in vitro evaluation results, the radiolabeled amino acids were studied in vivo in two subcutaneous and one orthotopic rodent tumor xenograft models using mu PET. The results show that 3-l- and 3-d-[F-18]FPhe enable high-quality visualization of tumors with certain advantages over [F-18]FET, making them promising candidates for further preclinical and clinical evaluations. Purpose: The preclinical evaluation of 3-l- and 3-d-[F-18]FPhe in comparison to [F-18]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 mu PET 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 SUVmax, SUVmean and tumor-to-brain ratios (TBrR). Results: The uptake of 3-l-[F-18]FPhe in MCF-7 and PC-3 cells was significantly higher relative to [F-18]FET. The uptake of all three tracers was significantly reduced by the suppression of amino acid transport systems L or ASC. 3-l-[F-18]FPhe but not 3-d-[F-18]FPhe exhibited protein incorporation. In benserazide-treated healthy rats, brain uptake after 42-120 min was significantly higher for 3-d-[F-18]FPhe vs. 3-l-[F-18]FPhe. [F-18]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-[F-18]FPhe (SUVmax: 3-l-[F-18]FPhe, 107.6 +/- 11.3; 3-d-[F-18]FPhe, 86.0 +/- 4.3; [F-18]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 [F-18]FET.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kraemer, Felicia UNSPECIFIED UNSPECIFIED UNSPECIFIED Groener, Benedikt UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoffmann, Chris UNSPECIFIED UNSPECIFIED UNSPECIFIED Craig, Austin UNSPECIFIED UNSPECIFIED UNSPECIFIED Brugger, Melanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Drzezga, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Timmer, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Neumaier, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Zlatopolskiy, Boris D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Endepols, Heike UNSPECIFIED UNSPECIFIED UNSPECIFIED Neumaier, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-586769
DOI:	10.3390/cancers13236030
Journal or Publication Title:	Cancers
Volume:	13
Number:	23
Date:	2021
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2072-6694
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language AMINO-ACID TRANSPORTER; UPTAKE KINETICS; LAT1; GLIOMAS; CANCER; F-18-FLUORINATION; IDENTIFICATION; SYSTEM; ASCT2 Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58676