The metabolic alterations in tumors make it possible to visualize the latter by means of positron emission tomography, enabling diagnosis and providing metabolic information. The alanine serine cysteine transporter-2 (ASCT-2) is the main transporter of glutamine and is upregulated in several tumors. Therefore, a good positron emission tracer targeting this transport protein would have substantial value. Hence, the aim of this study is to develop a fluorine-18 labelled version of a V-9302 analogue, one of the most potent inhibitors of ASCT-2.
The precursor was labelled with fluorine-18 via a nucleophilic substitution of the corresponding benzylic bromide. The cold reference product was subjected to in vitro assays with [ H]glutamine in a PC-3 and F98 cell line to determine the affinity for both the human and rat alanine serine cysteine transporter-2. To evaluate the tracer potential dynamic μPET images were acquired in a mouse xenograft model for prostate cancer.
The tracer could be synthesized with an overall non-decay corrected yield of 3.66 ± 1.90 %. In vitro experiments show inhibitor constants K of 90 μM and 125 μM for the PC-3 and F98 cells, respectively. The experiments in the PC-3 xenograft demonstrate a low uptake in the tumor tissue.
We have successfully synthesized the radiotracer [ F]2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid. In vitro experiments show a good affinity for both the human and rat ASCT-2. However, the tracer suffers from poor in vivo tumor uptake in the PC-3 model. Briefly, we present the first fluorine-18 labelled derivative of compound V-9302, a promising novel ASCT-2 blocker used for inhibition of tumor growth.
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