Radiosynthesis, in vitro and preliminary biological evaluation of [18F]2 ‐amino‐4‐((2‐((3‐fluorobenzyl)oxy)benzyl)(2‐((3‐(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid, a novel alanine serine cysteine transporter 2 inhibitor‐based positron emission tomography tracer

We have successfully synthesized [18F]FABAAB, the first fluorine ‐18 labeled derivative of compound V‐9302 with an overall nondecay corrected yield of 3.66 ± 1.90%. in vitro experiments show Ki values of 90 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. 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‐labeled version of a V‐9302 analogue, on e of the most potent inhibitors of ASCT‐2. The precursor was labeled with fluorine‐18 via a nucleophilic substitution of the corresponding benzylic bromide. The cold reference product was subjected to in vitro assays with [3H]glutamine in a PC ‐3 and F98 cell line to determine the affinity for both the human and rat ASCT‐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 nondecay corrected yield of 3.66 ± 1.90%. in vit ro experiments show inhibitor constantsKi of 90 and 125 μM for the PC‐3 and F9...
Source: Journal of Labelled Compounds and Radiopharmaceuticals - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research