Abstract
1514
Objectives Amino acid anti-1-amino-2-[18F]fluoro-cyclobutyl-1-carboxylic acid (anti-2-[18F]FACBC) was synthesized and evaluated in vitro as potential PET tumor imaging agent in 5 human cancer cell lines.
Methods The precursor was prepared from 1,2-bis(trimethylsiloxy)cyclobtene, which was treated with benzyl alcohol to give 2-(benzyloxy)cyclobutanone. The intermediate, N-Boc-2-hydroxy amino acid t-butyl ester was prepared according to reported methods (Martarello L., et al, J. Med. Chem., 45, 2250, 2002). The alcohol was reacted with SOCl2 then NaIO4 to provide cyclic sulfamidate as labeling precursor. Radiolabeling was carried out with no-carrier-added [18F]KF-K222. Anti-2-[18F]FACBC was obtained by hydrolysis and chromatographic purification. The in vitro studies were performed in A549 (lung), SKOV3 (ovary), DU145 (prostate), MDA MB468 (breast) and U87 (brain) human cancer cell lines in Hank's Balanced Salt Solution incubated with tracer for 30 minutes at 37 C to evaluate the compound tumor cell uptake and transport mechanism. 10 mM BCH and 10 mM MeAIB were used as system L and A amino acid transport inhibitors, respectively. The cell uptake was calculated in percent initial dose per 0.5 million cells (%ID/5×105 cells).
Results Labeling yield was 30% (n=5) with radiochemical purity over 99% as measured by radiometric TLC. The results of cell assays were reported in the Table, with cell uptake from 4.2-8.3 %ID /5×105 cells. The inhibition of uptake by BCH was 29-77% vs. 10-87% by MeAIB.
Conclusions We found that anti-2- [18F]FACBC entered these tumor cells in vitro primarily via system L amino acid transport except for SKOV3 cells. The in vivo study will further validate this amino acid's property and the usefulness of tumor imaging with PET.
Research Support Research supported by Georgia Research Alliance and Georgia Cancer Coalition
Cell uptake of anti-2-[18F]FACBC (ID% /5×105 cells).
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