BIODISTRIBUTION STUDIES ON L-3-[FLUORINE-18]FLUORO-ALPHA-METHYL TYROSINE - A POTENTIAL TUMOR-DETECTING AGENT

Iodine-123-alpha-methyl tyrosine has proven to be a promising SPECT ag ent for imaging amino acid uptake in tumors. We developed L-[3-F-18]-a lpha-methyl tyrosine (FMT) for PET studies. The aim of this study was to investigate its potential use as a tumor-detecting agent by using t umor-bearing mice, Methods: We investigated the biodistribution in nor mal BALB/C mice and BALB/cA nude mice bearing human rectal cancer cell line (LS180) until 120 min postinjection. FMT tumor uptake at 60 min postinjection in mice with LS180 rectal cancer, RPMI1788 B-cell lympho ma and MCF7 mammary cell carcinoma was assessed, and the results were compared with F-18-fluoro-2-deoxy-D-glucose (FDG) tumor uptake. The ef fect of competitive inhibition of large neutral amino acid transport s ystem using unlabeled L-alanine was also investigated. Results: The am ount of FMT in blood fell to 1.05%ID/20 g at 60 min postinjectjon, whe reas that in the pancreas was 15.2%ID/20 g, resulting in a high pancre as-to-blood ratio of 14.5. In other organs, initial uptake peaked at 5 min postinjection and then declined with time. In LS180 tumor-bearing mice, peak FMT uptake in tumor was observed at 60 min postinjection. Tumor-to-blood and tumor-to-muscle ratios ranged from 1.60 to 2.94 and from 2.79 to 3.25 over the 120-min observation period. Tumor uptake o f FMT was clearly reduced by inhibition of the amino acid transport sy stem. In mice with LS180 and MCF7 tumors, FMT tumor uptake at 60 min p ostinjection was significantly higher than FDG tumor uptake, whereas i n RPMI1788 lymphoma, uptake of FDG was significantly higher than FMT t umor uptake, Tumor-to-blood ratios of FMT in mice with LS180, RPMI1788 and MCF7 tumor at 60 min postinjection were 1.82, 5.88 and 3.56, resp ectively. Conclusion: FMT, like other fluorinated amino acids, may bec ome a promising tumor-detecting agent for PET, assuming that efficient methods of radiosynthesis are developed.