Evaluation of d-Isomers of O-11C-Methyl Tyrosine and O-18F-Fluoromethyl Tyrosine as Tumor-Imaging Agents in Tumor-Bearing Mice: Comparison with l- and d-11C-Methionine

摘要

id="p-1">The aim of this study was to investigate whether class="sc">d-amino acid isomers of O-11C-methyl tyrosine (11C-CMT) and O-18F-fluoromethyl tyrosine (18F-FMT) were better than the corresponding class="sc">l-isomers as tumor- detecting agents with PET in comparison with the difference between class="sc">l- and class="sc">d-methyl-11C-methionine (11C-MET). >Methods: class="sc">l- and class="sc">d-11C-MET, 11C-CMT, and 18F-FMT were injected intravenously into BALB/cA Jcl-nu mice bearing HeLa tumor cells. At 5, 15, 30, and 60 min after injection, normal abdominal organs and xenotransplanted HeLa cells were sampled, and the uptake of each ligand was determined. Metabolic analyses of these compounds in the plasma were also performed. Accumulation of the class="sc">d-isomers of 11C-MET, 11C-CMT, and 18F-FMT in turpentine-induced inflammatory tissue was assayed in comparison with 18F-FDG. The whole-body distribution of each tracer was imaged with a planar positron imaging system (PPIS). >Results: Although the tumor uptake (standardized uptake value [SUV]) levels of the class="sc">d-isomers of 11C-MET, 11C-CMT, and 18F-FMT were 261%, 72%, and 95% of each class="sc">l-isomer 60 min after administration, the tumor-to-blood ratios of these class="sc">d-isomers were 130%, 140%, and 182% of the corresponding class="sc">l-isomers. In the blood, the class="sc">d-isomers of these labeled compounds revealed a relatively faster elimination rate compared with their class="sc">l-isomers, with a high peak uptake in the blood and kidney 5 min after administration. Compared with the natural amino acid ligand class="sc">l-11C-MET, the uptake of class="sc">l-isomers of 11C-CMT and 18F-FMT was relatively low and stable in the abdominal organs, whereas class="sc">d-isomers revealed much lower levels and faster clearance rates compared with corresponding class="sc">l-isomers. Among the abdominal organs, the pancreas showed a relatively high uptake of 11C-CMT and 18F-FMT; the uptake of these class="sc">d-isomers was much lower than that of class="sc">l-isomers. Pretreatment with cycloheximide, a protein synthesis inhibitor, resulted in a marked reduction of class="sc">l-11C-MET uptake and a slight reduction of class="sc">d-11C-MET uptake into protein fractions, whereas no significant changes were detected with class="sc">l- and class="sc">d-11C-CMT and 18F-FMT. class="sc">d-Isomers of 11C-MET, 11C-CMT, and 18F-FMT did not accumulate in turpentine-induced inflammatory tissue, where 18F-FDG revealed a high uptake. Whole-body imaging with a PPIS provided consistent distribution data obtained from the tissue dissection analysis. >Conclusion: These results suggest that class="sc">d-isomers of 11C-CMT and 18F-FMT could be potentially better tracers than class="sc">l- and class="sc">d-11C-MET for tumor imaging with PET.