TY - JOUR T1 - Evaluation of <span class="sc">d</span>-Isomers of <em>O</em>-<sup>11</sup>C-Methyl Tyrosine and <em>O</em>-<sup>18</sup>F-Fluoromethyl Tyrosine as Tumor-Imaging Agents in Tumor-Bearing Mice: Comparison with <span class="sc">l</span>- and <span class="sc">d</span>-<sup>11</sup>C-Methionine JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 679 LP - 688 VL - 47 IS - 4 AU - Hideo Tsukada AU - Kengo Sato AU - Dai Fukumoto AU - Shingo Nishiyama AU - Norihiro Harada AU - Takeharu Kakiuchi Y1 - 2006/04/01 UR - http://jnm.snmjournals.org/content/47/4/679.abstract N2 - The aim of this study was to investigate whether d-amino acid isomers of O-11C-methyl tyrosine (11C-CMT) and O-18F-fluoromethyl tyrosine (18F-FMT) were better than the corresponding l-isomers as tumor- detecting agents with PET in comparison with the difference between l- and d-methyl-11C-methionine (11C-MET). Methods: l- and 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 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 d-isomers of 11C-MET, 11C-CMT, and 18F-FMT were 261%, 72%, and 95% of each l-isomer 60 min after administration, the tumor-to-blood ratios of these d-isomers were 130%, 140%, and 182% of the corresponding l-isomers. In the blood, the d-isomers of these labeled compounds revealed a relatively faster elimination rate compared with their l-isomers, with a high peak uptake in the blood and kidney 5 min after administration. Compared with the natural amino acid ligand l-11C-MET, the uptake of l-isomers of 11C-CMT and 18F-FMT was relatively low and stable in the abdominal organs, whereas d-isomers revealed much lower levels and faster clearance rates compared with corresponding l-isomers. Among the abdominal organs, the pancreas showed a relatively high uptake of 11C-CMT and 18F-FMT; the uptake of these d-isomers was much lower than that of l-isomers. Pretreatment with cycloheximide, a protein synthesis inhibitor, resulted in a marked reduction of l-11C-MET uptake and a slight reduction of d-11C-MET uptake into protein fractions, whereas no significant changes were detected with l- and d-11C-CMT and 18F-FMT. 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 d-isomers of 11C-CMT and 18F-FMT could be potentially better tracers than l- and d-11C-MET for tumor imaging with PET. ER -