o-(2-fluoroethyl)tyrosine and Inflammation

The goal of this study was to compare the glucose analog, 2-[18F]fluoro-2-deoxy-d-glucose ([18F]-FDG), the amino acid analog, o-(2-[18F]fluoroethyl)-l-tyrosine ([18F]-FET) and nucleoside analog, 3'-[18F]fluoro-3'-deoxythymidine ([18F]-FLT) with regard to their feasibility for differentiating tumors from inflammation.. In Fisher rat models bearing both 9L tumor and inflammation, the biodistributions and positron emission tomography (PET) images of [18F]-FDG, [18F]-FET and [18F]-FLT at 60 min post injection were compared. Pretreatment with thymidine phosphorylase before injection of [18F]-FLT was performed.. The tumor-to-blood (T/B) and tumor-to-muscle (T/M) ratios of [18F]-FDG were significantly higher than those of [18F]-FET and [18F]-FLT (P<.01); however, the accumulation of [18F]-FDG [1.23+/-0.52 percent injected dose per gram of tissue (%ID/g)] in inflammation was also elevated. T/B and T/M ratios of [18F]-FET (2.3+/-0.5 and 2.2+/-0.5) were higher than those of [18F]-FLT (1.6+/-0.6 and 1.6+/-0.5), and inflammation uptake of those tracers was very low (0.63+/-0.19 and 0.27+/-0.16 %ID/g, respectively). [18F]-FET and [18F]-FLT showed higher selectivity indices (tumor-to-inflammation ratio corrected background) than [18F]-FDG. In PET images, [18F]-FDG was found to be accumulated in both tumor and inflammation, but [18F]-FET and [18F]-FLT selectively localized in tumor.. Our data confirm the result of previous studies that [18F]-FET and [18F]-FLT are superior to [18F]-FDG in differentiating tumor from inflammation.

Topics: Animals; Diagnosis, Differential; Dideoxynucleosides; Feasibility Studies; Female; Fluorodeoxyglucose F18; Inflammation; Neoplasms; Positron-Emission Tomography; Rats; Thymidine Phosphorylase; Tissue Distribution; Tyrosine

Previous studies suggest that radiolabelled amino acids could be superior to FDG in differentiating tumour and inflammation. Therefore the aim of this study was to investigate the uptake of FET and MET in human tumour and inflammatory cells and to investigate their uptake kinetics.. For uptake studies, cells were incubated with 370 kBq FET or 3.7 kBq MET for 15 min. Kinetic studies were performed at variable concentrations of FET and MET. Competitive inhibition studies were done with BCH, MeAIB and L: -serine.. All inflammatory cells incorporated more MET than the tumour cells. The uptake of FET, in contrast, was significantly lower in all inflammatory cells than in the tumour cells. In tumour cells the uptake of MET was about five times the uptake of FET. The competitive inhibitors reduced uptake of both tracers to 20-40% in tumour cells and to 70% in inflammatory cells. Kinetic studies showed that MET and FET transport was saturable in all cells except macrophages and followed a Michaelis-Menten kinetic. Highest capacity (V (max)) and affinity (K (m)) for the uptake of MET was observed in granulocytes. Capacity and affinity for FET uptake were highest in the DHL-4 cells.. In contrast to MET, FET accumulated to a significantly greater extent in tumour cells than in inflammatory cells. The marked differences between tumour and inflammatory cells concerning FET and MET uptake suggest that FET and MET are substrates of different subtypes of the L system.

Topics: Cells, Cultured; Colonic Neoplasms; Diagnosis, Differential; Fluorine Radioisotopes; Humans; Inflammation; Metabolic Clearance Rate; Methionine; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tyrosine

To develop S-(2-18F-fluoroethyl)-L-methionine (18FEMET) as an amino acid positron emission tomography (PET) tracer for tumors, and to evaluate the value of 18FEMET in the differentiation of experimental tumor and experimental inflammation.. 18FEMET was prepared by nucleophilic fluorination reaction via a two-step procedure. Biodistribution of 18FEMET in normal mice, carcinoma-bearing mice and inflammatory mice, and 18FEMET PET imaging for carcinoma-bearing mice and inflammatory mice were performed compared with 2-[18F] fluoro-2-deoxy-D-glucose (FDG) and O-(2-[18F] fluoroethyl)-L-tyrosine (FET).. The overall radiochemical yield with no decay correction was 15%-25%, the whole synthesis time was about 70 min by manual operation, and the radiochemical purity was above 95%. High uptake and long retention of 18FEMET in pancreas, kidney, colon, liver and heart were observed. But low uptakes in brain and blood were found. Furthermore, high uptake of 18FEMET, FDG and FET in tumor, high uptake of FDG in inflammatory tissue, and almost no uptake of 18FEMET and FET in inflammatory tissue were also observed.. 18FEMET is easy to prepare and can be used to differentiate between tumor and inflammatory tissue. It seems to be a potential amino acid tracer for tumors with PET imaging.

Topics: Animals; Fluorodeoxyglucose F18; Inflammation; Methionine; Mice; Neoplasm Transplantation; Radiopharmaceuticals; Sarcoma 180; Tissue Distribution; Tomography, Emission-Computed; Tumor Cells, Cultured; Tyrosine