Fluorine-18-labeled 5-fluorouracil is a useful radiotracer for differentiation of malignant tumors from inflammatory lesions

Objective [F-18]-2-fluoro-2-deoxy-D-glucose ([F-18]-FDG) is a useful radiotracer to detect malignant tumors. However, inflammatory processes are likely to be mistaken as malignant tumors owing to strong accumulation of [F-18]-FDG. The fluorinated nucleoside base 5-fluorouracil has remained an important antimetabolite agent in the treatment of a variety of cancers. The objective of this study was to evaluate the possibility of discriminating between malignant tumors and inflammation by [F-18]-5-fluorouracil ([F-18]-5-FU). Methods [F-18]-5-FU was made with > 95% radiochemical purity in our laboratory. BALB/cAJcl-nu/nu mice were subcutaneously inoculated with colon carcinoma cell line, colon 26, into the left side of the back and turpentine oil into the right side of the back to cause chemical inflammation. We examined the biodistribution of [F-18]-5-FU in control mice and tumor-inflammation mice. We also examined the biodistribution of [F-18]-FDG as a baseline study. Approximately 1 MBq of either [F-18]-5-FU or [F-18]-FDG was injected into the tail vein of each mouse. The biodistribution study was performed at 1 and 2 h after injection. The radioactivity of each organ was measured by a gamma counter. Results [F-18]-5-FU uptakes in the liver and the kidney were especially high. Tumor-to-blood ratios were significantly higher at 2 h than at 1 h (3.69 +/- 0.40 vs. 1.81 +/- 0.37, P < 0.001). Tumor-to-inflammation ratios at 2 h following injection were significantly higher than those at 1 h (1.94 +/- 0.44 vs. 1.26 +/- 0.20, P < 0.001). At 2 h after radiotracer injection, the tumor-to-inflammation ratio of [F-18]-5-FU was significantly higher than that of [F-18]-FDG (1.94 +/- 0.44 vs. 1.03 +/- 0.23, P = 0.001). Conclusions Our data suggest that [F-18]-5-FU has a diagnostic potential as a positron emission tomography ligand for differentiating malignant tumors from inflammatory lesions.