Development of Biologically Active Nucleosides Labeled with Positron Emitting ^<18>F

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Metabolism of 2-deoxy-5-[^<18>F] fluorouridine (Fdurd), a useful positron emission tomography (PET) tracer of nucleic acid metabolism in tumors, was investigated in tumor-bearing mice and human plasma. Degradation of the tracer in vivo was very rapid. a-[^<18>F] Fluoro-b-alanine (FBAL) wasa main catabolite in the plasma. In tumor tissues, the activated derivatives of FdUrd, FBAL and the other catabolic materials were found; however, contribution of the plasma catabolites to the radioactivity accumulation in the tumor was minor. Nucleic acid metabolism in brain tumors by FdUrd-PET maybe assessed using normal brain regions as a reference.As new radiopharmaceuticals, 5-[^<75>Br] bromouracil (BrUra) and 5-[^<75>Br]bromo-2'-deoxyuridine (BrdUrd) were prepared from ^<75>Br anion and uracil or 2'-deoxyuridine by a chloramine-T method. The ^<75>Br was prepared by the ^<75>As(^3He,3n)^<75>Br reaction. In tumor-bearing rats given each of the tracer, radioactivity increased in tumor tissues. The level for BrdUrd was 2-times higher than that for BrUra. Although debromination was suggested in vivo, it is expected that the accumulation of the tracer in tumors may correlate with DNA synthesis in the t issue.As the other compounds, 5-[^<18>F] fluoro-2', 3'-isopropyridine-5'-0-(4-N-acetamide-2, 4-dideoxy-3, 6, 7, 8-tetra-0-acetyl-1-methoxycarbonyl-D-glycero-a-galacto-octapyranosyl) uridine was prepared using [^<18>F]AcOF or [^<18>F]F_2. But, animal studies of the compound was not done. Labeling of adenosine, guanosine and their derivatives using [^<18>F]AcOF and ^<18>F anion has been done unsuccessfully.