Radiosyntheses of labeled beta-pseudothymidine ([C-11]- and [H-3]methyl) and its biodistribution and metabolism in normal and tumored mice.
In order to develop labeled probes for measuring DNA synthetic rates in vivo we investigated [H-3]- and [C-11]methyl labeled beta-pseudothymidine (2a), and report on their radiosyntheses from methyl iodide. We find methylation is rapid and regioselective on N-1 of the acylurea moiety of 2'-deoxy-beta-D-pseudouridine (1a), in the presence of N,N-diisopropylethylamine and N,N-dimethylformamide at 60 degrees C. Although yields are low (11% [C-11]-decay corrected and 4.4% [H-3]), the method is simple and high specific activity tritiated methyl iodide can be used. In contrast to the rapid degradative de-glycosylation of thymidine in blood, beta-pseudothymidine is stable. However, based on biodistribution and metabolite studies, the anticipated uptake of [H-3]methyl-beta-pseudothymidine into mouse DNA of proliferating tissues (e.g. spleen, thymus and duodenum) and implanted tumors was not observed.
Grierson
J R
JR
Department of Radiology, University of Washington, Seattle, USA.
Shields
A F
AF
Zheng
M
M
Kozawa
S M
SM
Courter
J H
JH
D000818:Animals; D001711:Biotransformation; D002250:Carbon Radioisotopes; D017690:Cell Transplantation; D002851:Chromatography, High Pressure Liquid; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000096:biosynthesis; D007553:Isotope Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000378:metabolism*; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis; D013936:Thymidine / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014316:Tritium; D014407:Tumor Cells, Cultured
D002250:Carbon Radioisotopes; D015342:DNA Probes; D004273:DNA, Neoplasm; D011741:Pyrimidine Nucleosides; C096786:pseudothymidine; D014316:Tritium; D013936:Thymidine