SYNTHESIS OF RO-5-[C-11]-METHYL-1-BETA-D-ARABINOFURANOSYLURACIL ([C-11]-FMAU) - A POTENTIAL NUCLEOSIDE ANALOG FOR IN-VIVO STUDY OF CELLULARPROLIFERATION WITH PET

Rapid in vivo catabolism limits the use of currently available radiotr acers used in tumor proliferation studies with PET. This is manifested by the need to develop complex mathematical models to interpret kinet ic and metabolite data obtained from imaging studies with agents such as carbon-11 labeled thymidine. A potential carbon-11 labeled radiotra cer for cellular proliferation, -5-([C-11]-methyl)-1-beta-D-arabinofur anosyluracil (FMAU), has been prepared using a previously described me thod for preparation of [C-11]methyl-thymidine where selective alkylat ion of a pyrimidyl dianion is accomplished with [C-11]methyl iodide at the 5-position of the pyrimidine ring. FMAU shares many in vivo chara cteristics of thymidine, including cellular transport, phosphorylation by mammalian kinase, and incorporation into DNA. Most importantly, in vivo catabolism of FMAU is limited, potentially yielding simplified k inetic models for determination of cellular proliferation with positro n emission tomography.