Development of labeled thymidine analogs for imaging tumor proliferation.
We have sought nucleoside analogs suitable for labeling with F-18 that could be used to image tumor proliferation with positron emission tomography (PET). The following three thymidine analogs were labeled with tritium and screened for their catabolism and biodistribution in vivo in mice: 5-fluoro-1-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl)uracil (FFUdR), 5-fluoro-1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-uracil (FFaraU) and 5-methyl-1-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl)uracil (FTdR). We found that all three compounds were stable to degradation in vivo and when incubated in blood. Of the three analogs tested, only FFUdR showed preferential retention in rapidly proliferating tissues, such as the spleen and implanted tumors, and it attained tissue to blood ratios of 2.1 at 2 h.
Shields
A F
AF
Department of Medicine, University of Washington, Seattle, USA.
Grierson
J R
JR
Kozawa
S M
SM
Zheng
M
M
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000493:pharmacokinetics; D001086:Arabinofuranosyluracil / Q000737:chemistry / Q000493:pharmacokinetics; D001711:Biotransformation; D004285:Dogs; D005467:Floxuridine / Q000737:chemistry / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes; D066298:In Vitro Techniques; D007553:Isotope Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging*; D013936:Thymidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D000964:Antimetabolites, Antineoplastic; D005462:Fluorine Radioisotopes; D005467:Floxuridine; C068636:2'-fluorothymidine; D001086:Arabinofuranosyluracil; D013936:Thymidine