Development of labeled thymidine analogs for imaging tumor proliferation.

Abstract

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.

• Authors: A F Shields, J R Grierson, S M Kozawa, M Zheng
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 23 Issue 1 Pg. 17-22 (Jan 1996) ISSN: 0969-8051 [Print] United States
• PMID: 9004909 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antimetabolites, Antineoplastic
• Fluorine Radioisotopes
• Floxuridine
• 2'-fluorothymidine
• Arabinofuranosyluracil
• Thymidine

Topics

• Animals
• Antimetabolites, Antineoplastic (chemistry, pharmacokinetics)
• Arabinofuranosyluracil (chemistry, pharmacokinetics)
• Biotransformation
• Dogs
• Floxuridine (chemistry, pharmacokinetics)
• Fluorine Radioisotopes
• In Vitro Techniques
• Isotope Labeling
• Mice
• Mice, Inbred BALB C
• Neoplasm Transplantation
• Neoplasms, Experimental (diagnostic imaging)
• Thymidine (analogs & derivatives, chemistry, pharmacokinetics)
• Tissue Distribution
• Tomography, Emission-Computed