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Journal of Nuclear Medicine Vol. 43 No. 12 1688-1698
© 2002 by Society of Nuclear Medicine


Basic Science Investigations

Rat Studies Comparing 11C-FMAU, 18F-FLT, and 76Br-BFU as Proliferation Markers

Li Lu, MD1,2, Linda Samuelsson, MSc3, Mats Bergström, PhD1, Kengo Sato, MSc1,4, Karl-Johan Fasth, PhD1 and Bengt Långström, PhD1,3

1 PET Center, Uppsala University Hospital, Uppsala, Sweden
2 Department of Pharmaceutics, Uppsala University, Uppsala, Sweden
3 Department of Organic Chemistry, Institute of Chemistry, Uppsala University, Uppsala, Sweden
4 Hamamatsu Photonics, Shizuoka, Japan

We analyzed and compared 1-(2'-deoxy-2'-fluoro-ß-D-arabinofuranosyl)-[methyl-11C]thymine (11C-FMAU), 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) and 1-(2'-deoxy-2'-fluoro-ß-D-arabinofuranosyl)-5-[76Br]bromouracil (76Br-BFU) with respect to tissue uptake, DNA incorporation, and excretion modulation in rats. The goal of the investigation was to evaluate the efficiency of the 3 nucleoside tracers as potential tracers for measuring proliferation. Methods: Sprague-Dawley rats were divided into 3 groups and administered 5 MBq 11C-FMAU, 1 MBq 18F-FLT, or 2 MBq 76Br-BFU. For each tracer, a subgroup was also administered 6 mg/kg cimetidine. The rats in the 11C-FMAU group were killed at 5, 20, 40, 60, and 80 min after injection; the rats in the 18F-FLT group were killed at 80 min and 2 and 4 h; and the rats in the 76Br-BFU group were killed at 5, 20, 40, and 80 min and 2, 4, 6, and 24 h. Samples of blood, liver, kidney, spleen, and intestine were taken, and the radioactivity was measured. DNA separation was made in the samples of spleen, and the radioactivity in the DNA fraction was measured. Results: Maximal uptake of radioactivity was seen in the spleen and intestine, organs with active DNA synthesis. The highest relative radioactivity uptake was at 60 min in the 11C-FMAU groups and at 4 h in the 18F-FLT group. In the 76Br-BFU group, the uptake increased gradually during the observation period, and uptake of radioactivity increased markedly in rats receiving cimetidine. Cimetidine did not affect radioactivity uptake in the 11C-FMAU or 18F-FLT groups. The fraction of radioactivity in DNA was 78% in spleen at 60 min in the 11C-FMAU group, 80% at 60 min and 97% at 4 h in the 76Br-BFU group. The DNA-incorporation was only 2% in the 18F-FLT group. Conclusion: 76Br-BFU predominantly incorporates into DNA and has great potential as a PET tracer for the assessment of proliferation in vivo. 11C-FMAU also may have potential as a proliferation marker, but the observation time is limited. 18F-FLT does not incorporate into DNA and is therefore not a direct marker of proliferation.

Key Words: PET • 11C-FMAU • 18F-FLT • 76Br-BFU • DNA synthesis




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