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COMPARATIVE STUDY
JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Rat studies comparing 11C-FMAU, 18F-FLT, and 76Br-BFU as proliferation markers.
Journal of Nuclear Medicine 2002 December
UNLABELLED: We analyzed and compared 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-[methyl-(11)C]thymine ((11)C-FMAU), 3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) and 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-[(76)Br]bromouracil ((76)Br-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 (11)C-FMAU, 1 MBq (18)F-FLT, or 2 MBq (76)Br-BFU. For each tracer, a subgroup was also administered 6 mg/kg cimetidine. The rats in the (11)C-FMAU group were killed at 5, 20, 40, 60, and 80 min after injection; the rats in the (18)F-FLT group were killed at 80 min and 2 and 4 h; and the rats in the (76)Br-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 (11)C-FMAU groups and at 4 h in the (18)F-FLT group. In the (76)Br-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 (11)C-FMAU or (18)F-FLT groups. The fraction of radioactivity in DNA was 78% in spleen at 60 min in the (11)C-FMAU group, 80% at 60 min and 97% at 4 h in the (76)Br-BFU group. The DNA-incorporation was only 2% in the (18)F-FLT group.
CONCLUSION: (76)Br-BFU predominantly incorporates into DNA and has great potential as a PET tracer for the assessment of proliferation in vivo. (11)C-FMAU also may have potential as a proliferation marker, but the observation time is limited. (18)F-FLT does not incorporate into DNA and is therefore not a direct marker of proliferation.
METHODS: Sprague-Dawley rats were divided into 3 groups and administered 5 MBq (11)C-FMAU, 1 MBq (18)F-FLT, or 2 MBq (76)Br-BFU. For each tracer, a subgroup was also administered 6 mg/kg cimetidine. The rats in the (11)C-FMAU group were killed at 5, 20, 40, 60, and 80 min after injection; the rats in the (18)F-FLT group were killed at 80 min and 2 and 4 h; and the rats in the (76)Br-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 (11)C-FMAU groups and at 4 h in the (18)F-FLT group. In the (76)Br-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 (11)C-FMAU or (18)F-FLT groups. The fraction of radioactivity in DNA was 78% in spleen at 60 min in the (11)C-FMAU group, 80% at 60 min and 97% at 4 h in the (76)Br-BFU group. The DNA-incorporation was only 2% in the (18)F-FLT group.
CONCLUSION: (76)Br-BFU predominantly incorporates into DNA and has great potential as a PET tracer for the assessment of proliferation in vivo. (11)C-FMAU also may have potential as a proliferation marker, but the observation time is limited. (18)F-FLT does not incorporate into DNA and is therefore not a direct marker of proliferation.
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