Evaluation of [76Br]FBAU 3',5'-dibenzoate as a lipophilic prodrug for brain imaging.
[76Br]FBAU is a potential PET tracer for assessing proliferation. This study proposes that [76Br]FBAU 3',5'-dibenzoate has higher blood-brain-barrier permeability than [76Br]FBAU itself and thus might be better suited for applications in the brain. The brain uptake indexes of the two compounds measured after carotid injection (29.6 +/- 13.9 for [76Br]FBAU 3',5'-dibenzoate, versus 10.0 +/- 8.7 for [76Br]FBAU) support this claim. Biodistribution study also showed that the brain accumulation of activity was higher in rats injected with [76Br]FBAU 3',5'-dibenzoate than with [76Br]FBAU (0.119+/-0.023 DUR at 1 h, versus 0.061 +/- 0.006). [76Br]FBAU 3',5'-dibenzoate was relatively stable in rat plasma, gradually being hydrolyzed to [76Br]FBAU exponentially with a calculated half-life of 0.8 h. DNA incorporation of [76Br]FBAU was also confirmed. The results presented support the hypothesis that the 3',5'-dibenzoate can act as a prodrug for FBAU and deliver more radiolabeled nucleoside to the brain.
Kao
Chih-Hao K
CH
Positron Emission Tomography Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. ck123j@nih.gov
Waki
Atsuo
A
Sassaman
Mark B
MB
Jagoda
Elaine M
EM
Szajek
Lawrence P
LP
Ravasi
Laura
L
Shimoji
Kazuaki
K
Eckelman
William C
WC
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001976:Bromouracil / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D004247:DNA / Q000378:metabolism; D005260:Female; D006868:Hydrolysis; D008297:Male; D008956:Models, Chemical; D008958:Models, Molecular; D011355:Prodrugs / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
C470853:1-(2-fluoro-2-deoxy-3,5-O-dibenzoylarabinofuranosyl)-5-bromouracil; C470854:1-(2-fluoro-2-deoxyarabinofuranosyl)-5-bromouracil; D011355:Prodrugs; D019275:Radiopharmaceuticals; D001976:Bromouracil; D004247:DNA