Biodistribution and radiation dosimetry estimates of 1-(2'-deoxy-2'-(18)F-Fluoro-1-beta-D-arabinofuranosyl)-5-bromouracil: PET imaging studies in dogs.
This study reports on the biodistribution and radiation estimates of 1-(2'-deoxy-2'-(18)F-fluoro-1-beta-d-arabinofuranosyl)-5-bromouracil ((18)F-FBAU), a potential tracer for imaging DNA synthesis.


METHODS
Three normal dogs were intravenously administered (18)F-FBAU and a dynamic PET scan was performed for 60 min over the upper abdomen followed by a whole-body scan for a total of 150 min. Blood samples were collected at stipulated time intervals to evaluate tracer clearance and metabolism. Tissue samples of various organs were analyzed for tracer uptake and DNA incorporation. Dynamic accumulation of the tracer in different organs was derived from reconstructed PET images. The radiation dosimetry of (18)F-FBAU was evaluated using the MIRD method.


RESULTS
At 60 min after injection, blood analysis found >90% of the activity in unmetabolized form. At 2 h after injection, (18)F-FBAU uptake was highest in proliferating tissues (mean SUVs: marrow, 2.6; small intestine, 4.0), whereas nonproliferative tissues showed little uptake (mean SUVs: muscle, 0.75; lung, 0.70; heart, 0.85; liver, 1.28). Dynamic image analysis over 60 min showed progressive uptake of the tracer in marrow. Extraction studies demonstrated that most of the activity in proliferative tissues was in the acid-insoluble fraction (marrow, 83%; small intestine, 73%), consistent with incorporation into DNA. In nonproliferative tissue, most of the activity was not found in the acid-insoluble fraction (>84% for heart, muscle, and liver).


CONCLUSIONS
These results demonstrate that (18)F-FBAU was resistant to metabolism, readily incorporated into DNA in proliferating tissues, and showed good contrast between organs of variable DNA synthesis. These findings indicate that (18)F-FBAU may find use in measuring DNA synthesis with PET.
Nimmagadda
Sridhar
S
Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48201-2013, USA.
Mangner
Thomas J
TJ
Sun
Haihao
H
Klecker
Raymond W
RW
Muzik
Otto
O
Lawhorn-Crews
Jawana M
JM
Douglas
Kirk A
KA
Collins
Jerry M
JM
Shields
Anthony F
AF
D000818:Animals; D001822:Body Burden; D001976:Bromouracil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004285:Dogs; D006801:Humans; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods*; D011829:Radiation Dosage; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012062:Relative Biological Effectiveness; D014018:Tissue Distribution; D051598:Whole Body Imaging; D014915:Whole-Body Counting
C470854:1-(2-fluoro-2-deoxyarabinofuranosyl)-5-bromouracil; D019275:Radiopharmaceuticals; D001976:Bromouracil