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Biodistribution and Radiation Dosimetry Estimates of 1-(2'-Deoxy-2'-¹⁸F-Fluoro-1-ß-D-Arabinofuranosyl)-5-Bromouracil: PET Imaging Studies in Dogs

¹ Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
² Department of Medicine, Wayne State University, Detroit, Michigan
³ Department of Radiology, Wayne State University, Detroit, Michigan
⁴ Laboratory of Clinical Pharmacology, Food and Drug Administration, Rockville, Maryland
⁵ Department of Pediatrics, Wayne State University, Detroit, Michigan

This study reports on the biodistribution and radiation estimates of 1-(2'-deoxy-2'-¹⁸F-fluoro-1-ß-D-arabinofuranosyl)-5-bromouracil (¹⁸F-FBAU), a potential tracer for imaging DNA synthesis. Methods: Three normal dogs were intravenously administered ¹⁸F-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 ¹⁸F-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, ¹⁸F-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). Conclusion: These results demonstrate that ¹⁸F-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 ¹⁸F-FBAU may find use in measuring DNA synthesis with PET.

Key Words: ¹⁸F • FBAU • proliferation marker • DNA synthesis • metabolism

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