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Imaging DNA Synthesis In Vivo with 18F-FMAU and PET

Haihao Sun, MD, PhD1,2, Thomas J. Mangner, PhD2,3, Jerry M. Collins, PhD4, Otto Muzik, PhD2,5, Kirk Douglas, MS1,2 and Anthony F. Shields, MD, PhD1,2

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



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  		FIGURE 1. Attenuation-corrected projection (A) and sagittal (B) PET images of a dog 68–150 min after injection of 81.4 MBq of 18F-FMAU show accumulation of 18F-FMAU and increased activity in lymph nodes, small intestine, stomach, and marrow because of varying degrees of increased cell proliferation. Increased activity was also seen in heart because of high level of thymidine kinase 2.

 


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  		FIGURE 2. 18F-FMAU retention curves for marrow, muscle, and blood of normal dog. Curves were obtained from dynamic PET with field of view over upper abdomen and lower chest, yielding a series of timed images for up to 60 min. Additional time point beyond 60 min was obtained from whole-body scan acquired about 65 min after injection. Estimate of time, 117 min after injection in this figure, was based on time when organ of interest was in field of view. Marrow activity was not corrected for partial volumes, and marrow-to-blood ratio was 12.3 in tissue samples removed at 160 min after injection.

 


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  		FIGURE 3. FMAU DNA incorporation (n = 3). Three normal dogs were used for this study. One dog was sacrificed at 160 min after injection ({blacktriangleup}), and the other 2 dogs were sacrificed at 60 min after injection (•). All tissue samples were analyzed by acid precipitation to determine DNA fraction. Sm = small.

 




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