PET imaging of cellular proliferation

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Biologic and quantitative considerations

DNA synthesis is required for cell growth and proliferation [1]. Nucleotides of the four bases (cytosine, guanine, adenine, and thymidine) are required for DNA synthesis, and measurements of the rate of their incorporation into DNA yield the DNA synthetic rate. Of the four nucleosides, thymidine is the only one incorporated exclusively into DNA, and not RNA, and provides a measure of DNA synthesis independent of RNA synthesis [2]. Thymidine exogenous to the cell can be incorporated into DNA by

Clinical applications of cellular proliferation imaging

At this time, proliferation imaging is not used in routine clinical practice. A variety of pilot clinical studies have been conducted for [11C]-thymidine and more recently for the analogues, especially FLT. Studies in patients are reviewed, with an emphasis on feasibility, image interpretation and quantitative analysis, and likely future clinical applications.

Summary

PET cellular proliferation imaging has its roots in a long history of in vitro cellular proliferation studies to characterize cancer and in the understanding of the biology of thymidine incorporation into DNA gained from these studies. PET imaging represents the logical translation of the in vitro work to measure in vivo tumor proliferation. Preclinical studies of [11C]-thymidine and other PET-labeled thymidine analogues set the stage for early clinical studies that provided very promising

Acknowledgments

The authors acknowledge John R. Grierson, Janet F. Eary, and Alexander M. Spence for illustrations, patient examples, and helpful discussions; and Mark Muzi and Jeanne M. Link for collaborations and helpful discussions regarding data analysis and metabolite analysis methods.

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    Supported by NIH Grants P01 CA42045, R01 CA72064, RO1 CA39566, K24 CA82645, and RO1 CA83131.

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