Figure 4. [18F]-FLUOROTHYMIDINE

The synthesis of 11C and 18F-thymidine and the development of PET instrumentation led to the ability to image thymidine uptake and measure cell growth noninvasively. 18F-FLT is  a valuable marker of tumor response to antiproliferative treatments including RT.

DNA synthesis is required for cell growth and proliferation, nucleotides of the four bases (cytosine, guanine, adenine, and thymidine) are required for this task, 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 provides a measure of DNA synthesis independent of RNA synthesis, therefore, thymidine incorporation into DNA is considered a gold standard measure of proliferation.

PET- CT with [11C]-thymidine represents the standard for imaging proliferation, because it is identical to native thymidine, eliminating potential differences in uptake caused by differences in metabolism between thymidine and its analogues.

Thymidine outside the cell can be incorporated into DNA by the exogenous pathway:
 Flux through this pathway is ultimately controlled by the rate of DNA synthesis and is controlled by thymidine kinase.
T-MP: thymidine monophosphate
T-DP: thymidine diphosphate
T-TP: thymidine triphosphate


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