9 - Tumor Proliferation: 2-[11C]-Thymidine Positron Emission Tomography

Add time:09/03/2019    Source:sciencedirect.com

Publisher Summary[11C]-labeled-thymidine is the first radiotracer used for noninvasive imaging of tumor proliferation and one of the most appropriate pharmacodynamic tools to assess treatment response and assist early validation of novel anticancer agents, because its uptake is directly related to DNA synthesis and correlates with proliferation in human tumors. As a vital component for DNA synthesis, thymidine is essential for cell proliferation and is therefore also a key molecule for measuring tumor proliferation and an important target for cancer therapy. This methodology has been applied to the development of positron-emitting tracers that can provide a measure of cell proliferation in vivo using PET. While the identification of new therapeutic targets is important, the development of more accurate and relevant methods of measuring response to treatment is also vital, especially for the early assessment of new agents. Cancer treatment-induced changes in DNA cell proliferation are more pronounced than changes in glucose metabolism, further supporting the need for a direct marker to image and measure cell proliferation. In contrast, radiolabeled thymidine is incorporated into DNA, and its uptake is a direct measure of cell proliferation rate. Uptake of 2-[11C]-thymidine is related to DNA synthesis and, in comparison with 18F-FDG, has been shown to be a more sensitive discriminator of early clinical response in small cell lung cancer and sarcoma. But the short half-life of 11C and its rapid metabolism in vivo have inhibited its widespread clinical use.

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