Abstract
Several new tracers are being developed for use with PET to assess pathways that are altered in cancers, including energy use, cellular signaling, transport, and proliferation. Because increased proliferation is a hallmark of many cancers, several tracers have been tested to track the DNA synthesis pathway. Thymidine, which is incorporated into DNA but not RNA, has been used in laboratory studies to measure tumor growth. Because thymidine labeled with 11C undergoes rapid biologic degradation and has a short physical half-life, tracers labeled with 18F have been preferred in PET imaging. One such tracer is 18F-labeled 3′-deoxy-3′-fluorothymidine (18F-FLT). 18F-FLT is trapped after phosphorylation by thymidine kinase 1, whose expression is increased in replicating cells. Several studies on breast, lung, and brain tumors have demonstrated that retention of 18F-FLT correlated with tumor proliferation. Although 18F-FLT has been used to image and stage several tumor types, the standardized uptake value is generally lower than that obtained with 18F-FDG. 18F-FLT can be used to image many areas of the body, but background uptake is high in the liver, marrow, and renal system, limiting use in these organs. 18F-FLT PET imaging has primarily been studied in the assessment of treatment response. Rapid declines in 18F-FLT retention within days to weeks have been demonstrated in several tumor types treated with cytotoxic drugs, targeted agents, and radiotherapy. Further work is ongoing to validate this approach and determine its utility in the development of new drugs and in the clinical evaluation of standard treatment approaches.
Footnotes
Published online May. 14, 2013.
Learning Objectives: On successful completion of this activity, participants should be able to discuss (1) the radiopharmaceuticals used to evaluate cell proliferation; (2) the normal biodistribution of these radiopharmaceuticals; and (3) the role of these radiopharmaceuticals in the evaluation of malignancies.
Financial Disclosure: This work was partially supported by grant CA22453 from the National Cancer Institute and by U.S. Department of Defense Award W81XWH-10-2-0068. The authors of this article have indicated no other relevant relationships that could be perceived as a real or apparent conflict of interest.
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- © 2013 by the Society of Nuclear Medicine and Molecular Imaging, Inc.