TY - JOUR T1 - PET Imaging of Proliferation with Pyrimidines JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 903 LP - 912 DO - 10.2967/jnumed.112.112201 VL - 54 IS - 6 AU - Omid S. Tehrani AU - Anthony F. Shields Y1 - 2013/06/01 UR - http://jnm.snmjournals.org/content/54/6/903.abstract N2 - 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. ER -