Nuclear Imaging of Cellular Proliferation

Yeo, Jeong Seok

Abstract

Tumor cell proliferation is considered to be a useful prognostic indicator of tumor aggressiveness and tumor response to therapy, but in vitro measurement of individual proliferation is complex and tedious work. PET imaging provides a noninvasive approach to measure tumor growth rate in situ. Early approaches have used 18F-FDG or methionine to monitor proliferation status. These 2 tracers detect changes in glucose and amino acid metabolism, respectively, and therefore provide only an indirect measure of proliferation status. More recent studies have focused on DNA synthesis itself as a marker of cell proliferation. Cell lines and tissues with a high proliferation rate require high rates of DNA synthesis. [11C]Thymidine was the first radiotracer for noninvasive imaging of tumor proliferation. The short half-life of 11C and rapid metabolism of [11C]thymidine in vivo make the radiotracer less suitable for routine use. Halogenated thymidine analogs such as 5-iodo-2-deoxyuridine (IUdR) can be successfully used as cell proliferation markers for in vitro studies because these compounds are rapidly incorporated into newly synthesized DNA. IUdR has been evaluated as a potential in vivo tracer in nuclear medicine, but the image quality and the calculation of proliferation rates are impaired by its rapid in vivo degradation. Hence, the thymidine analog 3'-deoxy-3'-18F-fluorothymidine (FLT) was recently introduced as a stable proliferation marker with a suitable nuclide half-life and stable in vivo. [18F]FLT is phosphorylated to 3-fluorothymidine monophosphate by thymidine kinase 1 and reflects thymidine kinase 1 activity in proliferating cell. [18F]FLT PET is feasible in clincal use and well correlates with cellular proliferation. Choline is a precursor for the biosynthesis of phospholipids (in particular, phosphatidylcholine), which is the essential component of all eukaryotic cell membranes and [11C]choline, which is a new marker for cellular proliferation.