Development of (18)F-labeled PET probes for imaging cell proliferation

In recent years, two different methods have been developed to image cell proliferation with the functional imaging technique, Positron emission Tomography (PET), proliferation rate and proliferative status. Proliferation rate is a measure of the tumor doubling time and uses radiolabeled analogs of the DNA precursor thymidine. This approach measures the activity of the enzyme thymidine kinase 1 (TK1) and provides a pulse label of the S phase fraction of a tumor. Proliferative status provides a measure of the ratio of proliferating (P) and quiescent (Q) cells in a tumor. This imaging approach for measuring proliferative status involves measuring the sigma-2 (σ(2)) receptor status of a tumor, the only protein which has been validated for making this measurement in vivo with PET. This article provides an overview of the biological information obtained from these different imaging strategies, and the development of radiotracers for imaging proliferation rate and proliferative status.