Kinetic Modeling of 39-Deoxy-39-18F- Fluorothymidine for Quantitative Cell Proliferation Imaging in Subcutaneous Tumor Models in Mice

39-Deoxy-39-18F-fluorothymidine (18F-FLT) is a thymidine analog that was developed for measuring tumor proliferation with PET. The aim of this study was to establish a kinetic modeling analysis method for quantitative 18F-FLT PET studies in subcutaneous tumor models in mice. Methods: To explore the validity of an image-derived left ventricular input function, we measured equi-librium constants for plasma and whole blood and metabolite fractions in blood after 18F-FLT injection. In parallel, dynamic 18F-FLT PET scans were acquired in 24 mice with a small-animal dedicated PET scanner to compare arterial blood activities ob-tained by PET and blood sampling. We then investigated kinetic models for 18F-FLT in human epithelial carcinoma (A431) and Lewis lung carcinoma tumor models in mice. Three-compart-ment models with reversible phosphorylation (k4 6 0, 3C5P) and irreversible phosphorylation (k45 0, 3C4P) and a 2-compart