TY - JOUR T1 - Monitoring Antiproliferative Responses to Kinase Inhibitor Therapy in Mice with 3′-Deoxy-3′-<sup>18</sup>F-Fluorothymidine PET JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 114 LP - 120 VL - 46 IS - 1 AU - Christian Waldherr AU - Ingo K. Mellinghoff AU - Chris Tran AU - Benjamin S. Halpern AU - Nora Rozengurt AU - Arash Safaei AU - Wolfgang A. Weber AU - David Stout AU - Nagichettiar Satyamurthy AU - Jorge Barrio AU - Michael E. Phelps AU - Daniel H. Silverman AU - Charles L. Sawyers AU - Johannes Czernin Y1 - 2005/01/01 UR - http://jnm.snmjournals.org/content/46/1/114.abstract N2 - The aim of this study was to evaluate, whether PET with 18F-FDG and 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) may be used to monitor noninvasively the antiproliferative effects of tyrosine kinase inhibitors. Methods: Using a high-resolution small animal scanner, we measured the effect of the ErbB-selective kinase inhibitor PKI-166 on the 18F-FDG and 18F-FLT uptake of ErbB1-overexpressing A431 xenograft tumors. Results: Treatment with PKI-166 markedly lowered tumor 18F-FLT uptake within 48 h of drug exposure; within 1 wk 18F-FLT uptake decreased by 79%. 18F-FLT uptake by the xenografts significantly correlated with the tumor proliferation index as determined by proliferating cell nuclear antigen staining (r = 0.71). Changes in 18F-FLT uptake did not reflect inhibition of ErbB kinase activity itself but, rathe, the effects of kinase inhibition on tumor cell proliferation. Tumor 18F-FDG uptake generally paralleled the changes seen for 18F-FLT. However, the baseline signal was significantly lower than that for 18F-FLT. Conclusion: These results indicate that 18F-FLT PET provides noninvasive, quantitative, and repeatable measurements of tumor cell proliferation during treatment with ErbB kinase inhibitors and provide a rationale for the use this technology in clinical trials of kinase inhibitors. ER -