Monitoring Antiproliferative Responses to Kinase Inhibitor Therapy in Mice with 3a€2-Deoxy-3a€2-18F-Fluorothymidine PET

摘要

id="p-1">The aim of this study was to evaluate, whether PET with 18F-FDG and 3a€2-deoxy-3a€2-18F-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.