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

Journal of Nuclear Medicine

Michael E. Phelps¹  Johannes Czernin¹  Christian Waldherr¹  Ingo K. Mellinghoff¹  Arash Safaei¹  Benjamin S. Halpern¹  Nagichettiar Satyamurthy¹  Wolfgang A. Weber¹  David Stout¹  Jorge Barrio¹  Daniel H. Silverman¹  Charles L. Sawyers¹  Nora Rozengurt¹  Chris Tran¹ 

关键词: thymidine kinase;    ErbB;    small molecule kinase inhibitor;    ¹⁸F-FDG PET;    ¹⁸F-FLT PET;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

Unknown