PT  - JOURNAL ARTICLE
AU  - Waldherr, Christian
AU  - Mellinghoff, Ingo K.
AU  - Tran, Chris
AU  - Halpern, Benjamin S.
AU  - Rozengurt, Nora
AU  - Safaei, Arash
AU  - Weber, Wolfgang A.
AU  - Stout, David
AU  - Satyamurthy, Nagichettiar
AU  - Barrio, Jorge
AU  - Phelps, Michael E.
AU  - Silverman, Daniel H.
AU  - Sawyers, Charles L.
AU  - Czernin, Johannes
TI  - Monitoring Antiproliferative Responses to Kinase Inhibitor Therapy in Mice with 3′-Deoxy-3′-<sup>18</sup>F-Fluorothymidine PET
DP  - 2005 Jan 01
TA  - Journal of Nuclear Medicine
PG  - 114--120
VI  - 46
IP  - 1
4099  - http://jnm.snmjournals.org/content/46/1/114.short
4100  - http://jnm.snmjournals.org/content/46/1/114.full
SO  - J Nucl Med2005 Jan 01; 46
AB  - 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.