Monitoring antiproliferative responses to kinase inhibitor therapy in mice with 3′-deoxy-3′-18F-fluorothymidine PET

Christian Waldherr, Ingo K. Mellinghoff, Chris Tran, Benjamin S. Halpern, Nora Rozengurt, Arash Safaei, Wolfgang A. Weber, David Stout, Nagichettiar Satyamurthy, Jorge Barrio, Michael E. Phelps, Daniel H. Silverman, Charles L. Sawyers, Johannes Czernin

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

104 Zitate (Scopus)

Abstract

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.

OriginalspracheEnglisch
Seiten (von - bis)114-120
Seitenumfang7
FachzeitschriftJournal of Nuclear Medicine
Jahrgang46
Ausgabenummer1
PublikationsstatusVeröffentlicht - 2005
Extern publiziertJa

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