PT  - JOURNAL ARTICLE
AU  - Gao, Liquan
AU  - Liu, Hao
AU  - Sun, Xianlei
AU  - Gao, Duo
AU  - Zhang, Chenran
AU  - Jia, Bing
AU  - Zhu, Zhaohui
AU  - Wang, Fan
AU  - Liu, Zhaofei
TI  - Molecular Imaging of Post-Src Inhibition Tumor Signatures for Guiding Dasatinib Combination Therapy
AID  - 10.2967/jnumed.115.158881
DP  - 2016 Feb 01
TA  - Journal of Nuclear Medicine
PG  - 321--326
VI  - 57
IP  - 2
4099  - http://jnm.snmjournals.org/content/57/2/321.short
4100  - http://jnm.snmjournals.org/content/57/2/321.full
SO  - J Nucl Med2016 Feb 01; 57
AB  - Noninvasive, real-time, quantitative measurement of key biomarkers associated with cancer therapeutic interventions could provide a better understanding of cancer biology. We investigated in this study whether incorporating multiple molecular imaging approaches could be used to guide dasatinib anti-Src therapy and aid in the rational design of a combination therapy regimen. Methods: Bioluminescence imaging, 18F-FDG PET, integrin αvβ3–targeted SPECT/CT, and vascular endothelial growth factor–targeted near-infrared fluorescence imaging were performed before and after dasatinib treatment in a tumor mouse model. Results: There was no significant difference in the bioluminescence imaging signal or 18F-FDG tumor uptake in dasatinib-treated tumors compared with the control tumors. However, the uptake of 99mT-3PRGD2 (integrin αvβ3–specific) and DyLight755-ranibizumab (vascular endothelial growth factor–specific) in the dasatinib-treated tumors was significantly lower than that in the control tumors. In vitro studies confirmed the antiangiogenic effects of dasatinib but indicated a lack of cytotoxicity. Dasatinib plus cytotoxic docetaxel elicited marked synergistic tumor growth inhibition in vivo. Conclusion: Visualization of post-Src inhibition tumor signatures through multiple imaging approaches facilitates sensitive and quantitative measurement of cancer biomarkers in vivo, thus aiding in the rational design of dasatinib combination therapy.