Molecular Imaging of Post-Src Inhibition Tumor Signatures for Guiding Dasatinib Combination Therapy
Liquan Gao1, Hao Liu1, Xianlei Sun1
1Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Unlabelled:
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, (18)F-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 (18)F-FDG tumor uptake in dasatinib-treated tumors compared with the control tumors. However, the uptake of (99m)T-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.
Insights
Multiple molecular imaging techniques revealed dasatinib
Area of Science:
- Oncology
- Molecular Imaging
- Pharmacodynamics
Background:
- Noninvasive, real-time biomarker measurement is crucial for understanding cancer biology and guiding therapeutic interventions.
- Dasatinib is a targeted therapy for cancer, but its precise effects and optimal combination strategies require further elucidation.
Purpose of the Study:
- To investigate the utility of multiple molecular imaging approaches in guiding dasatinib anti-Src therapy.
- To aid in the rational design of combination therapy regimens involving dasatinib.
Main Methods:
- Utilized bioluminescence imaging, (18)F-FDG PET, integrin αvβ3-targeted SPECT/CT, and VEGF-targeted near-infrared fluorescence imaging in a tumor mouse model.
- Performed imaging before and after dasatinib treatment to assess therapeutic response.
Main Results:
- Dasatinib treatment did not significantly alter bioluminescence or (18)F-FDG uptake.
- Targeted imaging showed significantly reduced uptake of integrin αvβ3 and VEGF markers in dasatinib-treated tumors, indicating antiangiogenic effects.
- In vitro studies confirmed dasatinib's antiangiogenic activity without significant cytotoxicity.
- Combination of dasatinib with docetaxel resulted in synergistic tumor growth inhibition.
Conclusions:
- Multiple imaging modalities can visualize tumor biomarker changes after dasatinib treatment, enabling quantitative assessment.
- This approach aids in understanding dasatinib's effects and designing effective combination therapies for cancer.
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