Format

Send to

Choose Destination
J Nucl Med. 2016 Feb;57(2):321-6. doi: 10.2967/jnumed.115.158881. Epub 2015 Sep 17.

Molecular Imaging of Post-Src Inhibition Tumor Signatures for Guiding Dasatinib Combination Therapy.

Author information

1
Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
2
Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing, China; and.
3
Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
4
Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China liuzf@bjmu.edu.cn.

Abstract

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.

KEYWORDS:

Src family of kinases; angiogenesis; dasatinib; image-guided therapy; tumor response

PMID:
26383149
DOI:
10.2967/jnumed.115.158881
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center