Tumor hypoxia appears to be strongly associated with tumor propagation, malignant progression, and resistance to therapy and it has thus become a central issue in tumor physiology and cancer treatment. The ability to quantitatively measure tumor oxygenation could be of great value to cancer diagnosis and prognosis. Previous work from our lab has identified hexamethyldisiloxane (HMDSO) as a promising proton MRI pO2 reporter molecule for NMR spectroscopy and imaging, since its spin-lattice relaxation rate is sensitive to oxygen tension. HMDSO is non-toxic, readily available, hydrophobic, and has a long retention time in tumor. For further application of this 1H MRI pO2 reporter, we propose to develop biocompatible HMDSO nanoemulsions for systemic delivery of this pO2 reporter molecule and demonstrate in vivo application. While 19F MR oximetry using perflourinated compounds such as hexafluorobenzene is routinely used for basic research, a 1H MRI analogue would have greater and more rapid potential for clinical application. The overall objective of the proposed research is to develop HMDSO based nanoemulsions as a proton MRI pO2 reporter nanoprobes and to use them to explore the tumor microenviromental response to combination chemotherapy.
|Effective start/end date||3/6/12 → 8/31/13|
- HHS-NIH: National Cancer Institute (NCI): $70,209.00