Research Grants Program Office (RGPO)
Molecular Magnetic Resonance Imaging of Tumor Response to Therapy.
- Author(s): Shuhendler, Adam J
- Ye, Deju
- Brewer, Kimberly D
- Bazalova-Carter, Magdalena
- Lee, Kyung-Hyun
- Kempen, Paul
- Dane Wittrup, K
- Graves, Edward E
- Rutt, Brian
- Rao, Jianghong
- et al.
Published Web Locationhttps://doi.org/10.1038/srep14759
Personalized cancer medicine requires measurement of therapeutic efficacy as early as possible, which is optimally achieved by three-dimensional imaging given the heterogeneity of cancer. Magnetic resonance imaging (MRI) can obtain images of both anatomy and cellular responses, if acquired with a molecular imaging contrast agent. The poor sensitivity of MRI has limited the development of activatable molecular MR contrast agents. To overcome this limitation of molecular MRI, a novel implementation of our caspase-3-sensitive nanoaggregation MRI (C-SNAM) contrast agent is reported. C-SNAM is triggered to self-assemble into nanoparticles in apoptotic tumor cells, and effectively amplifies molecular level changes through nanoaggregation, enhancing tissue retention and spin-lattice relaxivity. At one-tenth the current clinical dose of contrast agent, and following a single imaging session, C-SNAM MRI accurately measured the response of tumors to either metronomic chemotherapy or radiation therapy, where the degree of signal enhancement is prognostic of long-term therapeutic efficacy. Importantly, C-SNAM is inert to immune activation, permitting radiation therapy monitoring.