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; Graves, Edward E.; Rutt, Brian; Rao, Jianghong; Wittrup, Karl Dane; ... Show more Show less
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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.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Chemical Engineering
Nature Publishing Group
Shuhendler, Adam J., Deju Ye, Kimberly D. Brewer, Magdalena Bazalova-Carter, Kyung-Hyun Lee, Paul Kempen, K. Dane Wittrup, Edward E. Graves, Brian Rutt, and Jianghong Rao. “Molecular Magnetic Resonance Imaging of Tumor Response to Therapy.” Scientific Reports 5 (October 6, 2015): 14759.
Final published version