Molecular Magnetic Resonance Imaging of Tumor Response to Therapy

• Main Authors: Shuhendler, Adam J. (Author), Ye, Deju (Author), Brewer, Kimberly D. (Author), Bazalova-Carter, Magdalena (Author), Lee, Kyung-Hyun (Author), Kempen, Paul (Author), Graves, Edward E. (Author), Rutt, Brian (Author), Rao, Jianghong (Author), Wittrup, Karl Dane (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Chemical Engineering (Contributor), Koch Institute for Integrative Cancer Research at MIT (Contributor)
• Format: Article
• Language: English
• Published: Nature Publishing Group, 2015-12-29T00:10:35Z.
• Subjects: Article
• Online Access: Get fulltext

 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.