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Open Access Publications from the University of California

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.

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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.

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