Molecular Magnetic Resonance Imaging of Tumor Response to Therapy

Sci Rep. 2015 Oct 6;5:14759. doi: 10.1038/srep14759.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Metronomic
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Caspase 3 / metabolism
  • Contrast Media* / chemistry
  • Cysteine / administration & dosage
  • Cysteine / analogs & derivatives
  • Cysteine / chemistry
  • Doxorubicin / administration & dosage
  • Female
  • HeLa Cells
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Mice, Nude
  • Neoplasms / drug therapy*
  • Neoplasms / pathology*
  • Neoplasms / radiotherapy
  • Quinolines / administration & dosage
  • Quinolines / chemistry
  • Treatment Outcome
  • Xenograft Model Antitumor Assays / methods

Substances

  • Antibiotics, Antineoplastic
  • C-SNAM compound
  • Contrast Media
  • Quinolines
  • Doxorubicin
  • Caspase 3
  • Cysteine