Molecular Magnetic Resonance Imaging of Tumor Response to Therapy

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.

Rethinking cancer nanotheranostics

“…In preclinical studies, tumours are often implanted subcutaneously, and their dimensions can be easily measured by calipers. Tumours that are inoculated into internal organs have often been genetically engineered to express fluorescent, bioluminescent, MRI or PET reporters, so that their tumour load can be monitored non-invasively 93,94 . However, these techniques are obviously not viable in the clinic.…”

Using MRI cell tracking to monitor immune cell recruitment in response to a peptide‐based cancer vaccine

“…However, molecular imaging can also be a valuable research tool to explore and understand longitudinal molecular mechanisms initiated by novel cancer therapies both preclinically and clinically (15)(16)(17)(18)(19)(20)(21)(22). A variety of imaging modalities (i.e., MRI, PET, or fluorescence) have been used to investigate the effect of these therapies preclinically (15)(16)(17)(18)(19)(20)(21)(22). Fluorescence or bioluminescence optical imaging is common in the context of monitoring intensity changes and migration of therapeutics conjugated to fluorescent tags or specific cell types genetically modified for bioluminescence.…”

Enhancing Value of MRI: A Call for Action

“…Recent advances in molecular MRI expand the capability of MRI even further. Molecular probes activated by an enzyme and localized by nanoparticles, molecular imaging biomarkers for metabolites of activated T cells for immunotherapy, hyperpolarized gas‐enhanced MRI, and quantitative analysis of MR spectroscopy of glutathione, gamma‐aminobutyric acid (GABA), glutamate, with high accuracy and reproducibility are just a few examples. MRI continues to contribute to the scientific discovery and understanding of many diseases that were never thought possible.…”