MRI Technology Enables Noninvasive Monitoring of Emergent Cell Therapies

Cellular therapeutics, the application of using intact cells to treat and cure disease, is an important potential new therapeutic application, but it is hampered by the inability of clinicians and scientists to effectively monitor the destination, movements, and perseverance of these cells in patients without having to use invasive procedures, such as tissue sampling.

In a study published September 19, 2014, in the online journal Magnetic Resonance in Medicine, researchers from the University of California (UC), San Diego School of Medicine (USA), University of Pittsburgh, and elsewhere describe the first human tests of using a perfluorocarbon (PFC) tracer in combination with noninvasive magnetic resonance imaging (MRI) scanning to track therapeutic immune cells injected into colorectal cancer patients.

“Initially, we see this technique used for clinical trials that involve tests of new cell therapies,” said first author Eric T. Ahrens, PhD, professor in the department of radiology at UC San Diego. “Clinical development of cell therapies can be accelerated by providing feedback regarding cell motility, optimal delivery routes, individual therapeutic doses, and engraftment success.”

Currently, there is no accepted way to image cells in the human body that includes a broad range of cell types and diseases. Earlier strategies have employed metal ion-based vascular MRI contrast agents and radioisotopes. The former have been shown to be difficult to differentiate in vivo; the latter raise apprehensions about radiation toxicity and do not provide the anatomic facets available with MRI scans. “This is the first human PFC cell tracking agent, which is a new way to do MRI cell tracking,” said Dr. Ahrens. “It’s the first example of a clinical MRI agent designed specifically for cell tracking.”

Researchers utilized a PFC tracer agent and an MRI technique that directly identifies fluorine atoms in labeled cells. Fluorine atoms naturally occur in extremely low concentrations in the body, making it easier to see cells labeled with fluorine using MRI scanning. In this instance, the engineered and labeled dendritic cells—powerful stimulators of the immune system—were first prepared from white blood cells extracted from the patient. The cells were then injected into patients with stage 4 metastatic colorectal cancer to trigger an anticancer T-cell immune response.

The published study did not evaluate the effectiveness of the cell therapy, but instead the ability of researchers to detect the labeled cells and monitor what occurred to them. Ahrens said the technique worked as expected, with the unanticipated finding that only half of the delivered cell vaccine remained at the inoculation site after 24 hours.

“The imaging agent technology has been to shown to be able to tag any cell type that is of interest,” Dr. Ahrens concluded. “It is a platform imaging technology for a wide range of diseases and applications, which might also speed development of relevant therapies. Noninvasive cell tracking may help lower regulatory barriers. For example, new stem cell therapies can be slow to obtain regulatory approvals in part because it is difficult, if not impossible, with current approaches to verify survival and location of transplanted cells. And cell therapy trials generally have a high cost per patient. Tools that allow the investigator to gain a ‘richer’ data set from individual patients mean it may be possible to reduce patient numbers enrolled in a trial, thus reducing total trial cost.”

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University of California, San Diego School of Medicine