Novel Imaging Technique Using Noninvasive MRI, PFC Tracer Described

Researchers described the first human tests of the use of a perfluorocarbon (PFC) tracer in combination with MRI to track therapeutic immune cells injected into patients with colorectal cancer in a paper published in the online journal Magnetic Resonance in Medicine.

Researchers at the University of California, San Diego School of Medicine; University of Pittsburgh; and elsewhere are investigating cellular therapeutics. The promising new approach is hindered by the inability of physicians and scientists to effectively track the movements, destination, and persistence of these cells in patients without resorting to invasive procedures such as tissue sampling.

Currently, there is no accepted way to image cells in the human body that covers a broad range of cell types and diseases. Earlier techniques have used metal ion-based vascular MRI contrast agents and radioisotopes. The former have proven difficult to differentiate in vivo; the latter raise concerns about radiation toxicity and do not provide the anatomical detail available with MRIs.

"This is the first human PFC cell-tracking agent, which is a new way to do MRI cell tracking," says first author Eric T. Ahrens, PhD, a professor in the department of radiology at UC San Diego. "It's the first example of a clinical MRI agent designed specifically for cell tracking."

Researchers used a PFC tracer agent and an MRI technique that directly detects fluorine atoms in labeled cells. Fluorine atoms naturally occur in extremely low concentrations in the body, making it easier to observe cells labeled with fluorine using MRI. In this case, the modified and labeled dendritic cells—potent 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 stimulate an anticancer T-cell immune response.

The published study did not assess the efficacy of the cell therapy, but rather the ability of researchers to detect the labeled cells and monitor what happened to them. Ahrens says the technique worked as expected, with the surprising finding that only one-half of the delivered cell vaccine remained at the inoculation site after 24 hours.

"Noninvasive cell tracking may help lower regulatory barriers," Ahrens explains. "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."

— SOURCE: University of California, San Diego