Scientists say they have devised a way to track the movements, destination, and persistence of a broad range of cellular therapies, without resorting to invasive procedures.
In Magnetic Resonance in Medicine, the researchers described the first human tests using a perfluorocarbon (PFC) tracer in combination with non-invasive magnetic resonance imaging (MRI) to track therapeutic immune cells injected into patients with colorectal cancer.
“Initially, we see this technique used for clinical trials that involve tests of new cell therapies,” said study author Eric T. Ahrens, PhD, of the University of California, 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 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,” Dr Ahrens said. “It’s the first example of a clinical MRI agent designed specifically for cell tracking.”
He and his colleagues 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 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 researchers did not assess the efficacy of the cell therapy, only their ability to detect the labeled cells and monitor what happened to them. Dr Ahrens said the technique worked as expected, with the surprising finding that only half of the delivered cell vaccine remained at the inoculation site after 24 hours.
“The imaging agent technology has been shown to be able to tag any cell type that is of interest,” Dr Ahrens said. “It is a platform imaging technology for a wide range of diseases and applications.”
“Non-invasive cell tracking may help lower regulatory barriers,” he added. “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.”
