NIH develops method to label, track cells with MRI
Researchers with the National Institutes of Health (NIH) have developed a method to label transplanted cells so they can be tracked by MRI, potentially offering a way to measure how many transplanted immune or stem cells reach their target during cell therapy.
Joseph A. Frank, MD, chief of the NIH Clinical Center Radiology and Imaging Sciences Laboratory of Diagnostic Radiology Research, and colleagues formed a complex that, when incubated in transplant cells, labeled nearly 100 percent of those cells for MR imaging in animal models.
"Less than 3 percent of intravenous transplanted cells get to their target. This brings up questions of cell dose, multiple doses and dose timing and how to make cell therapy approaches more effective," Frank said in a statement. Cell death and distribution to other areas prevent most treatment cells from reaching the intended site.
In current clinical practice, cell tracking is done with radioisotopes or implantation of an easily located reporter gene, but short half-life of isotopes, modification to the cell genome and the possibility of toxicity limit these methods.
The complex created by the researchers is a combination of three FDA-approved drugs. Ferumoxytol is a drug with iron oxide and magnetic properties that allow for MRI tracking. The other two drugs, negatively-charged heparin and positively-charge protamine, allow for successful and smooth incorporation into the transplant cell. Since these three drugs are used clinically, extensive safety testing should not be necessary and the investigative new drug application evaluation should be shortened, according to NIH.
The tracking method, pending regulatory agency review, will be first tested in humans in an ongoing trial at the City of Hope Medical Center in Duarte, Calif. Supported by the California Institute of Regenerative Medicine, the study is testing the transplant of genetically engineered neural stem cells on patients with a specific type of brain tumor.
Joseph A. Frank, MD, chief of the NIH Clinical Center Radiology and Imaging Sciences Laboratory of Diagnostic Radiology Research, and colleagues formed a complex that, when incubated in transplant cells, labeled nearly 100 percent of those cells for MR imaging in animal models.
"Less than 3 percent of intravenous transplanted cells get to their target. This brings up questions of cell dose, multiple doses and dose timing and how to make cell therapy approaches more effective," Frank said in a statement. Cell death and distribution to other areas prevent most treatment cells from reaching the intended site.
In current clinical practice, cell tracking is done with radioisotopes or implantation of an easily located reporter gene, but short half-life of isotopes, modification to the cell genome and the possibility of toxicity limit these methods.
The complex created by the researchers is a combination of three FDA-approved drugs. Ferumoxytol is a drug with iron oxide and magnetic properties that allow for MRI tracking. The other two drugs, negatively-charged heparin and positively-charge protamine, allow for successful and smooth incorporation into the transplant cell. Since these three drugs are used clinically, extensive safety testing should not be necessary and the investigative new drug application evaluation should be shortened, according to NIH.
The tracking method, pending regulatory agency review, will be first tested in humans in an ongoing trial at the City of Hope Medical Center in Duarte, Calif. Supported by the California Institute of Regenerative Medicine, the study is testing the transplant of genetically engineered neural stem cells on patients with a specific type of brain tumor.