MRI-based cell tracking of OATP-expressing cell transplants by pre-labeling with Gd-EOB-DTPA.

ABSTRACT

Purpose: A critical step in cell-based therapies is determining the exact position of transplanted cells immediately post-transplant. Here, we devised a method to detect cell transplants immediately post-transplant, using a clinical gadolinium-based contrast agent. These cells were detected as hyperintense signals using a clinically familiar T1-weighted MRI protocol. Procedures HEK293 cells were stably transduced to express human OATP1B3, a hepatic organic anion transporting polypeptide that transports Gd-EOB-DTPA into cells that express the transporters, the intracellular accumulation of which cells causes signal enhancement on T1-weighted MRI. Cells were pre-labeled prior to injection in media containing Gd-EOB-DTPA for MRI evaluation and indocyanine green for cryofluorescence tomography validation. Labeled cells were injected into chicken hearts, in vitro, after which MRI and cryofluorescence tomography were performed in sequence. Results: OATP1B3-expressing cells had substantially reduced T1 following labeling with Gd-EOB-DTPA in culture. Following their implantation into chicken heart, these cells were robustly identified in T1-weighted MRI, with image-derived injection volumes of cells commensurate with intended injection volumes. Cryofluorescence tomography showed that the areas of signal enhancement in MRI overlapped with areas of indocyanine green signal, indicating that MRI signal enhancement was due to the transplanted cells. Conclusions: OATP1B3-expressing cells can be pre-labeled with Gd-EOB-DTPA prior to injection into tissue, affording the use of clinically familiar T1-weighted MRI to robustly detect cell transplants immediately after transplant. This procedure is easily generalizable and has potential advantages over the use of iron oxide based cell labeling agents and imaging procedures.