MRI of OATP-expressing transplanted cells using clinical doses of gadolinium contrast agent

Abstract

Hepatic organic anion transporting polypeptides (OATPs) transport off-the-shelf, FDA-approved, hepatospecific Gd-based MRI contrast agents into cells that express the transporters enhancing signal on clinical T1-weighted MRI. Studies have used MRI to identify OATP-overexpressing tumors and metastases in mice following the delivery of Gd-EOB-DTPA at 27-67-fold higher than clinical doses. With safety and regulatory concern over Gd-based contrast agents, translation of this imaging paradigm to humans for regenerative medicine cell therapy will require substantially lower doses of agent. Here we complemented static T1-weighted MRI and/or T1-mapping with dynamic contrast enhanced (DCE)-MRI and show that even low intracellular accumulation of contrast agent results in a sustained signal enhancement in OATP-overexpressing tumors while control, non-expressing tumors have rapid wash-in and wash-out dynamics which could be distinguished by performing area-under-the-curve (AUC) analyses.