Transporter-Mediated Hepatic Uptake of EOB-DTPA and BOPTA Is Largely Independent of Chelated Metal.

PURPOSE: Metal chelates play a crucial role in diagnostic imaging and radiotherapy. While gadolinium-based chelates are widely used in MRI, radiometal chelates are increasingly used in nuclear medicine and theranostics. Despite their clinical importance, the extent to which the identity of the coordinated metal influences in vivo chelate pharmacology remains unclear. The goal of this work was to determine whether metal substitution alters transporter-mediated cellular uptake and pharmacological behavior of hepatospecific chelates.

PROCEDURES: Apo-forms of the clinical hepatospecific MRI contrast agents EOB-DTPA and BOPTA were generated and re-chelated with eight different metals (Sc, Y, Pr, Eu, Gd, Tb, Dy, Ho). In vitro transport of these chelates was assessed in cells expressing rodent and human hepatic transporters. In vivo hepatic uptake was evaluated in mice expressing either wild-type or human hepatic transporters. Tissue distribution and clearance were quantified analytically.

RESULTS

In vitro uptake of EOB-DTPA and BOPTA chelates by cells expressing rodent and human transporters showed no statistically significant differences across metals. In vivo studies in mice similarly showed no statistically significant differences in hepatic uptake across metals, with the exception of reduced uptake observed for Sc-EOB-DTPA in wild-type animals. No evidence of free metal accumulation in soft tissue was detected. Chelate clearance via renal and hepatobiliary pathways was similar across metals.

CONCLUSIONS

Within the class of trivalent metals examined and for EOB-DTPA and BOPTA chelates, transporter-mediated uptake, biodistribution, and clearance were largely independent of metal identity under the conditions tested. These findings support the use of common chelate scaffolds across multiple metals, while highlighting the importance of ligand structure and transporter interactions in governing pharmacology.