Manganese-based macrocyclic chelates as novel MRI contrast agents: In vivo imaging in a porcine model

TL;DR

This study investigates novel manganese-based macrocyclic chelates as MRI contrast agents in pigs, demonstrating their comparable efficacy and potential safety advantages over traditional gadolinium-based agents.

Contribution

The paper introduces new Mn-based macrocyclic chelates and evaluates their in vivo imaging performance, showing they are effective and may offer safety benefits over Gd-based agents.

Findings

GEH200486 showed the largest T1 relaxation rate increase

All agents exhibited similar plasma kinetics with rapid distribution and slower elimination

Manganese chelates demonstrated effective contrast enhancement comparable to Gd agents

Abstract

Objectives: Mn-based MRI contrast agents (MBCAs) have recently been proposed as alternatives to the currently used class of Gd-chelates. Unlike Gd, Mn is an endogenous paramagnetic metal with known biochemical pathways in the human body for excretion and metal regulation, which may alleviate the raised concerns about the safety of existing GBCAs. The aim of this study was to investigate the distribution, kinetics and image enhancement properties of a class of novel Mn-based macrocyclic chelates in a porcine model. Methods: Macrocyclic MBCAs, AH114608, GEH300017 and GEH200486, were tested and compared to gadoterate meglumine. Twelve female adult pigs were divided into four groups (n=3 for each CA). At 3 T MRI, T1 relaxometry analysis were measured longitudinally in multiple organs at five timepoints 30 minutes apart. CA kinetics was estimated from analysis of plasma CA concentrations by ICP-OES. Results: All four CAs exhibited T1-enhancing properties in the blood pool with GEH200486 having the largest increase in T1 relaxation rate (R1), GEH300017 and gadoterate meglumine having similar R1 increase and AH114608 a lower peak R1 change. A persistent increase in liver, kidney and myocardium R1 was observed with AH114608. To a lesser extent, a persistent increase of liver enhancement was also observed in T1-weighted images for GEH300017 and GEH200486 compared to gadoterate meglumine. All four CAs had similar bi-exponential plasma kinetics characterized by a rapid distribution phase and a slower elimination phase. Discussion: We have identified MBCA candidates with predominantly renal clearance and comparable efficacy in terms of vascular T1 relaxation, and comparable to the reference GBCA. The T1-enhancing properties of these novel Mn macrocyclic CAs can be used with routine clinical protocols and could be potentially utilised as an alternative to GBCAs for contrast-enhanced MRI procedures.