Low-molecular weight lanthanide contrast agents: Evaluation of susceptibility and dipolar effects in red blood cell suspensions

Red blood cell (RBC) suspensions, containing low-molecular weight (LMW) dysprosium (Dy) and gadolinium (Gd) chelates, were selected as a two-compartment system for the evaluation of the magnetic dipolar and susceptibility contributions to the transverse (T-2) relaxation of solvent mater protons, The influence of RBC geometry and degree of metal chelate compartmentalization on T-2 was investigated by variation of the osmolality and hematocrit (HC), respectively, The T-2-relaxation ability of Dy-chelates was markedly improved in RBC suspensions, in comparison to aqueous solutions, due to the presence of susceptibility effects that more than compensated for the low dipolar relaxation efficacy, Despite a smaller susceptibility effect, the Gd-chelates were still the most efficacious in shortening T-2 due to their comparatively larger dipolar relaxation contribution, The results obtained with the Dy-chelates allowed the evaluation of the relative contributions of susceptibility and dipolar mediated relaxation for the Gd-chelates. The RBC geometry and degree of compartmentalization influenced strongly the T-2 relaxation efficacy of Dy-chelates, as opposed to the Gd-chelates. Hemolysis eliminated the susceptibility effect, essentially removing the T-2 relaxation ability of Dy-chelates. The T-2 relaxation efficacy of Gd-chelates was improved by hemolysis due to enhancement of the dipolar relaxation. As a conclusion, RBC suspensions have clearly been shown to be a suitable ex vivo model with which to distinguish the different contrast mechanisms of LMW Dy- and Gd-based MRI contrast agents. (C) 1997 Elsevier Science Inc.