NMRD assessment of Gd-DTPA-bis(methoxyethylamide), (Gd-DTPA-BMEA), a nonionic MRI agent

Abstract

RATIONALE AND OBJECTIVES. Gd-DTPA-BMEA, a nonionic bis(methoxyethylamide) derivative of Gd-DTPA, is the active ingredient of OptiMARK,(R) now awaiting FDA approval. In this study, we compare the relaxivities of Gd-DTPA-BMEA (OptiMARK(R)) with those of the commercially available DTPA-based agents Gd-DTPA2- (Magnevist(R)) and Gd-DTPA-BMA (Omniscan(R)) at different field strengths (1/T1 nuclear magnetic relaxation dispersion (NMRD) profiles). In addition, we study how changes in structural attributes of small paramagnetic chelate complexes of Gd3+ ions influence 1/T1 NMRD profiles. METHODS. 1/T1 NMRD profiles of Gd-DTPA-BMEA (OptiMARK(R)) were measured at 5°and 35°C and a set of values for the parameters that describe relaxation by Gd3+-proton magnetic dipolar interactions was obtained. The rotational (τ(R)) and the diffusional (τ(D)) correlation times for Gd-DTPA-BMA were adjusted for the 15% greater molecular weight of Gd-DTPA-BMEA. τ(M) (the resident lifetime of Gd3+-bound water) was obtained from available 17O NMR relaxation data. For τ(SO) and τ(V) (the low-field relaxation time of the Gd3+ moment and its correlation time), the Gd-DTPA-BMA values were taken as initial values and τ(SO) refined as needed. RESULTS. Although, at 35°C, τ(M) is comparable for the two neutral agents and an order of magnitude longer than that for Gd-DTPA2-, the 1/T1 NMRD profiles of Gd-DTPA-BMEA are indistinguishable from those of Gd-DTPA2- and Gd-DTPA-BMA. A 40% increase in the value of τ(SO) from Gd- DTPA2- is required for agreement of data and theory for Gd-DTPA-BMEA. CONCLUSIONS. Based on their 1/T1 NMRD profiles, the efficacy of the three agents should be identical in typical clinical MRI applications. The data can be fit reliably to theory, and differences in the fit parameters (and structure) have no effect on the three profiles at 35°C. The relatively long values of τ(M) for the two neutral agents would only be of importance at low temperatures.