A Manganese-based Alternative to Gadolinium: Contrast-enhanced MR Angiography, Excretion, Pharmacokinetics, and Metabolism

Purpose: To compare intravascular contrast enhancement produced by the manganese-based magnetic resonance (MR) imaging contrast agent manganese-N-picolyl-N, N', N'-trans-1,2-cyclohexenediaminetriacetate (Mn-PyC3A) to gadopentetate dimeglumine (Gd-DTPA) and to evaluate the excretion, pharmacokinetics, and metabolism of Mn-PyC3A. Materials and Methods: Contrast material-enhanced MR angiography was performed in baboons (Papio anubis; n = 4) by using MnPyC3A and Gd-DTPA. Dynamic imaging was performed for 60 minutes following Mn-PyC3A injection to monitor distribution and elimination. Serial blood sampling was performed to quantify manganese and gadolinium plasma clearance by using inductively coupled plasma mass spectrometry and to characterize Mn-PyC3A metabolism by using high-performance liquid chromatography. Intravascular contrast enhancement in the abdominal aorta and brachiocephalic artery was quantified by measuring contrast- to-noise ratios (CNRs) versus muscle at 9 seconds following Mn-PyC3A or Gd-DTPA injection. Plasma pharmacokinetics were modeled with a biexponential function, and data were compared with a paired t test. Results: Aorta versus muscle CNR (mean 6 standard deviation) with Mn-PyC3A and Gd-DTPA was 476 6 77 and 538 6 120, respectively (P =.11). Brachiocephalic artery versus muscle CNR was 524 6 55 versus 518 6 140, respectively (P =.95). Mn-PyC3A was eliminated via renal and hepatobiliary excretion with similar pharmacokinetics to GdDTPA (area under the curve between 0 and 30 minutes, 20.2 +/- 3.1 and 17.0 +/- 2.4, respectively; P =.23). High-performance liquid chromatography revealed no evidence of Mn-PyC3A biotransformation. Conclusion: Mn-PyC3A enables contrast-enhanced MR angiography with comparable contrast enhancement to gadoliniumbased agents and may overcome concerns regarding gadolinium- associated toxicity and retention.