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

ABSTRACT: 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 Mn-PyC3A 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 ± standard deviation) with Mn-PyC3A and Gd-DTPA was 476 ± 77 and 538 ± 120, respectively (P = .11). Brachiocephalic artery versus muscle CNR was 524 ± 55 versus 518 ± 140, respectively (P = .95). Mn-PyC3A was eliminated via renal and hepatobiliary excretion with similar pharmacokinetics to Gd-DTPA (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 gadolinium-based agents and may overcome concerns regarding gadolinium-associated toxicity and retention. © RSNA, 2017 Online supplemental material is available for this article.

SUBMITTER: Gale EM

PROVIDER: S-EPMC5831267 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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

Gale Eric M EM Wey Hsiao-Ying HY Ramsay Ian I Yen Yi-Fen YF Sosnovik David E DE Caravan Peter P

Radiology 20171108 3

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 Mn-PyC3A and Gd-DTPA. Dynamic imaging was performed f ...[more]

PMID: 29117483

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Project description:Background and purposeThe diagnosis of spinal vascular malformations may be challenging on conventional MR imaging because neither the location of the signal abnormality in the spinal cord nor the level of the abnormal flow voids correlates with the level of the fistula. We conducted a retrospective evaluation of the utility of using a time-resolved imaging of contrast kinetics sequence in the diagnosis, characterization, and localization of spinal vascular malformations, comparing it with the criterion standard of spinal DSA.Materials and methodsFifty-five consecutive patients with a suspected diagnosis of spinal vascular malformation underwent time-resolved imaging of contrast kinetics followed by spinal DSA. All scans were performed on a 1.5T scanner by using a standard 8-channel spine coil and were reported by a neuroradiologist before the DSA was performed.ResultsForty-seven lesions were confirmed on time-resolved imaging of contrast kinetics and classified as spinal dural arteriovenous fistulas (n = 33, with 1 patient having a type Ib fistula), perimedullary spinal cord arteriovenous fistulas (n = 10), and intramedullary arteriovenous malformations (n = 3). One patient had an extradural spinal vascular malformation. Time-resolved imaging of contrast kinetics identified the location of the arterial feeder to within 1 vertebral level in 27/33 patients (81.8%) with spinal dural arteriovenous fistulas and correctly predicted the side in 22/33 (66.6%) patients. Perimedullary spinal cord arteriovenous fistulas were erroneously considered to represent spinal dural arteriovenous fistulas before spinal DSA. The anatomy of the arterial supply to intramedullary arteriovenous malformations was also poorly characterized on time-resolved contrast-enhanced MR angiography.ConclusionsIt has been our experience that time-resolved imaging of contrast kinetics is a useful confirmatory tool when a spinal vascular malformation is suspected on the basis of clinical and conventional MR imaging findings. As experience with the technique grows and sequences are refined, it may be possible to rely on time-resolved imaging of contrast kinetics as a screening tool for the diagnosis of spinal vascular malformations.

Project description:PurposeTo demonstrate that highly accelerated (net acceleration factor [R(net)] ≥ 10) acquisition techniques can be used to generate three-dimensional (3D) subsecond timing images, as well as diagnostic-quality high-spatial-resolution contrast material-enhanced (CE) renal magnetic resonance (MR) angiograms with a single split dose of contrast material.Materials and methodsAll studies were approved by the institutional review board and were HIPAA compliant; written consent was obtained from all participants. Twenty-two studies were performed in 10 female volunteers (average age, 47 years; range, 27-62 years) and six patients with renovascular disease (three women; average age, 48 years; range, 37-68 years; three men; average age, 60 years; range, 50-67 years; composite average age, 54 years; range, 38-68 years). The two-part protocol consisted of a low-dose (2 mL contrast material) 3D timing image with approximate 1-second frame time, followed by a high-spatial-resolution (1.0-1.6-mm isotropic voxels) breath-hold 3D renal MR angiogram (18 mL) over the full abdominal field of view. Both acquisitions used two-dimensional (2D) sensitivity encoding acceleration factor (R) of eight and 2D homodyne (HD) acceleration (R(HD)) of 1.4-1.8 for R(net) = R · R(HD) of 10 or higher. Statistical analysis included determination of mean values and standard deviations of image quality scores performed by two experienced reviewers with use of eight evaluation criteria.ResultsThe 2-mL 3D time-resolved image successfully portrayed progressive arterial filling in all 22 studies and provided an anatomic overview of the vasculature. Successful timing was also demonstrated in that the renal MR angiogram showed adequate or excellent portrayal of the main renal arteries in 21 of 22 studies.ConclusionTwo-dimensional acceleration techniques with R(net) of 10 or higher can be used in CE MR angiography to acquire (a) a 3D image series with 1-second frame time, allowing accurate bolus timing, and (b) a high-spatial-resolution renal angiogram.Supplemental materialhttp://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11110242/-/DC1.

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Dataset Information

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

Publications

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

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