T1 efficacy of EVP‐ABD: A potential manganese‐based MR contrast agent for hepatic vascular and tissue phase imaging

Abstract

Purpose: To evaluate the T1 efficacy of EVP-ABD, a new manganese (Mn)-based contrast agent, for vascular and liver tissue enhancement in comparison with currently approved agents. Materials and Methods:Ten Yorkshire pigs (body weight, 26 -46 kg) were used for the efficacy evaluation, nine for kinetic T1 evaluation (three each agent) and one for post EVP-ABD imaging. With a fast imaging scheme to monitor T1 values of blood and liver, 10 mol/kg EVP-ABD was injected intravenously and compared with gadopentetate dimeglumine (Magnevist, GdDTPA) and mangafodipir trisodium (Teslascan, mangafodipir trisodium) at routine clinical dosages. All were imaged with 3D T1 Gradient Recalled Echo (GRE) sequence (TR/TE/␣ ϭ 3.8/1.6/25°) prior to and 10 minutes post injection using a 1.5-T whole-body scanner. Additional high-resolution 2D liver images (TR/ TE/␣ ϭ 50/4.6/40°) and arterial phase images of the upper aorta were acquired from the pig for post EVP-ABD imaging. Results:At 10 mol/kg, EVP-ABD provided a dramatic decline in blood T1, comparable to 0.1 mmol/kg GdDTPA, followed by a rapid return to blood baseline T1 values. In addition to the blood enhancement phase, EVP-ABD achieved a 70% reduction in liver T1 within 2 minutes postadministration, with an imaging window of at least 2 hours. A substantially improved signal-to-noise ratio (SNR) was observed in both the 2D and 3D liver images postcontrast.Conclusion: EVP-ABD demonstrated peak vascular enhancement similar to GdDTPA and prolonged specific liver enhancement exceeding mangafodipir trisodium. EVP-ABD has favorable T1 enhancing characteristics with the potential to allow for a comprehensive liver evaluation.

EVP‐ABD‐enhanced MRI to evaluate diffuse liver disease in a rat model

“…This and susceptibility artifacts associated with SPIO particles (11) may hinder the sensitivity of this scheme. EVP‐ABD is not a particle and is not phagocytized into Kupffer cells as SPIO particles are (8, 9); rather, like manganese chloride, it is rapidly taken up by functioning hepatocytes and secreted into bile (12, 13, 15). Mn‐enhanced MRI is a technique based on the normal function of hepatic cells and it provides prolonged positive T1 enhancement in diagnostic images.…”

“…EVP‐ABD addresses the safety of Mn pharmacologically through formulation with calcium (Ca). This approach provides enhanced safety over that seen for Mn alone while maintaining all of the magnetic and kinetic features of Mn required to achieve simultaneous vascular kinetic information and prolonged tissue enhancement by MRI (14, 15). In fact, the safety index (ratio of lethal dose to effective dose) of EVP‐ABD equals or exceeds that of the most widely used imaging agents, including gadopentetate dimeglumine and the nonionic iodinated radiographic agents (14, 38).…”

“…so can be measured when TI ≫ T1. We set TI = 7 seconds for the so measurement, considering normal liver T1 ≈0.7 seconds (15) in this study. T1 were calculated from the slope of linear least squares fit of ln(1‐s/so) versus TI plot.…”

“…It was designed for hepatic imaging and it addresses the safety of Mn pharmacologically through formulation with calcium (Ca) (14). This study was designed to quantify hepatic uptake of the Mn‐based imaging agent EVP‐ABD (14) as described previously for normal liver (15) across the full range of disease severity in an established rat hepatitis model. The degree to which uptake correlates with histology scores points to the potential for noninvasive assessment of diffuse liver disease.…”

Manganese-Enhanced Magnetic Resonance Imaging (MEMRI)

“…One such agent, available from Eagle Vision Pharmaceuticals, consists of free Mn 2+ ions formulated with Ca 2+ to override the transient effect of Mn 2+ as a Ca 2+ competitive inhibitor. This agent is currently used in dogs and pigs for cardiac (86, 87) as well as for vascular imaging (88). The development of such agent shows promise for the imminent use of Mn 2+ as a clinical contrast agent for cardiac and brain imaging.…”