MnDPDP: Contrast Agent for Imaging and Protection of Viable Tissue

Abstract

The semistable chelate manganese (Mn) dipyridoxyl diphosphate (MnDPDP, mangafodipir), previously used as an intravenous (i.v.) contrast agent (Teslascan™, GE Healthcare) for Mn-ion-enhanced MRI (MEMRI), should be reappraised for clinical use but now as a diagnostic drug with cytoprotective properties. Approved for imaging of the liver and pancreas, MnDPDP enhances contrast also in other targets such as the heart, kidney, glandular tissue, and potentially retina and brain. Transmetallation releases paramagnetic Mn2+ for cellular uptake in competition with calcium (Ca2+), and intracellular (IC) macromolecular Mn2+ adducts lower myocardial T1 to midway between native values and values obtained with gadolinium (Gd3+). What is essential is that T1 mapping and, to a lesser degree, T1 weighted imaging enable quantification of viability at a cellular or even molecular level. IC Mn2+ retention for hours provides delayed imaging as another advantage. Examples in humans include quantitative imaging of cardiomyocyte remodeling and of Ca2+ channel activity, capabilities beyond the scope of Gd3+ based or native MRI. In addition, MnDPDP and the metabolite Mn dipyridoxyl diethyl-diamine (MnPLED) act as catalytic antioxidants enabling prevention and treatment of oxidative stress caused by tissue injury and inflammation. Tested applications in humans include protection of normal cells during chemotherapy of cancer and, potentially, of ischemic tissues during reperfusion. Theragnostic use combining therapy with delayed imaging remains to be explored. This review updates MnDPDP and its clinical potential with emphasis on the working mode of an exquisite chelate in the diagnosis of heart disease and in the treatment of oxidative stress.

Manganese‐Enhanced Magnetic Resonance Imaging of the Heart

“… 93 They detected decreased cellular viability and discerned the regional responses to renal artery stenosis. Early human clinical studies 94 have described visual uptake of manganese by renal tissue, but dedicated renal imaging using MEMRI has yet to be investigated.…”

Noninvasive Assessment of Kidney Injury by Combining Structure and Function Using Artificial Intelligence-Based Manganese-Enhanced Magnetic Resonance Imaging

“…As manganese (Mn) is an essential trace element for the human body, Mn-based imaging probes with excellent T1 relaxivity are good candidates for MRI to overcome the intrinsic drawbacks of Gd-based imaging agents. 33,34 Currently, a large number of Mn-based imaging probes have been developed (such as Mn chelates, MnO, MnO 2 , Mn 3 O 4 , Mndoped nanoparticles (NPs), etc. ), some of which were metabolized by the kidneys and were therefore mainly useful for structural imaging of the kidneys.…”

“…As manganese (Mn) is an essential trace element for the human body, Mn-based imaging probes with excellent T1 relaxivity are good candidates for MRI to overcome the intrinsic drawbacks of Gd-based imaging agents. , Currently, a large number of Mn-based imaging probes have been developed (such as Mn chelates, MnO, MnO 2 , Mn 3 O 4 , Mn-doped nanoparticles (NPs), etc. ), some of which were metabolized by the kidneys and were therefore mainly useful for structural imaging of the kidneys. ,,− In addition, nanoscale agents like Mn-based nanoprobes have the advantages of relatively long blood circulation in vivo and slow metabolism through the kidneys, which can greatly reduce the burden on the kidneys. − ,, Therefore, renal-clearable Mn-based nanoprobes have great potential for the noninvasive assessment of the structure and function of kidney diseases, but few studies have been reported so far.…”

VHPKQHR Peptide Modified Ultrasmall Paramagnetic Iron Oxide Nanoparticles Targeting Rheumatoid Arthritis for T1-Weighted Magnetic Resonance Imaging

“…Commonly used clinical T 1 contrast agents include Gd-DTPA (gadopentetate meglumine) ( Carr et al, 1984 ), Gd-DOTA (Dotarem) ( Meyer et al, 1988 ), and other Gd-type contrast agents, and Mn-DPDP (mangafodipir) ( Jynge et al, 2020 ), MnCl 2 , and other Mn contrast agents. However, these contrast agents are not selective, and Gd-based contrast agents may be nephrotoxic ( Prince et al, 2008 ).…”