General toxicology of MnDPDP

Abstract

Purpose:To investigate the general toxicology of mangafodipir trisodium (Mn-DPDP, Teslascan).Material and Methods: Studies were performed in accordance with standard methods and in compliance with regulations current at the time of conduct.Results: Single-dose studies in rodents and dogs showed that MnDPDP was tolerated at doses of approximately 2000 ymolkg, approximately 400 times a single imaging dose of 5 pmoVkg. The single dose tolerance of MnDPDP was approximately 10 times greater than MnC1,. A good safety profile of MnDPDP was also shown in repeat-dose studies (3 weeks), in which the no-observed-adverse-effect level for the rat, monkey and dog was 116,29 and 10 ymoVkg, respectively. The local tolerance studies indicated that no adverse local tissue reactions are likely to occur after i.v. injection. Other studies indicate that accidental spillage of MnDPDP onto the skin is not expected to lead to significant systemic exposure, or to local irritation or hypersensitivity. MnDPDP was not genotoxic in a battery of several different tests.Conclusion: MnDPDP was shown to have a good safety profile suitable as an hepatobiliary MR contrast agent for i.v. administration. ommended daily allowance for adults of 2-5 mg (46). The purpose of this paper is to summarize several of the general toxicology studies on MnDPDP, including single and repeat-dose studies, genetic toxicology, local tolerance, antigenicity and skin permeability which, together with other pre-clinical and clinical data (17,28,31,33,45,62,64,67), aims to provide a sufficiently detailed toxicological profile of MnDPDP for an objective assessment of safety.

Metal-Based Complexes as Pharmaceuticals for Molecular Imaging of the Liver

“…Also, possible adverse cardiovascular responses such as negative inotropy and vasodilation were suspected to occur based on the fact that Mn(II)—particularly if released at high extracellular concentrations—may act as a clinically-relevant Ca(II) antagonist [88,108,109]. However, early studies focused on toxicity and cardiovascular effects have concluded that Mn-DPDP is generally safe in normal clinical use [90,110,111].…”

Manganese Based MR Contrast Agents: Formulation and Clinical Applications

“…In comparison with MnCl2, MnDPDP was shown to have a much better safety profile suitable as an hepatobiliary MR contrast agent for i.v. administration [38].…”

A new opportunity for MEMRI

“…While numerous pre-clinical studies demonstrated toxicity of MnCl 2 at high doses, MnDPDP exhibits no major toxicity in a variety of animal models at doses much higher than those required for adequate image enhancement [ 5 ]. Moreover, multiple clinical trials demonstrated tolerability to MnDPDP in human subjects.…”