General toxicology of MnDPDP

Abstract

Purpose: To investigate the general toxicology of mangafodipir trisodium (MnDPDP, 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 μmol/kg, approximately 400 times a single imaging dose of 5 μmol/kg. The single dose tolerance of MnDPDP was approximately 10 times greater than MnCl₂. 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 μmol/kg, 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.