A toxicologic risk for using manganese complexes? A literature survey of existing data through several medical specialties.
This article summarizes data from the literature about biologic functions, toxicity, and biokinetics of manganese to help the reader assess the importance of complex stability of manganese-based contrast agents. Free manganese may present a greater risk than free gadolinium, especially because it has a physiologic role and can therefore trigger multiple functions. Of particular interest are the deleterious effects of manganese on the central nervous system (it can cross the intact blood-brain barrier) and on developing life (it penetrates the placental barrier as well and is teratogenic). After intravenous contrast injection, normal (enteral) regulation mechanisms for manganese homeostasis are bypassed, and there is a danger of individual overdosing. Excess manganese, for example in patients with chronic liver disease or with chronic parenteral nutrition, has already been detected by magnetic resonance imaging in the basal ganglia and was found to coincide with neurologic symptoms. Decomplexation with release of free manganese substantially prolongs the elimination of the metal because manganese can be excreted only slowly via the biliary system. This may be of particular importance in patients with impaired hepatic function. Although minimal amounts of free manganese ions are not considered harmful to the human body, significant decomplexation of manganese complexes will require careful analysis of the diagnostic benefit versus the potential risk posed by the free metal ions.
Misselwitz
B
B
Research Laboratories of Schering AG, Berlin, Germany.
Mühler
A
A
Weinmann
H J
HJ
D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D001812:Blood-Brain Barrier; D003287:Contrast Media / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity*; D006706:Homeostasis; D006801:Humans; D008107:Liver Diseases / Q000378:metabolism; D008345:Manganese / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D020149:Manganese Poisoning; D010288:Parenteral Nutrition; D010920:Placenta / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D013723:Teratogens / Q000494:pharmacology
D003287:Contrast Media; D013723:Teratogens; D008345:Manganese