Superparamagnetic iron oxide: Pharmacokinetics and toxicity

R. Weissleder, D. D. Stark, B. L. Engelstad, B. R. Bacon, C. C. Compton, D. L. White, P. Jacobs, J. Lewis

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Abstract

The pharmacokinetics (distribution, metabolism, bioavailability, excretion) and toxicity (acute and subacute toxicity, mutagenicity) of a superparamagnetic iron oxide preparation (AMI-25), currently used in clinical trials, were evaluated by 59Fe radiotracer studies, measurements of relaxation times, the ability to reverse iron deficiency anemia, histologic examination, and laboratory parameters. One hour after administration of AMI-25 to rats (18 μmol Fe/kg; 1 mg Fe/kg), 82.6 ± 0.3% of the administered dose was sequestered in the liver and 6.2 ± 7.6% in the spleen. Peak concentrations of 59Fe were found in liver after 2 hr and in the spleen after 4 hr. 59Fe slowly cleared from liver (half-life, 3 days) and spleen (half-life, 4 days) and was incorporated into hemoglobin of erythrocytes in a time-dependent fashion. The half-time of the T2 effect on liver and spleen (24-48 hr) was shorter than the 59Fe clearance, indicating metabolism of AMI-25 into other forms of iron. IV administration of AMI-25 (30 mg Fe/kg) corrected iron-deficiency anemia and showed bioavailability similar to that of commercially available IV iron preparations within 7 days. No acute or subacute toxic effects were detected by histologic or serologic studies in rats or beagle dogs who received a total of 3000 μmol Fe/kg, 150 times the dose proposed for MR imaging of the liver. Our results indicate that AMI-25 is a fully biocompatible potential contrast agent for MR.

Original languageEnglish (US)
Pages (from-to)167-173
Number of pages7
JournalAmerican Journal of Roentgenology
Volume152
Issue number1
DOIs
StatePublished - Jan 1 1989
Externally publishedYes

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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    Weissleder, R., Stark, D. D., Engelstad, B. L., Bacon, B. R., Compton, C. C., White, D. L., Jacobs, P., & Lewis, J. (1989). Superparamagnetic iron oxide: Pharmacokinetics and toxicity. American Journal of Roentgenology, 152(1), 167-173. https://doi.org/10.2214/ajr.152.1.167