title: Influence of iron chelation on R1 and R2 calibration curves in gerbil liver and heart.
abstract: MRI is gaining increasing importance for the noninvasive quantification of organ iron burden. Since transverse relaxation rates depend on iron distribution as well as iron concentration, physiologic and pharmacologic processes that alter iron distribution could change MRI calibration curves. This article compares the effect of three iron chelators, deferoxamine, deferiprone, and deferasirox, on R1 and R2 calibration curves according to two iron loading and chelation strategies. Thirty-three Mongolian gerbils underwent iron loading (iron dextran 500 mg/kg/wk) for 3 weeks followed by 4 weeks of chelation. An additional 56 animals received less aggressive loading (200 mg/kg/week) for 10 weeks, followed by 12 weeks of chelation. R1 and R2 calibration curves were compared to results from 23 iron-loaded animals that had not received chelation. Acute iron loading and chelation-biased R1 and R2 from the unchelated reference calibration curves but chelator-specific changes were not observed, suggesting physiologic rather than pharmacologic differences in iron distribution. Long-term chelation deferiprone treatment increased liver R1 50% (P < 0.01), while long-term deferasirox lowered liver R2 30.9% (P < 0.0001). The relationship between R1 and R2 and organ iron concentration may depend on the acuity of iron loading and unloading as well as the iron chelator administered.
authors.affiliation: Division of Pediatric Cardiology, Children's Hospital Los Angeles, 4650 Sunset Boulevard, Los Angeles, CA 90027, USA. jwood@chia.usc.edu
authors.forename: John C
authors.initials: JC
authors.lastname: Wood
authors.forename: Michelle
authors.initials: M
authors.lastname: Aguilar
authors.forename: Maya
authors.initials: M
authors.lastname: Otto-Duessel
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Nick
authors.forename: Marvin D
authors.initials: MD
authors.lastname: Nelson
authors.forename: Rex
authors.initials: R
authors.lastname: Moats
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D000077588:Deferasirox; D000077543:Deferiprone; D003676:Deferoxamine / Q000494:pharmacology; D005849:Gerbillinae; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology; D008099:Liver / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D009206:Myocardium / Q000737:chemistry*; D011728:Pyridones / Q000494:pharmacology; D017262:Siderophores / Q000494:pharmacology; D014018:Tissue Distribution; D014230:Triazoles / Q000494:pharmacology
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D011728:Pyridones; D017262:Siderophores; D014230:Triazoles; D000077543:Deferiprone; D007501:Iron; D003676:Deferoxamine; D000077588:Deferasirox