Volume 59, Issue 6 pp. 2414-2419
Research Article

A Class of FeIII Macrocyclic Complexes with Alcohol Donor Groups as Effective T1 MRI Contrast Agents

Eric M. Snyder

Eric M. Snyder

Department of Chemistry, University at Buffalo, State University of New York, Amherst, New York, 14260 USA

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Didar Asik

Didar Asik

Department of Chemistry, University at Buffalo, State University of New York, Amherst, New York, 14260 USA

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Samira M. Abozeid

Samira M. Abozeid

Department of Chemistry, University at Buffalo, State University of New York, Amherst, New York, 14260 USA

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Ariel Burgio

Ariel Burgio

Department of Chemistry, University at Buffalo, State University of New York, Amherst, New York, 14260 USA

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Gage Bateman

Gage Bateman

Department of Chemistry, University at Buffalo, State University of New York, Amherst, New York, 14260 USA

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Steven G. Turowski

Steven G. Turowski

Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, 14263 USA

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Dr. Joseph A. Spernyak

Dr. Joseph A. Spernyak

Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, 14263 USA

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Prof. Dr. Janet R. Morrow

Corresponding Author

Prof. Dr. Janet R. Morrow

Department of Chemistry, University at Buffalo, State University of New York, Amherst, New York, 14260 USA

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First published: 14 November 2019
Citations: 59

Graphical Abstract

High-spin iron(III) complexes with an open coordination site for solvent interactions are effective T1 MRI contrast agents in phantoms and in live mice. A coordinated water ligand and the deprotonation of a pendant alcohol stabilize the trivalent iron center to produce strong second-sphere water interactions.

Abstract

Early studies suggested that FeIII complexes cannot compete with GdIII complexes as T1 MRI contrast agents. Now it is shown that one member of a class of high-spin macrocyclic FeIII complexes produces more intense contrast in mice kidneys and liver at 30 minutes post-injection than does a commercially used GdIII agent and also produces similar T1 relaxivity in serum phantoms at 4.7 T and 37 °C. Comparison of four different FeIII macrocyclic complexes elucidates the factors that contribute to relaxivity in vivo including solution speciation. Variable-temperature 17O NMR studies suggest that none of the complexes has a single, integral inner-sphere water that exchanges rapidly on the NMR timescale. MRI studies in mice show large in vivo differences of three of the FeIII complexes that correspond, in part, to their r1 relaxivity in phantoms. Changes in overall charge of the complex modulate contrast enhancement, especially of the kidneys.

Conflict of interest

J.R.M. is a co-founder of a company for iron contrast agents.

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