Iron-based second-sphere contrast agents for magnetic resonance imaging: development of a model system and evaluation of iron (III) tris (tironate) complex in rats.
OBJECTIVE
Iron(III) complexes have been developed as magnetic resonance (MR) contrast agents based on the use of ligands capable of providing coordinative saturation at iron and allowing the second-sphere hydrogen bonding of water molecules.


METHODS
Studies of solution-phase binding of a probe ion to a diamagnetic metal catecholate complex and molecular orbital calculations were performed. R1 values were determined. Toxicity studies of iron(III) tris(tironate) were conducted with rats. Excretion studies were performed by analysis of urine samples. MR measurements were made.


RESULTS
Second-sphere coordination of a probe ion to a metal catecholate complex occurred in solution. Molecular orbital calculations suggested flexibility in design. Iron(III) tris (catecholate) complexes were shown to have high R1 values. Images of the kidneys and liver showed dose-dependent enhancement in T1-weighted images. The onset of toxicity was at approximately 0.30 mmol/kg. Urine analysis indicated essentially complete clearance (0.1-0.2 mmol/kg) within 24-48 hours.


CONCLUSIONS
Interactions between water molecules and basic sites within a paramagnetic metal-ligand complex allow for application of suitable complexes as T1 agents.
Davies
J A
JA
Department of Chemistry, University of Toledo, OH 43606, USA.
Dutremez
S G
SG
Hockensmith
C M
CM
Keck
R
R
Richardson
N
N
Selman
S
S
Smith
D A
DA
Ulmer
C W
CW
Wheatley
L S
LS
Zeiss
J
J
D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000633:toxicity; D000818:Animals; D003287:Contrast Media / Q000633:toxicity; D005290:Ferric Compounds / Q000633:toxicity; D019786:Gadolinium DTPA; D007668:Kidney / Q000033:anatomy & histology; D008099:Liver / Q000033:anatomy & histology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009942:Organometallic Compounds; D004369:Pentetic Acid / Q000031:analogs & derivatives; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley
D003287:Contrast Media; D005290:Ferric Compounds; D009942:Organometallic Compounds; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D004369:Pentetic Acid; D019786:Gadolinium DTPA