Ricardo Gonzalez-Mendez PhD, Presenter: Co-founder, Fe8 Inc Co-owner, Fe8 Inc

Soma Das BS, Abstract Co-Author: Nothing to Disclose

Indranil Chakrabirty PhD, Abstract Co-Author: Nothing to Disclose

Rapahel Raptis PhD, Abstract Co-Author: Co-founder, Fe8 Inc Co-owner, Fe8 Inc

We have designed new Fe-based nanocluster molecule using a Fe8(μ4-O)4 motif found in minerals in nature. These molecules have the physical characteristics to be potential MRI contrast agents.

Directly water-soluble [Fe8(μ4-O)4(μ-4-R-pz)12X4] complexes have been prepared containing either R or X hydrophilic groups. The compound [Fe8(μ4-O)4(μ-pz)12(O-mld)4], where O-mld = N-hydroxymaleimide anion, has been prepared from the parent [Fe8(μ4-O)4(μ-pz)12Cl4] by a ligand substitution reaction. The reaction is carried out in an organic solvent (THF, CH2Cl2) in which the chloro compound is soluble and the oxo-maleimido product is not. This facilitates the isolation of [Fe8(μ4-O)4(μ-pz)12(O-mld)4] as a dry dark red powder under N2 atmosphere. T1 and T2 measurements were carried out at 7 T and 11.7 T using Bruker NMR spectrometers and an inversion recovery sequence for T1 measurement, and a CPMG spin-echo sequence for T2 measurements Data was anlyzed with SigmaPlot. Standard T1-weighted and T2-weighted imaging protocols were used for phantom imaging using TRs 100-800 for T1 weighted imaging, and TRs of 1500-3000 for T2 weighted imaging at 1.5 T. Images were analyzed with OsiriX.

We have been able to isolate a discrete Fe8-cluster, [Fe8(μ4-O)4(μ-pz)12Cl4], where pz = pyrazolato anion. This cluster has a diameter of approximately 1.2 nm and an effective magnetic moment of μ = 7.0 B.M., comparable to that of Gd3+ ions. The MRI properties of our Fe8 complexes have been evaluated by T1 and T2 determination. A clinical Gd-based agent, OptiMARK® (Mallinckrodt), was used for direct comparison with our compounds. The T1-relaxivity of OptiMARK, the fastest relaxing CA in current clinical use, is r1 = 4.1 s-1mM-1 at 15 T. In the same magnetic field, r1 for the directly water-soluble [Fe8(μ4-O)4(μ-pz)12(mld)4], r1 = 9.8 s-1mM-1. We have determined a contrast-to-noise ratio of approximately 250 for various Fe8 solutions.

We have a new family of compounds with both excellent T1 and T2 contrast, an important advantage when compared to existing compounds as it might be possible to get both positive and negative contrast enhancement from the Fe8 nanoclusters.

We have developed a new class of iron-based nanomolecules with excellent relaxivity characteristics that have great promise as MRI contrast agents.

Gonzalez-Mendez, R, Das, S, Chakrabirty, I, Raptis, R, Development and Characterization of [Fe8(μ4-O)4(μ-4-R-pz)12X4]: A New Class of Iron-based Nanoclusters with Potential as MRI Contrast Agent.  Radiological Society of North America 2009 Scientific Assembly and Annual Meeting, November 29 - December 4, 2009 ,Chicago IL. http://archive.rsna.org/2009/8013974.html