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STTR Phase I: Relaxivity mechanisms of Fe(III) MRI contrast agents

Award Information
Agency: National Science Foundation
Branch: N/A
Contract: 1746556
Agency Tracking Number: 1746556
Amount: $225,000.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: BM
Solicitation Number: N/A
Solicitation Year: 2017
Award Year: 2018
Award Start Date (Proposal Award Date): 2018-01-01
Award End Date (Contract End Date): 2018-12-31
Small Business Information
Baird Research Park 1576 Sweet Home Road
Amherst, NY 14228
United States
DUNS: 080689907
HUBZone Owned: No
Woman Owned: Yes
Socially and Economically Disadvantaged: No
Principal Investigator
 Patrick Burns
 (518) 929-5825
Business Contact
 Patrick Burns
Phone: (518) 929-5825
Research Institution
 SUNY at Buffalo
 Janet Morrow
 Nonprofit College or University

This STTR Phase I project will undertake the development of iron coordination complexes as alternatives for gadolinium contrast agents which are currently used in clinical MRI diagnostic exams. New MRI contrast agents are needed to serve the segment of the population who cannot tolerate Gd(III) agents. This includes patients with kidney disease and those who have frequent MRI scans and may accumulate Gd(III). The proposed research involves the study of new trivalent iron coordination complexes based on those initially studied in the co-PI?s university laboratory. New iron complexes will be prepared and studied as contrast agents in live mice to improve characteristics of the agents such as clearance from the body. Fundamental studies of the iron complexes will add to the body of knowledge on the paramagnetic properties of iron. For the most promising Fe(III) contrast agents, the synthetic procedures will be adapted for large scale preparation and purity determination. Iron MRI contrast agents may also be beneficial to society by reducing gadolinium in water supply. Furthermore, iron as an abundant element is less expensive and more readily available in the USA than is gadolinium. The commercialization of iron MRI contrast agents will create jobs in chemical manufacturing, sales, and in health-related occupations. The lead Fe(III) coordination complex on which this project is based produces longitudinal (T1) relaxivity of water protons that rival clinically used Gd(III) complexes at 4.7 Tesla, both under in vitro conditions and also in live mice. Importantly, these complexes contain macrocyclic ligands that stabilize iron in the trivalent state (negative redox potentials versus NHE) and do not produce reactive oxygen species even in the presence of ascorbate as a reductant and peroxide. The importance of outersphere water and innersphere water interactions will be studied by varying the coordinating pendent groups on the macrocyclic ligand which is bound to Fe(III). The ancillary group will be varied to increase binding to serum proteins and to modify the clearance route of the contrast agents either through kidneys or through hepatobiliary routes. The complexes will be optimized for kinetic inertness towards release of iron under biologically relevant conditions. Toxicity studies in cell culture will be carried out on each of the new complexes. This research will focus on both pilot scale preparation for the study of the Fe(III) complexes in vitro and also on larger scale preparations and HPLC analysis of the most promising new derivatives. In vivo MRI scans in mice on a 4.7 T scanner will be used to track the distribution and clearance of the iron contrast agents as a function of time.

* Information listed above is at the time of submission. *

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