Federal grant · project grant (b)
Mri Contrast Agents Based on Iron as Alternatives to Gadolinium Agents. - Abstract/summary Iron Coordination Complexes Are Under Development as Alternatives to Gadolinium-based Mri Contrast Agents (GBCA) to Address the Concerns of GD Retention in Human Bone and Tissue. the Important Role of Iron in Human Biology, the Abundance of the Element, and Its Excellent Properties as a Relaxation Agent Make It an Important Alternative. Yet, the Development of Iron Agents Has Lagged Well Behind That of Manganese Alternatives, Due to the Challenges of Iron Coordination Chemistry. We Have Developed Innovative Solutions to Iron-based Contrast Agents Featuring Macrocyclic Ligands That Stabilize a High-spin Trivalent Iron Center (fe(iii)) as Required for a T1 Relaxation Agent. Our Lead Compounds Are Overall Anionic in Charge and Clear Rapidly Through a Renal Pathway in Mice. in This Effort, We Propose to Develop Fe(iii) Macrocyclic Complexes That Contain an Inner-sphere Water Ligand With Anionic Pendants That Produce Complexes That Are Highly Soluble in Aqueous Solution. Both Mononuclear and Dinuclear Analogs of the Iron Complexes Will Be Prepared Through the Addition of Protected, Sulfonated Pendant Groups to the Macrocyclic Framework. the Iron Complexes Will Be Further Studied as Contrast Agents in Healthy Mice. the Pharmacokinetic Clearance of the Contrast Agents Will Be Tracked Through T1 Weighted Imaging. Enhanced Contrast Produced by the Iron Complexes in Comparison to Gd(dota), as an Example of a Commonly Used Gbca, Will Be Recorded as an Important Benchmark. the Most Promising Iron Complexes Will Be Labeled With a Stable But Rare Isotope, 57FE, to Track the Retention of Iron in Mice Over Several Days, as an Important Component of Contrast Agent Development. the Maximum Tolerated Dose at 7 Days and 14 Days for Lead Complexes Will Be Studied in Mice.
Committed
$305,253
Paid out
$154.3K
51%
Committed, not yet paid
$150.9K
49%
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