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

The broader/commercial impact of this Small Business Technology Transfer (STTR) Phase II project will focus on the preparation of new iron-based compounds as safer contrast agents for magnetic resonance imaging (MRI), an issue that particularly affects patients who have frequent MRI scans and those with chronic kidney disease. This project will advance the development of safer medical imaging. This STTR Phase II project will focus on further development of the first Fe(III) macrocycle-based T1 MRI contrast agents as alternatives to Gd(III) agents. The macrocyclic ligands in these complexes are used to control the spin and oxidation state of the iron, as well as the biodistribution and pharmacokinetic clearance of the agent. The macrocyclic ligands will be modified to further increase T1 relaxivity of the Fe(III) complexes. The hydrophicility of the complexes will be increased to better mimic the clearance profiles of Gd(III) based agents. Scale-up of the synthetic procedures will produce sufficient compound batches for toxicity studies in mice, including the maximum tolerated dose (MTD) and the no adverse effect level (NOAEL), imaging studies in rats, as well as histology and metabolic panels. The most promising complexes will be subjected to further toxicity studies including Ames testing, thymidine kinase cell screens and cardiotoxicity assays. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.