Biodegradable macromolecular blood pool contrast agents

University Of Utah, Salt Lake City UT

Investigators

Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): [unreadable] The main aim of this research is to design and develop safe, effective magnetic resonance imaging (MRI) blood pool contrast agents based on biodegradable macromolecular gadolinium(Ill) complexes. It has been demonstrated in the last decade that macromolecular Gd(lll) complexes are superior blood pool contrast agents to the low molecular weight contrast agents currently used clinically. However, the macromolecular blood pool contrast agents under current development are non-degradable and are limited for further clinical development due to potential toxic effects resulting from their long body retention time. We propose to develop biodegradable macromolecular blood pool contrast agents that are stable for an acceptable period in the blood plasma for MR imaging and can be gradually degraded after the MRI examination by the biomolecules in the plasma into smaller molecules that can be cleared from the body by renal glomerular filtration. The specific aims are to design, synthesize and characterize biodegradable macromolecular Gd(lll) complexes; to determine the relaxivities and NMRD of these complexes as well as explore the impact of various physical parameters on the relaxivity of the complexes; to evaluate the safety, degradability, pharmacokinetics and long-term gadolinium tissue accumulation of the complexes; to investigate the contrast enhancement of vascular imaging and tumor imaging by the blood pool agents and their properties in measuring microvascular permeability and vascularity of solid tumors in animal models with conventional and dynamic MRI. A lead agent with the greatest image contrast enhancement and minimal Gd tissue accumulation will be selected for further development as a blood pool contrast agent. The novel blood pool agents will overcome the problems of slow clearance and deposition of gadolinium in tissues. The new technology will facilitate the clinical development of macromolecular contrast agents without molecular weight limitation. The novel blood pool contrast agents will have applications in diagnosis of the diseases in the vascular system and cancer detection and staging with MRI. The technology can also be used in the development of biodegradable diagnostic agents in other imaging modalities, including computer tomography and nuclear imaging, etc. [unreadable] [unreadable]