Available Technology

Superior Method of Preparing Dendrimers for Use as Magnetic Resonance Imaging (MRI) Contrast Agents

There is a need to develop more efficient gadolinium-containing (Gd) contrast agents for magnetic resonance imaging (MRI) as the small molecules presently used clinically have the disadvantage of being rapidly cleared from circulation and excreted by the kidneys.

Dendrimer-based macromolecular MRI contrast agents in which numerous chelated Gd ions are covalently attached to a multivalent dendritic architecture are a promising class of diagnostic agents for medical imaging applications. Clinical development of the dendrimer-based agents has been limited as the current methods for synthesizing them result in a complex mixture that produces inconsistent imaging results.

The present technology describes the development of a new method of pre-forming the metal-ligand chelate in alcohol prior to conjugation to the dendrimer. Specifically, for example, a 1B4M-DTPA-Gd chelate is preformed in methanol and purified prior to conjugation to a PAMAM dendrimer molecule. This results in a dendrimer-based MRI contrast agent with greatly improved homogeneity and stability, and possessing an unexpectedly greater molar relaxivity that allows the use of much less of the agent than previously required to obtain comparable images. The use of a DOTA-Gd chelate is equally possible.

Patent Abstract: 

There is a need to develop more efficient gadolinium-containing (Gd) contrast agents for magnetic resonance imaging (MRI) as the small molecules presently used clinically have the disadvantage of being rapidly cleared from circulation and excreted by the kidneys.

Dendrimer-based macromolecular MRI contrast agents in which numerous chelated Gd ions are covalently attached to a multivalent dendritic architecture are a promising class of diagnostic agents for medical imaging applications. Clinical development of the dendrimer-based agents has been limited as the current methods for synthesizing them result in a complex mixture that produces inconsistent imaging results.

The present technology describes the development of a new method of pre-forming the metal-ligand chelate in alcohol prior to conjugation to the dendrimer. Specifically, for example, a 1B4M-DTPA-Gd chelate is preformed in methanol and purified prior to conjugation to a PAMAM dendrimer molecule. This results in a dendrimer-based MRI contrast agent with greatly improved homogeneity and stability, and possessing an unexpectedly greater molar relaxivity that allows the use of much less of the agent than previously required to obtain comparable images. The use of a DOTA-Gd chelate is equally possible.

Benefits 
Efficient preparation of stable dendrimer-based contrast agents suitable for medical imaging -Higher molar relaxivity translates into a lower dosage needed for imaging -Ability to control dendrimer size conducive for development of compartment-specific imaging agents
Inventors: 

Kido Nwe

Patent Number: 
61180,327
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