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New multimeric magnetic resonance imaging agents

R S Ranganathan¹, M E Fernandez, S I Kang

¹Bracco Research USA, Princeton, New Jersey 08540, USA. rrangana@research.bracco.com

Investigative Radiology

|November 18, 1998

Summary

Multimerization of gadolinium chelates enhances MRI contrast agent relaxivity with increasing molecular weight. Modulating water relaxation times is key for developing advanced agents for biochemical process imaging.

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Area of Science:

Materials Science
Biochemistry
Medical Imaging

Background:

Developing sensitive magnetic resonance imaging (MRI) contrast agents is crucial for studying biochemical processes.
Macrocyclic gadolinium (Gd) chelates are widely used as MRI contrast agents.

Purpose of the Study:

To investigate the effect of multimerization on the relaxivity of macrocyclic gadolinium chelates.
To develop more sensitive MRI contrast agents for biochemical imaging.

Main Methods:

Synthesized covalently linked nonionic, macrocyclic, multimeric lanthanide chelates (dimers to octamers, 1-5 KDa).
Utilized amide or 2-hydroxypropylidene bonds for chemical linkage.
Determined relaxivity (r1) for Gd3+ chelates and hydration numbers (Q) for Tb3+ chelates.

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Main Results:

Relaxivity (r1) increased with molecular weight, attributed to increased rotational correlation time (τr).
Hydration numbers (Q) remained unaffected by multimerization.
Amide-based chelates showed higher r1 values than hydroxyl-based chelates due to differences in water exchange time (τm).

Conclusions:

Molecular weight and linker rigidity significantly influence MRI contrast agent relaxivity.
Modulating water relaxation time (τm) is essential for future functional MRI contrast agent development.
Optimized multimeric chelates hold promise for enhanced biochemical process imaging.