NEW MULTIMERIC MAGNETIC-RESONANCE-IMAGING AGENTS

RATIONALE AND OBJECTIVES. The authors investigated the effect of multi merization on the relaxivity of macrocyclic gadolinium (Gd) chelates, The objective was to develop more sensitive magnetic resonance imaging (MRI) contrast agents to study biochemical processes. METHODS. Covale ntly linked nonionic, macrocyclic, multimeric lanthanide chelates that belong to the classes of dimers, trimers, tetramers, hexamer, and oct amer, in the molecular weight range similar to 1 to 5 KDa, were synthe sized. The chemical linkage was based on either the a;nide bond or the 2-hydroxypropylidene bond. Relaxivity values, (20)r(1), on Gd3+ chela tes and hydration numbers, Q, on Tb3+ chelates were determined. RESULT S. Relaxivity values increased with molecular weight and Q values were not affected. the increase in r(1) is attributable to the expected in crease in the overall rotational correlation time, tau(r) with an incr ease in molecular weight. The rigidity of the linkers, which is expect ed to affect the intrachelate rotational: correlation time tau(r) tha t makes a contribution to the overall correlation time, tau(r), exerte d a noticeable effect. The hydroxyl-based chelates generally had lower r(1) values than the amide-based chelates, This is rationalized as ar ising from the longer and thereby rate-limiting effect of the tau(m) v alue for the hydroxyl chelates compared with that reported of the amid e-based chelates, This rate limiting effect of tau(m) becomes a domina nt factor controlling attainable enhanced relaxivity when multimers ba sed on traditional chelate designs are used for MRI applications. CONC LUSIONS. Approaches aimed at enhancing relaxivity by modulating the wa ter relaxation time, tau(m), will be important for the future developm ent of functional MRI contrast agents for the imaging of biochemical p rocesses.