title: New multimeric magnetic resonance imaging agents.
abstract: OBJECTIVE
  The authors investigated the effect of multimerization 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
  Covalently linked nonionic, macrocyclic, multimeric lanthanide chelates that belong to the classes of dimers, trimers, tetramers, hexamer, and octamer, in the molecular weight range approximately 1 to 5 KDa, were synthesized. The chemical linkage was based on either the amide bond or the 2-hydroxypropylidene bond. Relaxivity values, 20r1, on Gd3+ chelates and hydration numbers, Q, on Tb3+ chelates were determined.
  
  
  RESULTS
  Relaxivity values increased with molecular weight and Q values were not affected, the increase in r1 in attributable to the expected increase in the overall rotational correlation time, tau r with an increase in molecular weight. The rigidity of the linkers, which is expected to affect the intrachelate rotational correlation time tau r* that makes a contribution to the overall correlation time, tau r, exerted a noticeable effect. The hydroxyl-based chelates generally had lower r1 values than the amide-based chelates. This is rationalized as arising from the longer and thereby rate-limiting effect of the tau m value for the hydroxyl chelates compared with that reported of the amide-based chelates. This rate limiting effect of tau m becomes a dominant factor controlling attainable enhanced relaxivity when multimers based on traditional chelate designs are used for MRI applications.
  
  
  CONCLUSIONS
  Approaches aimed at enhancing relaxivity by modulating the water relaxation time, tau m, will be important for the future development of functional MRI contrast agents for the imaging of biochemical processes.
authors.affiliation: Bracco Research USA, Princeton, New Jersey 08540, USA. rrangana@research.bracco.com
authors.forename: R S
authors.initials: RS
authors.lastname: Ranganathan
authors.forename: M E
authors.initials: ME
authors.lastname: Fernandez
authors.forename: S I
authors.initials: SI
authors.lastname: Kang
authors.forename: A D
authors.initials: AD
authors.lastname: Nunn
authors.forename: P C
authors.initials: PC
authors.lastname: Ratsep
authors.forename: K M
authors.initials: KM
authors.lastname: Pillai
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: M F
authors.initials: MF
authors.lastname: Tweedle
mesh_terms: D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry; D005682:Gadolinium; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*
chemical_list: D003287:Contrast Media; D005682:Gadolinium