Synthesis and preliminary evaluation of MP-2269: a novel, nonaromatic small-molecule blood-pool MR contrast agent

Magn Reson Med. 1998 Nov;40(5):733-9. doi: 10.1002/mrm.1910400514.

Abstract

A nonaromatic, small-molecule, gadolinium(3+)-chelate code named MP-2269 was synthesized and evaluated in animals as a potential MR contrast agent for blood pool. The ligand of MP-2269 was prepared by conjugating a lipophilic, albumin-binding moiety, 4-pentylbicyclo[2.2.2]octane-1-carboxylic acid, to an amino-functionalized DTPA derivative by means of a diaspartic acid linker. Proton relaxometry studies in vitro yielded spin-lattice relaxivities (R1) for MP-2269 of 6.2, 20.0 and 26.1 mM(-1)sec(-1) in water, rabbit blood, and human blood, respectively. The enhanced relaxivities in blood indicate significant binding of the agent to blood proteins. At a dose of 45 micromol/kg, MP-2269 showed a biphasic rabbit blood clearance profile with half-lives of 4.7 and 142 minutes, respectively, for the fast and slow components. In rats, the agent is cleared predominantly through the hepatobiliary pathway (approximately 70% in 24 h by this mode). The LD50 value of MP-2269 is approximately 3.0 mmol/kg in mice. Preliminary MR angiograms obtained in the rabbit showed excellent enhancement of blood vessels. Hence, MP-2269 has potential for future exploitation as a contrast agent for MR angiography.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Contrast Media / chemical synthesis
  • Contrast Media / chemistry
  • Contrast Media / pharmacology*
  • Evaluation Studies as Topic
  • Gadolinium DTPA / analogs & derivatives*
  • Gadolinium DTPA / chemical synthesis
  • Gadolinium DTPA / chemistry
  • Gadolinium DTPA / pharmacology
  • Humans
  • Lethal Dose 50
  • Magnetic Resonance Angiography / methods*
  • Mice
  • Rabbits
  • Rats
  • Sensitivity and Specificity
  • Tissue Distribution

Substances

  • Contrast Media
  • MP 2269
  • Gadolinium DTPA