Preclinical evaluation of MnDPDP: new paramagnetic hepatobiliary contrast agent for MR imaging

Radiology. 1991 Jan;178(1):73-8. doi: 10.1148/radiology.178.1.1898538.

Abstract

Manganese(II)-N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5'-bis (phosphate) (MnDPDP) is a paramagnetic complex designed for use as a hepatobiliary agent. The T1 relaxivity of MnDPDP (2.8 [mmol/L]-1.sec-1 in aqueous solution) was similar to that of gadolinium diethylenetriaminepentaacetic acid (DTPA) (4.5 [mmol/L]-1.sec-1) and gadolinium tetraazocyclodecanetetraacetic acid (DOTA) (3.8 [mmol/L]-1.sec-1). However, in liver tissue the T1 relaxivity of MnDPDP (21.7 [mmol/L]-1.sec-1) was threefold higher than that reported for Gd-DOTA (6.7 [mmol/L]-1.sec-1). Maximum liver T1 relaxation enhancement occurred 30 minutes after injection of MnDPDP, at which time 54MnDPDP biodistribution studies indicated that 13% of total body activity was in the liver. Enhanced (MnDPDP, 50 mumol/kg) MR images showed a fivefold increase in tumor-liver contrast-to-noise ratio over baseline unenhanced images. Results of the authors' acute and subchronic toxicity studies suggest that MnDPDP will be safe at the doses necessary for clinical imaging; at 10 mumol/kg, the safety factor (LD50/effective dose) for MnDPDP is 540, significantly greater than the safety factor of Gd-DTPA (ie, 60-100).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Contrast Media*
  • Dogs
  • Drug Evaluation, Preclinical
  • Edetic Acid* / toxicity
  • Female
  • Lethal Dose 50
  • Liver / anatomy & histology*
  • Magnetic Resonance Imaging*
  • Male
  • Manganese
  • Manganese Poisoning
  • Mice
  • Pyridoxal Phosphate / analogs & derivatives*
  • Pyridoxal Phosphate / toxicity
  • Rats
  • Tissue Distribution

Substances

  • Contrast Media
  • Manganese
  • Pyridoxal Phosphate
  • Edetic Acid
  • N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid