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Physical, chemical, and biological evaluations of P760: A new gadolinium complex characterized by a low rate of interstitial diffusion
Author(s) -
Corot Claire,
Port Marc,
Raynal Isabelle,
Dencausse Anne,
Schaefer Michel,
Rousseaux Olivier,
Simonot Christian,
Devoldere Ludovic,
Lin Jin,
Foulon Marc,
Bourrinet Philippe,
Bonnemain Bruno,
Meyer Dominique
Publication year - 2000
Publication title -
journal of magnetic resonance imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.563
H-Index - 160
eISSN - 1522-2586
pISSN - 1053-1807
DOI - 10.1002/(sici)1522-2586(200002)11:2<182::aid-jmri16>3.0.co;2-5
Subject(s) - gadolinium , chemistry , extravasation , dota , magnetic resonance imaging , vascular permeability , nuclear magnetic resonance , permeability (electromagnetism) , diffusion , chelation , nuclear medicine , biophysics , membrane , medicine , pathology , radiology , biochemistry , organic chemistry , physics , biology , thermodynamics
An original gadolinium chelate, termed P760, which diffuses through the vascular endothelium but at a much lower rate than nonspecific agents (NSA), is described. P760 is a gadolinium macrocyclic compound based on a DOTA structure that is substituted by hydrophilic bulky groups branched on the amino‐carboxylic residues.The molecular weight is 5293, and the molecular volume, measured by light scattering, is 30 times higher (11.5 nm 3 ) than that of gadolinium (Gd)‐DOTA (0.38 nm 3 ). The increase in molecular volume and weight has two consequences: a) higher relaxivity (r1; 24.7 mM −1 • s −1 compared with 3.4 mM −1 • s −1 for Gd‐DOTA at 20 Mhz, 37°C); and b) a lengthening of its transport rate through the endothelium. P760 presents a peculiar pharmacokinetic profile: at early times post injection, the blood concentrations are higher than those of Gd‐DOTA, but after 20 minutes, the blood concentrations are equal for the two compounds. The body clearances of the products are identical (ie, glomerular filtration rate). P760 molecules are large enough to have a restricted diffusion through the endothelium but, conversely, small enough to pass freely through the glomerular membrane. This limited extravasation has been observed in rabbits by magnetic resonance angiography or in investigations of tumor permeability. Further experimental imaging studies are needed to define the clinical interest of such properties. J. Magn. Reson. Imaging 2000;11:182–191. © 2000 Wiley‐Liss, Inc.