Siauve N, Cuénod C A, Clément O, Rasio E, Bendayan M, Frija G
Laboratoire de Recherche en Imagerie, Faculté de Médecine Necker, Paris, France.
J Magn Reson Imaging. 1999 Feb;9(2):353-61. doi: 10.1002/(sici)1522-2586(199902)9:2<353::aid-jmri31>3.0.co;2-u.
Our purpose was to study the capillary leakage of MR contrast media using a pure capillary model, the rete mirabile of the eel. The rete is a countercurrent-exchange organ composed of an arterial and a venous capillary system that can be catheterized and perfused. Substances are introduced at the arterial input by a constant infusion, and their steady-state concentrations are measured at the arterial and venous outputs. The capillary leakage of four MR contrast agents--Gd-DOTA(MW = 561 D), carboxymethyldextran-Gd-DTPA (MW = 38,900 D), albumin-Gd-DTPA (MW = 92,000 D), AMI-227 (400,000 D<MW<900,000 D)--was characterized by reference to radioactive tracers (3HHO, 22Na, 14C-sucrose, 125I-albumin) by two parameters. These parameters were the concentration ratio of the venous output over the arterial input [C(VOUT)(%)] and the permeability coefficient (P). The transcapillary pathway mechanisms for carboxymethyldextran-Gd-DTPA and albumin-Gd-DTPA were studied by electron microscopy. P values for Gd-DOTA (9.4+/-3.6 x 10(-7) cm/s) and albumin-Gd-DTPA (11.8+/-5.5 x 10(-7) cm/s) were close to P values for 14C-sucrose, while P values for carboxymethyldextran-Gd-DTPA (6.4+/-4.9 x 10(-7) cm/sec) were similar to P values for 125I-albumin. The lowest permeability was observed with AMI-227 (2.7+/-2 x 10(-7) cm/sec). Vesicular transport was demonstrated for carboxymethyldextran-Gd-DTPA and albumin-Gd-DTPA. The transcapillary passage of several MR contrast agents can be characterized with the rete mirabile model. Molecular weight is the major factor influencing transport.