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In vitro setup to study permeability characteristics of contrast agents by MRI.

M. Heilmann, J. Vautier, P. Robert and A. Volk

Contrast Media Mol Imaging, 4 (2), pp.66-72

An experimental setup consisting of a hollow fiber module (HFM) was developed for the in vitro study of contrast agent (CA) permeability. Controllable flow and known fiber characteristics allowed permeability studies under well-defined conditions with CAs of different molecular weight (MW). In the MRI experiments performed at 4.7 T, the system was perfused at a constant flow rate (5 ml/min) with water and four CA of different MW: Gd-DOTA (MW = 0.6 kDa), P846 (3.5 kDa), P792 (6.5 kDa) and P717 (50.5 kDa). R(1) time courses were measured with a saturation-recovery multi-gradient-echo snapshot sequence in the fiber-free HFM input and the fiber-filled center. Concentration time courses were calculated, and CA extravasation was analyzed with a pharmacokinetic model yielding exchange rate constant k(ie). Only Gd-DOTA (k(ie) = 2.37 +/- 0.16 min(-1)) and P846 (k(ie) = 0.58 +/- 0.17 min(-1)) showed quantifiable extravasation. P717 perfusion yielded an intra-capillary volume fraction of 15.6 +/- 2.7\% compared with 12\% estimated from the HFM manufacturer's specifications. In conclusion, the experimental setup allowed classification of in vitro permeability characteristics for CAs with different MW and therefore holds potential for systematic comparison of CAs currently under development. Copyright (c) 2009 John Wiley & Sons, Ltd.