Evidence against molecular aggregates in concentrated solutions of X-ray contrast media

Abstract

In order to evaluate the possible existence of large molecular aggregates in concentrated solutions of X-ray contrast media used for medical imaging, a comprehensive study of the effect of the contrast medium concentration on the osmolarity, light scattering and molecular diffusion has been performed for the two X-ray contrast media, Omnipaque (iohexol) and Visipaque (iodixanol). The measured change in osmolarity and light scattering with increasing concentration of contrast medium was well explained by solvent–solute and solute–solute interactions. Minima were observed for both the concentration-normalized osmolarity and the inverse of the concentration-normalized Rayleigh ratio, observations which are incompatible with the hypothesis of aggregation at higher concentrations. From the observed minima, dynamic clusters containing at maximum two to three molecules were demonstrated. The apparent molecular diameter measured with dynamic light scattering, was found to be well predicted from the thermodynamic expression of the concentration dependency of the mutual diffusion coefficient. The observed scattering intensity was incompatible with an actual increase in the geometric size of the scatterers (i.e. aggregation) with increasing concentration. Contrary to the conclusions made by other investigators, the results presented clearly demonstrate the absence of `large colloidal-like structures or molecular aggregates' in the X-ray contrast media investigated.