TIME-COURSE OF STOMACH MINERALIZATION, PLASMA, AND URINARY CHANGES AFTER A SINGLE INTRAVENOUS ADMINISTRATION OF GADOLINIUM(III) CHLORIDE INTHE MALE-RAT

In a previous experiment it was reported that the intravenous administ ration of gadolinium chloride (GdCl3) to rats results in a discrete ba nd of interstitial mineralization in the fundic glandular mucosa of th e stomach. To investigate the time course for the development of this lesion and its relationship to plasma calcium and phosphate concentrat ions, 2 experiments were carried out in male Sprague-Dawley rats given a single intravenous dose of 0.07 mmol/kg GdCl3. Plasma calcium and p hosphate concentrations approximately doubled between 30 min and 12 hr postdose but had regressed back to near normal values by 24 hr. Howev er, there were no observable clinical signs in treated animals. Histol ogically, there was progressive mineralization of the lamina propria o f the neck region of the fundic glands from 6 hr postdose, forming a d istinctive mineral band by 12 hr postdose. At 7 and 14 days postdose t he mineral deposits were accompanied by mucous cell hyperplasia, inter stitial fibrosis, and a very sparse infiltration of inflammatory cells . By 56 days postdose only occasional mineral deposits remained. Trans mission electron microscopy showed mineral first nucleated on collagen in the interstitium, but there was no evidence of cell necrosis. X-ra y microanalysis showed that the interstitial mineral was composed of c alcium and phosphate in the form of hydroxyapatite; gadolinium (Gd) wa s only very rarely identified. These findings are consistent with meta static mineralization. The source, cause, and the exact nature of the excess plasma calcium and phosphate are unknown, and the possible sign ificance of this effect for clinical use of Gd-containing chelates in nuclear magnetic resonance imaging requires further investigation.