Effects of Gd-DTPA after Osmotic BBB Disruption in a Rodent Model

Abstract

This experiment was done to evaluate the gross neurotoxicity of intravenous Gd-DTPA administered in conjunction with osmotic blood-brain barrier (BBB) disruption and to image a human small cell lung carcinoma intracerebral tumor xenograft before and after osmotic BBB disruption. Neurotoxicity studies were performed in normal Sprague-Dawley rats following osmotic BBB disruption by the injection of 25% mannitol in the right internal carotid artery and intravenous administration of Gd-DTPA (n = 10). Animals were observed for major neurologic changes such as seizure or substantial motor defects, and after death neuropathologic examination was performed. Human small cell lung carcinoma cells were implanted intracerebrally in athymic nude rats (n = 4). Gadopentetate dimeglumine was injected intravenously and serial T1-weighted images were obtained. Blood-brain barrier disruption was produced in each animal, followed by a second dose of intravenous Gd-DTPA, and imaging studies were repeated. No gross neurologic toxicity was observed. Tumors showed dense enhancement in a small area, and BBB disruption resulted in marked enhancement in most of the gray matter of the right cerebral hemisphere. Gadopentetate dimeglumine appears to be safe in doses up to 21 mmol/m2 in conjunction with barrier disruption in rats. A human small cell lung carcinoma intracerebral xenograft provides a useful method to study brain tumors.