PHASE-III MULTICENTER TRIAL OF HIGH-DOSE GADOTERIDOL IN MR EVALUATIONOF BRAIN METASTASES

PURPOSE: To assess the efficacy and safety profile of high-dose (0.3 m mol/kg cumulative dose) gadoteridol in patients with suspected central nervous system metastatic disease. METHODS: We studied 67 patients us ing an incremental-dose technique. Patient monitoring included a medic al history, physical examination, vital signs, and extensive laborator y tests within 24 hours before and after the MR examination. Precontra st T1- and T2-weighted spin-echo studies were performed, followed by i ntravenous injection of 0.1 mmol/kg of gadoteridol. T1-weighted images were acquired immediately after and at 10 and 20 minutes after inject ion. At 30 minutes an additional 0.2 mmol/kg of gadoteridol was admini stered (0.3-mmol/kg cumulative dose), and T1-weighted images were acqu ired. Cases demonstrating abnormal MR findings were assessed for effic acy by unblinded and blinded reviewers and were analyzed quantitativel y. RESULTS: Three adverse effects in two patients were considered to b e related to gadoteridol administration. No adverse effects were serio us; all self-resolved. Forty-nine cases showed abnormal MR findings an d were included in the efficacy analysis. A significantly greater numb er of lesions was seen on the high-dose as opposed to the standard-dos e images. Blinded and unblinded readers identified 5 and 8 patients, r espectively, with solitary lesions on standard-dose examination and mu ltiple lesions on high-dose examination. Two patients who had normal s tandard-dose findings had lesions identified on high-dose studies. Qua ntitative analysis of 133 lesions in 45 patients demonstrated signific ant increases in lesion signal intensity on high-dose studies when com pared with standard-dose studies. CONCLUSION: Gadoteridol can be safel y administered up to a cumulative dose of 0.3 mmol/kg. High-dose contr ast studies provide improved lesion detectability and additional diagn ostic information over studies performed in the same patients with a 0 .1-mmol/kg dose and aid in patient diagnosis and treatment. High-dose gadoteridol study may facilitate the care of patients with suspected c entral nervous system metastasis.