Clinical late phase II trials of MultiHance® (Gd-BOPTA) for the magnetic resonance imaging of liver tumors in Japan

Objective: The purpose of the study was to evaluate the safety and efficacy of Gd-BOPTA for liver imaging and to determine the most appropriate clinical dose to administer. Methods: Gd-BOPTA was administered at a dose of 0.05 (group A), 0.1 (group B), or 0.2 (group C) mmol/kg to 201 patients suspected of having malignant liver tumors who had been referred for magnetic resonance imaging. Dynamic phase images (T1-weighted gradient echo sequences obtained during breath-hold), images obtained within 10 min of Gd-BOPTA injection (spin echo images) and delayed images obtained at 40-120 min after Gd-BOPTA injection (T1-weighted spin echo and gradient echo sequences during breath-hold) were acquired. All post-contrast images were compared with pre- contrast images (T1-and T2-weighted sequences) obtained immediately prior to Gd-BOPTA administration. Safety was assessed in terms of the incidence of adverse events. Results: The contrast efficacy for the dynamic study was classified as (+++) in 39.7% (27/68), 55.4% (36/65), and 47.0% (31/66) for groups A, B, and C, respectively. The contrast efficacy within 10 min of the injection was classified as (+++) in 7.6% (5/66), 16.9% (11/65), and 12.5% (8/64) for groups A, B, and C, respectively. The contrast efficacy at 40-120 min post-injection was classified as (+++) in 4.4% (3/68), 21.5% (14/65), and 20.0% (13/65) for groups A, B, and C, respectively with significant differences noted between groups A and B and groups A and C. As regards safety, the overall incidence of adverse reactions was 3.5% (7/199). Conclusion: Gd-BOPTA is a safe and efficacious contrast agent for use in both dynamic phase imaging and delayed (40-120 min) static imaging. A dose of 0.1 mmol/kg Gd-BOPTA appears to be the ideal dose for use in liver imaging in Japan.