COMPARISON OF GADOLINIUM CY(2)DOTA, A NEW HEPATOBILIARY AGENT, AND GADOLINIUM HP-DO3A, AN EXTRACELLULAR AGENT, IN HEALTHY LIVER AND METASTATIC DISEASE

RATIONALE AND OBJECTIVES. A new gadolinium (Gd) chelate with preferential hepatobiliary uptake, Gd Cy(2)DOTA, was compared in two animal species with Gd HP-DO3A (gadoteridol), a clinically approved contrast agent with extracellular distribution. Liver enhancement was evaluated for these two contrast agents using magnetic resonance imaging, whereas an experimental model of metastatic disease was used to evaluate the agents' efficacy for liver-lesion delineation. METHODS. The two agents were compared in four healthy Rhesus monkeys (eight studies) and five New Zealand White rabbits with implanted VX-2 liver tumors (ten studies). The contrast dose was 0.1 mmol/kg, with the agents given in random order and at least 72 hours between contrast injections. Breathhold T1-weighted spin echo scans were obtained at 1.5 tesla (T) before and after contrast was administered. Postcontrast scans were obtained I to 90 minutes after injection in the monkeys and I to 240 minutes after injection in the rabbits. RESULTS. Prolonged hepatic enhancement, superior in degree to that with Gd HP-DO3A, was noted in both monkeys and rabbits after injection of Gd Cy(2)DOTA. Two minutes after contrast, liver SI was 1.94 +/- 0.05 with Gd Cy(2)DOTA compared with 1.51 +/- 0.05 with Gd HP-DO3A in monkeys. Sixty minutes after contrast, liver SI was 1.60 +/- 0.09 compared with 1.20 +/- 0.02. The difference between agents was significant at all times from 2 to 60 minutes after contrast injection (P < 0.01). Excretion of contrast into the gall bladder was observed in both animal species with Gd Cy(2)DOTA but not with Gd HP-DO3A. The maximum improvement in lesion conspicuity (rabbit) occurred 45 minutes after injection of Gd Cy(2)DOTA and 5 minutes after injection of Gd HP-DO3A. Sixty minutes after injection, liver-lesion contrast was 246 +/- 61 with Gd Cy(2)DOTA and 106 +/- 28 with Gd HP-DO3A, with a significant difference (P < 0.02). CONCLUSIONS. Gd Cy(2)DOTA provides greater enhancement of the liver parenchyma on immediate and delayed magnetic resonance scans than does Gd HP-DO3A. On delayed scans, Gd Cy(2)DOTA provides superior delineation of metastatic liver lesions.