Dy-EOB-DTPA: Tolerance and pharmacokinetics in healthy volunteers and preliminary liver imaging in patients

RATIONALE AND OBJECTIVES. To investigate the tolerance and pharmacokinetics of the new liver-specific x-ray contrast agent Dy-EOB-DTPA [(4S)-4-(4-etho xybenzyl)-3,6,9-tris(carboxylatomethyl)-3,6,9-triazaundecanedioic acid, dys prosium (Dy) complex, disodium salt] in healthy volunteers and to obtain pr eliminary imaging data by abdominal spiral computed tomography (CT) in tumo r patients with liver metastases. METHODS. A total of 40 healthy male volunteers received 10-minute intraveno us infusions of 0.05, 0.1, 0.25, 0.375, or 0.5 mmol/kg Dy-EOB-DTPA (n = 6 p er dose group) or placebo (n = 10). Blood, urine, and feces were sampled fo r Dy measurements by inductively coupled plasma atomic emission spectrometr y (ICP-AES) and for the detection of possible metabolites by high-performan ce liquid chromatography analysis with ICP-AES detection. Safety parameters were determined before, during, and after the study. Two patients with sus pected liver metastases first received 120 mL of iopromide (300 mg iodine/m L; approximate to0.6 mmol/kg) and, 24 or 72 hours later, Dy-EOB-DTPA at a d ose of 0.25 mmol/kg. Computed tomography images were obtained 50 seconds af ter iopromide administration and before and 90 minutes after Dy-EOB-DTPA ad ministration. RESULTS. Dysprosium-EOB-DTPA was well tolerated. At the higher doses (0.375 and 0.5 mmol/kg), there was a slight increase in side effect intensity. In general, nausea, headache, and paresthesia mainly were reported as mild to moderate adverse events. Laboratory parameters did not exceed the normal r ange. Electrocardiographic, vital sign, or hemodynamic parameters were not affected by contrast agent administration. The terminal half-life of elimin ation of Dy-EOB-DTPA was approximately 1.5 hours, total clearance was 2 to 3 mL . min(-1) . kg(-1), and the renal clearance was approximately 1.5 mL . min(-1) . kg(-1). There was a significant dose dependence for the followin g parameters: maximal concentration in blood, terminal half-life, mean resi dence time, total clearance, urinary excretion, and fecal excretion. The vo lume of distribution in the steady state and renal clearance were not depen dent on dose. In the blood and urine, no metabolites of Dy-EOB-DTPA could b e detected. In the tumor patients, CT scanning after Dy-EOB-DTPA injection increased the number of detected metastases from 27 (plain scan) to 40 (iop romide) and then to 41 (Dy-EOB-DTPA) in patient No. I and from I (plain sca n and iopromide) to 3 (Dy-EOB-DTPA) in patient No. 2. CONCLUSIONS. Dysprosium-EOB-DTPA was shown to be a well-tolerated liver-spe cific contrast agent. Its pharmacokinetic profile is characterized by a ter minal half-life of approximately 1.5 hours. There are indications of satura tion of liver uptake at the highest dose level of 0.5 mmol/kg. In compariso n with plain scans and scans performed after iodinated contrast agent admin istration, Dy-EOB-DTPA seems to increase the number of detectable liver les ions.