Distribution of gadomelitol in a human breast tumor model in mice

The study evaluates the tumor distribution of the rapid clearance blood pool agent (RCBPA) gadomelitol, in a breast tumor model. Different techniques were used : (1) tissue gadolinium concentrations measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES), (2) whole body quantitative autoradiography using radiolabeled [153Gd] gadomelitol and (3) dynamic contrast-enhanced MRI with compartmental analysis. An accumulation of gadomelitol in tumors compared to muscle was observed 30 min and 3 h post injection (p.i.). Thirty minutes p.i., the gadomelitol tumor distribution evaluated by autoradiography showed a marked difference between the rim and the center, whereas both areas showed comparable concentrations after 3 h. Using dynamic contrast-enhanced MRI, three phases could be observed during the 1 hour observation period: (1) rapid tumor uptake within the first few minutes post-injection (2) a progressive increase in tumor signal enhancement over 10 min and (3) a steady-state phase. Average +/- SD (n=5) transendothelial permeability K(PS) and the fractional blood volume fBV were 12.2+/-1.6 microl/min(-1)/g and 5.4+/-0.2% respectively. Due to its slow extravasation and high tumor residence time, gadomelitol may potentially be useful to improve characterization between benign versus malignant tumors using dynamic MRI.