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OBJECTIVE To evaluate the protein-binding and signal enhancement characteristics of MS-325, a gadolinium-based magnetic resonance (MR) imaging blood pool agent that binds to albumin, and compare results with those obtained with existing gadolinium- and iron oxide-based agents. METHODS Protein binding in human plasma was measured by means of ultrafiltration. T1 relaxation times (20 MHz) were measured in human plasma or ex vivo samples from rabbits and monkeys injected with 0.1 mmol of MS-325 per kilogram of body weight. Imaging (three-dimensional fast imaging with steady-state precession, or FISP) was performed at 1.0 T in phantoms, which contained varying concentrations of different agents, or rabbits after injection of 0.015-0.100 mmol/kg MS-325. RESULTS MS-325 is 80%-96% bound in human plasma and exhibits a relaxivity approximately six to 10 times that of gadolinium diethylenetriaminepentaacetic acid (DTPA). Images of phantoms containing MS-325 were significantly brighter than those containing existing gadolinium chelates or iron particles (monocrystalline iron oxide nanoparticle, or MION) at equivalent concentrations. Findings of in vivo studies indicated strong, persistent plasma T1 reduction with MS-325 for 1 hour (T1 of MS-325, 50-100 msec; T1 of Gd-DTPA, 200-400 msec) and strong vascular enhancement on MR images. CONCLUSIONS MS-325 is highly protein bound after injection and provides vascular signal enhancement superior to that provided with other agents. As the first gadolinium-based blood pool agent in human trials, MS-325 has the potential to enhance both dynamic and steady-state MR angiograms.
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