MS-325 - ALBUMIN-TARGETED CONTRAST AGENT FOR MR-ANGIOGRAPHY

PURPOSE: To evaluate the protein-binding and signal enhancement charac teristics of MS-325, a gadolinium-based magnetic resonance (MR) imagin g blood pool agent that binds to albumin, and compare results with tho se obtained with existing gadolinium- and iron oxide-based agents. MAT ERIALS AND METHODS: Protein binding in human plasma was measured by me ans 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-dimens ional fast imaging with steady-state precession, or FISP) was performe d at 1.0 T in phantoms, which contained varying concentrations of diff erent 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 rela xivity approximately six to 10 times that of gadolinium diethylenetria minepentaacetic acid (DTPA). Images of phantoms containing MS-325 were significantly brighter than those containing existing gadolinium chel ates or iron particles (monocrystalline iron oxide nanoparticle, or MI ON) at equivalent concentrations. Findings of in vivo studies indicate d 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. CONCLUSION: MS-325 is highly protein bound after injection and provides vascular signal enhancement superior to t hat provided with other agents. As the first gadolinium-based blood po ol agent in human trials, MS-325 has the potential to enhance both dyn amic and steady-state MR angiograms.