Head-to-Head Comparison of Fibromicellar, Spherical micellar, Polymeric and Small Molecule MRI-Contrast Agents

L.M. Randolph, C.L.M. LeGuyader, M.E. Hahn, C.M. Andolina, R.F. Mattrey, J.E. Millstone, M. Botta, M. Scadeng, N.C. Gianneschi
University of California, San Diego, US

Keywords: polymeric nanoparticles, MRI, gadolinium, intraperitoneal injection

Summary:

A norbornene-based analogue of the FDA approved small molecule MRI contrast agent Gd-DOTA, was synthesized and polymerized via ring-opening metathesis polymerization as a hydrophilic component in water-soluble or amphiphilic block copolymers. The amphiphiles assembled in aqueous solution to form micellar nanoparticles of spherical or fibril-shaped morphology. These two types of particles have water-soluble shells containing a polymerized block of Gd-DOTA, while the analogous hydrophilic polymeric species was completely dispersed in aqueous solution. This study directly compares these materials to each other and to the small molecule Gd-DOTA agent when introduced via intraperitoneal (IP) injection into mice. Clearance to the bladder was observed in anatomical scans via MRI, and through a decrease in T1 over time. Clearance was rapid for Gd-DOTA with minimum T1 times observed in the bladder at 2 hours. Similarly, clearance through the bladder was observable for the dispersed, hydrophilic Gd-labeled polymer. This behavior was in contrast to that observed for nanoparticle formulations, whereby little clearance through the bladder was observed, and considerable retention within the IP space is seen for the first few hours. After one week, clearance was equivalent for all materials as determined by ICP-MS.