An extracellular MRI polymeric contrast agent that degrades at physiological pH.
Macromolecular contrast agents have the potential to assist magnetic resonance imaging (MRI) due to their high relaxivity, but are not clinically useful because of toxicity due to poor clearance. We have prepared a biodegradable ketal-based polymer contrast agent which is designed to degrade rapidly at physiological pH by hydrolysis, facilitating renal clearance. In vitro, the agent degraded more rapidly at lower pH, with complete fragmentation after 24 h at pH 7.4. In vitro relaxivity measurements showed a direct correlation between molecular weight and relaxivity. We compared our polymer contrast agent with commercially available Magnevist in vivo by MRI imaging, as well as measuring the Gd concentration in blood. Our results show that our polymer contrast agent gives a higher contrast and intensity in the same organs and areas as Magnevist and is cleared from the blood at a similar rate. We aim to improve our polymer contrast agent design to develop it for use as a MRI contrast agent, and explore its use as a platform for other imaging modalities.
Skaggs School of Pharmacy and Pharmaceutical Sciences, ⊥Department of NanoEngineering, §Department of Chemistry, and ∥Department of Radiology, University of California at San Diego , La Jolla, California 92093, United States.
Eric
E
Schopf
Jagadis
J
Sankaranarayanan
Minnie
M
Chan
Robert
R
Mattrey
Adah
A
Almutairi
D000818:Animals; D003287:Contrast Media / Q000737:chemistry*; D005260:Female; D005682:Gadolinium / Q000097:blood / Q000737:chemistry; D019786:Gadolinium DTPA / Q000097:blood / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008970:Molecular Weight; D011108:Polymers / Q000737:chemistry*
D003287:Contrast Media; D011108:Polymers; D005682:Gadolinium; D019786:Gadolinium DTPA