Abstract
Although polymeric magnetic resonance imaging (MRI) agents have significantly improved relaxivity and prolonged circulation time in vivo compared with current imaging agents, the potential for long-term toxicity prevents their translation into the clinic. The aim of this study was to develop a new biodegradable, nonionic polymeric blood pool MRI contrast agent with efficient clearance from the body. We synthesized PHPG-DTPA, which possesses two potentially degradable sites in vivo: protein amide bonds of the polymer backbone susceptible to enzymatic degradation and hydrolytically labile ester bonds in the side chains. After chelation with Gd 3+, PHPG-DTPA-Gd displayed an R 1 relaxivity of 15.72 mm -1{dot operator}sec -1 (3.7 times higher than that of Magnevist T). In vitro, DTPA was completely released from PHPG polymer within 48 h when incubated in mouse plasma. In vivo, PHPG-DTPA-Gd was cleared via renal route as shown by micro-single photon emission computed tomography of mice after intravenous injection of 111In-labeled PHPG-DTPA-Gd. MRI of nude rats bearing C6 glioblastoma showed significant enhancement of the tumor periphery after intravenous injection of PHPG-DTPA-Gd. Furthermore, mouse brain angiography was clearly delineated up to 2 h after injection of PHPG-DTPA-Gd. PHPG-DTPA-Gd's biodegradability, efficient clearance, and significantly increased relaxivity make it a promising polymeric blood pool MRI contrast agent.
Original language | English (US) |
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Pages (from-to) | 5376-5383 |
Number of pages | 8 |
Journal | Biomaterials |
Volume | 33 |
Issue number | 21 |
DOIs | |
State | Published - Jul 2012 |
Keywords
- Biodegradable
- Blood pool imaging
- Magnetic resonance imaging
- Polymeric gadolinium chelates
ASJC Scopus subject areas
- Biomaterials
- Bioengineering
- Ceramics and Composites
- Mechanics of Materials
- Biophysics