title: The degradation and clearance of Poly(N-hydroxypropyl-L-glutamine)-DTPA-Gd as a blood pool MRI contrast agent.
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)⋅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 (111)In-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.
authors.affiliation: Department of Experimental Diagnostic Imaging, Box 59, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Guodong
authors.initials: G
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Marites P
authors.initials: MP
authors.lastname: Melancon
authors.forename: Kelvin
authors.initials: K
authors.lastname: Wong
authors.forename: Jian
authors.initials: J
authors.lastname: You
authors.forename: Qian
authors.initials: Q
authors.lastname: Huang
authors.forename: James
authors.initials: J
authors.lastname: Bankson
authors.forename: Dong
authors.initials: D
authors.lastname: Liang
authors.forename: Chun
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging; D002855:Chromatography, Thin Layer; D003287:Contrast Media / Q000493:pharmacokinetics*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D019786:Gadolinium DTPA / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics* / Q000031:analogs & derivatives; D015637:Gated Blood-Pool Imaging / Q000379:methods*; D007205:Indium Radioisotopes; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides; D011506:Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: D003287:Contrast Media; D056831:Coordination Complexes; D007205:Indium Radioisotopes; D010455:Peptides; D011506:Proteins; C574941:poly(N-hydroxypropylglutamine)-DTPA-Gd; D019786:Gadolinium DTPA