title: Characterization of tumor angiogenesis with dynamic contrast-enhanced MRI and biodegradable macromolecular contrast agents in mice.
abstract: The efficacy of polydisulfide-based biodegradable macromolecular contrast agents for characterizing tumor angiogenesis was investigated in a mouse model using dynamic contrast-enhanced MRI (DCE-MRI). Biodegradable macromolecular MRI contrast agents, gadopentetate dimeglumine (Gd-DTPA) cystamine copolymers (GDCC), and Gd-DTPA cystine copolymers (GDCP), with molecular weights of 20 and 70 kDa were used in the study. Gadodiamide (Gd [DTPA-BMA]) and albumin labeled with Gd-DTPA [albumin-(Gd-DTPA)] were used as the controls. The DCE-MRI studies were performed in nude mice bearing prostate tumor xenografts from the MDA-PCa-2b cell line. Tumor angiogenic kinetic parameters, including endothelial transfer coefficient (K(PS)), fractional tumor plasma volume (f(PV)), and permeability surface area product (PS), were estimated from the DCE-MRI data using a two-compartment model. The K(PS) and f(PV) values estimated by the biodegradable macromolecular contrast agents were between those estimated by Gd(DTPA-BMA) and albumin-(Gd-DTPA). The parameters estimated by the agent with a slow degradation rate and high molecular weight, GDCP-70 (K(PS) = 2.09 +/- 0.50 ml/min/100 cc and f(PV) = 0.075 +/- 0.021), were closer to those by albumin-(Gd-DTPA) (K(PS) = 1.43 +/- 0.64 ml/min/100 cc and f(PV) = 0.044 +/- 0.007) than by other agents with relatively low molecular weight or rapid degradation rate. The polydisulfide-based biodegradable macromolecular contrast agents are promising for characterizing tumor vascularity and angiogenesis with DCE-MRI.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Feng
authors.forename: Eun-Kee
authors.initials: EK
authors.lastname: Jeong
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Mohs
authors.forename: Lyska
authors.initials: L
authors.lastname: Emerson
authors.forename: Zheng-Rong
authors.initials: ZR
authors.lastname: Lu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media; D004343:Drug Implants / Q000493:pharmacokinetics; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D007089:Image Enhancement / Q000379:methods*; D046911:Macromolecular Substances / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D003287:Contrast Media; D004343:Drug Implants; D046911:Macromolecular Substances; D019786:Gadolinium DTPA