## Abstract The structures of polydisulfide‐based biodegradable macromolecular Gd(III) complexes were modified to improve their in vivo retention time and MRI contrast enhancement. Steric hindrance was introduced around the disulfide bonds to control their access to free thiols in order to alter th
Characterization of tumor angiogenesis with dynamic contrast-enhanced MRI and biodegradable macromolecular contrast agents in mice
✍ Scribed by Yi Feng; Eun-Kee Jeong; Aaron M. Mohs; Lyska Emerson; Zheng-Rong Lu
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 738 KB
- Volume
- 60
- Category
- Article
- ISSN
- 0740-3194
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✦ Synopsis
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. Magn Reson Med 60:1347–1352, 2008. © 2008 Wiley‐Liss, Inc.
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