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Published on: September 11, 2013
Characterization of tumor angiogenesis with dynamic contrast-enhanced MRI and biodegradable macromolecular contrast
Yi Feng1, Eun-Kee Jeong, Aaron M Mohs
1Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, USA.
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.
Insights
Biodegradable macromolecular contrast agents show promise for characterizing tumor angiogenesis using dynamic contrast-enhanced MRI (DCE-MRI). Agents with slower degradation and higher molecular weight provided more accurate tumor vascularity and angiogenesis parameters.
Area of Science:
- Biomedical Imaging
- Materials Science
- Oncology
Background:
- Tumor angiogenesis characterization is crucial for cancer diagnosis and treatment monitoring.
- Dynamic contrast-enhanced MRI (DCE-MRI) is a valuable tool for assessing tumor vascularity.
- Development of novel contrast agents is essential for improving DCE-MRI efficacy.
Purpose of the Study:
- To investigate the efficacy of polydisulfide-based biodegradable macromolecular contrast agents for characterizing tumor angiogenesis.
- To evaluate the performance of these novel agents in a preclinical mouse model using DCE-MRI.
- To compare the derived angiogenic kinetic parameters with established contrast agents.
Main Methods:
- Synthesis of biodegradable macromolecular MRI contrast agents: gadopentetate dimeglumine (Gd-DTPA) cystamine copolymers (GDCC) and Gd-DTPA cystine copolymers (GDCP) with varying molecular weights (20 and 70 kDa).
- In vivo DCE-MRI studies were conducted on nude mice bearing prostate tumor xenografts (MDA-PCa-2b cell line).
- Tumor angiogenic kinetic parameters (K(PS), f(PV), PS) were estimated using a two-compartment model from DCE-MRI data.
Main Results:
- Biodegradable macromolecular agents yielded K(PS) and f(PV) values intermediate to Gd(DTPA-BMA) and albumin-(Gd-DTPA).
- The GDCP-70 agent (70 kDa, slow degradation) demonstrated results closer to albumin-(Gd-DTPA) for K(PS) and f(PV).
- These findings suggest that molecular weight and degradation rate influence the accuracy of estimated angiogenic parameters.
Conclusions:
- Polydisulfide-based biodegradable macromolecular contrast agents are promising for DCE-MRI.
- These agents show potential for accurate characterization of tumor vascularity and angiogenesis.
- Further research may optimize these agents for enhanced diagnostic capabilities in oncology.
