Treatment of rodent liver tumor with combretastatin a4 phosphate: noninvasive therapeutic evaluation using multiparametric magnetic resonance imaging in correlation with microangiography and histology

• Published in: Investigative radiology Vol. 44; no. 1; p. 44
• Main Authors: Wang, Huaijun, Sun, Xihe, Chen, Feng, De Keyzer, Frederik, Yu, Jie, Landuyt, Willy, Vandecaveye, Vincent, Peeters, Ronald, Bosmans, Hilde, Hermans, Robert, Marchal, Guy, Ni, Yicheng
• Format: Journal Article
• Language: English
• Published: United States 01.01.2009
• Subjects: Algorithms; Angiography - methods; Animals; Antineoplastic Agents, Phytogenic - administration & dosage; Contrast Media; Image Enhancement - methods; Image Interpretation, Computer-Assisted - methods; Liver Neoplasms - diagnosis; Liver Neoplasms - drug therapy; Magnetic Resonance Angiography - methods; Male; Neovascularization, Pathologic - diagnosis; Neovascularization, Pathologic - drug therapy; Rats; Reproducibility of Results; Rhabdomyosarcoma - diagnosis; Rhabdomyosarcoma - drug therapy; Sensitivity and Specificity; Statistics as Topic; Stilbenes - administration & dosage; Treatment Outcome
• ISSN: 1536-0210
• DOI: 10.1097/RLI.0b013e31818e5ace

To document tumoricidal events after intravenous administration of a vascular targeting agent combretastatin A-4-phosphate (CA4P) in rodent liver tumors by using multiparametric magnetic resonance imaging (MRI) in correlation with microangiography and histopathology. Thirty rhabdomyosarcomas of 8 to 14 mm in diameter were obtained 16 days after implantation in liver lobes of 15 rats. Using a 1.5T magnet and a 4-channel wrist coil, T2-weighted imaging (T2WI), pre- and postcontrast T1-weighted imaging (T1WI), diffusion-weighted imaging (DWI), and dynamic susceptibility imaging (DSI) with relative blood volume (rBV) and flow (rBF) maps were acquired at baseline, 1 hour, 6 hours, and 48 hours after iv injection of CA4P at 10 mg/kg and vehicle in 9 treated and 6 control rats, respectively. In vivo data including signal intensity (SI), tumor volume, apparent diffusion coefficient (ADC), rBV, and rBF were correlated with ex vivo microangiographic and histopathologic findings. CA4P-treated tumors (n = 18) grew slower than those (n = 12) of controls (P < 0.05), with vascular shutdown evident on CE-T1WI at 1 hour but more prominent at 6 hours. However, enhanced rim occurred in the periphery 48 hours after treatment, indicating neovascularization. ADC map enabled distinction between necrotic and viable tumors. DSI-derived tumoral rBV and rBF decreased significantly at 1 hour through 6 hours and partly recovered at 48 hours. SI-time curve reflected diverse therapeutic responses between tumor and liver. MRI findings were verified by ex vivo techniques. Clinical MRI allowed monitoring of CA4P-related vascular shutdown, necrosis, and neovascularization of liver tumors in rats. Single dose of CA4P seemed insufficient for tumor eradication because of evident peripheral residue and recurrence.