Diffusion-Weighted Magnetic Resonance Imaging Allows Noninvasive In Vivo Monitoring of the Effects of Combretastatin A-4 Phosphate after Repeated Administration

• Main Authors: Harriet C. Thoeny, Frederik De Keyzer, Feng Chen, Vincent Vandecaveye, Erik K. Verbeken, Bisan Ahmed, Xihe Sun, Yicheng Ni, Hilde Bosmans, Robert Hermans, Allan van Oosterom, Guy Marchal, Willy Landuyt
• Format: Article
• Language: English
• Published: Elsevier 2005-08-01
• Series: Neoplasia: An International Journal for Oncology Research
• Subjects: vascular targeting; anticancer therapy; DW-MRI; necrosis; CA4-P
• Online Access: http://www.sciencedirect.com/science/article/pii/S1476558605801101

The noninvasive assessment of anticancer treatment efficacy is very important for the improvement of therapeutic window. The purpose of the present study was to evaluate the antitumoral effects of the vascular targeting agent, combretastatin A-4 phosphate (CA-4-P), at selected time points after repeated intraperitoneal drug administrations (25 mg/kg), using diffusion-weighted magnetic resonance imaging (DWMRI). The experiments were performed during an overall follow-up period of 3 weeks on WAG/Rij rats with subcutaneously growing rhabdomyosarcomas. Each animal served as its own baseline. The DW-MRI studies were quantified by calculating the apparent diffusion coefficient (ADC) for different low, high b-values to separate the effects on tumor vasculature, cellular integrity. The changes in ADC as well as the extent of necrosis development (proportional to the tumor volume), measured on the MR images, were of comparable magnitude after each treatment. All ADC values showed a significant decrease at 6 hours, followed by a significant increase at 2 days for various CA-4-P administrations. DW-MRI allowed us to monitor both reduction in perfusion, changes in the extent of tumor necrosis after CA-4-P injection. Repeated CA-4-P administration retains efficacy in rat rhabdomyosarcomas, with similar findings after each drug administration.