Tumor physiologic response to combretastatin A4 phosphate assessed by MRI

Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9058, USA.
International Journal of Radiation OncologyBiologyPhysics (Impact Factor: 4.18). 08/2005; 62(3):872-80. DOI: 10.1016/j.ijrobp.2005.03.009
Source: PubMed

ABSTRACT To evaluate the effect of the vascular targeting agent, combretastatin A4 phosphate, on tumor oxygenation compared with vascular perfusion/permeability.
(19)F MRI oximetry and dynamic contrast-enhanced (DCE)-MRI were used to monitor tumor oxygenation and perfusion/permeability in syngeneic 13762NF rat breast carcinoma.
A significant drop was found in the mean tumor pO(2) (23 to 9 mm Hg, p <0.05) within 90 min after treatment (30 mg/kg of combretastatin A4 phosphate) and a further decrease was observed at 2 h (mean 2 mm Hg; p <0.01). The initial changes in pO(2) in the central and peripheral regions were parallel, but by 24 h after treatment, a significant difference was apparent: the pO(2) in the periphery had improved significantly, and the center remained hypoxic. These data are consistent with DCE-MRI, which revealed an approximately 70% decrease in perfusion/permeability (initial area under signal-intensity curve) at 2 h (p <0.001). The initial area under signal-intensity curve recovered fully after 24 h in a thin peripheral region, but not in the tumor center.
The response observed by DCE-MRI, indicating vascular shutdown, paralleled the pO(2) measurements as expected, but quantitative pO(2) measurements are potentially important for optimizing the therapeutic combination of vascular targeting agents with radiotherapy.

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    • "Furthermore, in order to improve the accuracy of MRI investigators have turned to dynamic contrast enhanced MRI (DCE-MRI), a functional imaging technique that uses low or high molecular weight contrast media and a model-based post processing to provide parameters relating to microvascular characteristics of tissue non-invasively (Engelbrecht et al. 2002, Beyersdorff et al. 2003, Kiessling et al. 2004, Beyersdorff and Hamm 2005, Fü tterer et al. 2005, Kim et al. 2005, Fuchsjäger et al. 2008). Since cancer tissue has been characterised by higher permeability and lower extracellular volume fraction and evidence is mounting that the kinetic parameters derived from DCE T1-w MRI correlate with immuno-histochemical markers of tumour angiogenesis, and consequently may be indicators for tumour microvascular density and microvascular permeability, DCE-MRI should help to differentiate between malignant and benign tissue (Tofts 1997, Tofts et al. 1999, Hara et al. 2005, Zhao et al. 2005). "
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    • "; Eikesdal et al. [22]], which is later than the onset of effects such as hypoxia [23], perfusion [24], and increased vascular resistance [18]. "
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    • "Tozer et al. [26], using intravital microscopy, showed that a complete tumor blood flow shutdown can be obtained within 20 minutes after VDA administration. Zhao et al. [27] found a significant decrease in perfusion/permeability at 2 hours following CA4P administration. In addition, in a recent phase I clinical trial, Anderson et al. [23] showed significant reductions in tumor perfusion, as measured with PET 30 minutes after CA4P administration. "
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