Tumor physiologic response to combretastatin A4 phosphate assessed by MRI

Zhao, Dawen; Jiang, Lan; Hahn, Eric; Mason, Ralph P.

doi:10.1016/j.ijrobp.2005.03.009

Cited by 63 publications

(61 citation statements)

References 29 publications

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“…Dynamic contrast-enhanced MRI has been applied previously both in animal models and the clinic to many tumor types with respect to Combretastatin administration (24,30,32). The changes observed here ( Figure 4, Table 2) are consistent with previous observations (23,30).…”

Section: Discussionsupporting

confidence: 89%

Antivascular effects of combretastatin A4 phosphate in breast cancer xenograft assessed using dynamic bioluminescence imaging and confirmed by MRI

et al. 2008

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Bioluminescent imaging (BLI) has found significant use in evaluating long-term cancer therapy in small animals. We have now tested the feasibility of using BLI to assess acute effects of the vascular disrupting agent Combretastatin A4 phosphate (CA4P) on luciferase expressing MDA-MB-231 human breast tumor cells growing as xenografts in mice. Following administration of luciferin substrate, there is a rapid increase in light emission reaching a maximum after about six minutes, which gradually decreases over the following 20 min. The kinetics of light emission are highly reproducible, however, following IP administration of CA4P (120 mg/kg), the detected light emission was decreased between 50 and 90 percent and time to maximum was significantly delayed. Twenty-four hours later, there was some recovery of light emission following further administration of luciferin substrate. Comparison with dynamic contrast-enhanced MRI based on the paramagnetic contrast agent Omniscan showed comparable changes in the tumors consistent with the previous literature. Histology also confirmed shutdown of tumor vascular perfusion. We believe this provides an important novel application for BLI, which could have widespread application in screening novel therapeutics expected to cause acute vascular changes in tumors.

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Section: Discussionsupporting

confidence: 89%

Antivascular effects of combretastatin A4 phosphate in breast cancer xenograft assessed using dynamic bioluminescence imaging and confirmed by MRI

et al. 2008

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“…The pattern of changes in the DCE-MRI and DW-MRI parameters were similar to what has been observed previously in other tumor types with this drug (4,(34)(35)(36). One-way ANOVA between the curves of Gd-DTPA uptake measured in the DCE-MRI experiments (Fig.…”

supporting

confidence: 85%

Detection of Tumor Response to a Vascular Disrupting Agent by Hyperpolarized 13C Magnetic Resonance Spectroscopy

Bohndiek

Kettunen

et al. 2010

Molecular Cancer Therapeutics

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Nuclear spin hyperpolarization can dramatically increase the sensitivity of the 13 C magnetic resonance experiment, allowing dynamic measurements of the metabolism of hyperpolarized 13 C-labeled substrates in vivo. Here, we report a preclinical study of the response of lymphoma tumors to the vascular disrupting agent (VDA), combretastatin-A4-phosphate (CA4P), as detected by measuring changes in tumor metabolism of hyperpolarized [1- C]pyruvate and lactate was decreased by 34% within 6 hours of CA4P treatment and remained at this lower level at 24 hours. The rate constant describing production of labeled malate from hyperpolarized [1,[4][5][6][7][8][9][10][11][12][13] C 2 ]fumarate increased 1.6-fold and 2.5-fold at 6 and 24 hours after treatment, respectively, and correlated with the degree of necrosis detected in histologic sections. Although DCE-MRI measurements showed a substantial reduction in perfusion at 6 hours after treatment, which had recovered by 24 hours, DW-MRI showed no change in the apparent diffusion coefficient of tumor water at 6 hours after treatment, although there was a 32% increase at 24 hours (P < 0.02) when regions of extensive necrosis were observed by histology. Measurements of hyperpolarized [1- C 2 ]fumarate metabolism may provide, therefore, a more sustained and sensitive indicator of response to a VDA than DCE-MRI or DW-MRI, respectively. Mol Cancer Ther; 9(12); 3278-88. Ó2010 AACR.

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“…Most solid animal and human tumors contain varying degrees of hypoxia (6,117). Following treatment with VDAs, tumor oxygenation status decreases even further (78,(118)(119)(120)(121)(122). This is clearly associated with the increased necrosis, but studies using 19 F magnetic resonance imaging oximetry suggest that there is a decrease in oxygenation status even in viable tissue (122).…”

Section: Pathophysiologic Effects Of Vtasmentioning

confidence: 99%

Pathophysiologic Effects of Vascular-Targeting Agents and the Implications for Combination with Conventional Therapies

2006

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A functional vascular supply is critical for the continued growth and development of solid tumors. It also plays a major role in metastatic spread of tumor cells. This importance has led to the concept of targeting the vasculature of the tumor as a form of cancer therapy. Two major types of vasculartargeting agent (VTA) have now emerged: those that prevent the angiogenic development of the neovasculature of the tumor and those that specifically damage the already established tumor vascular supply. When used alone neither approach readily leads to tumor control, and so, for VTAs to be most successful in the clinic they will need to be combined with more conventional therapies. However, by affecting the tumor vascular supply, these VTAs should induce pathophysiologic changes in variables, such as blood flow, pH, and oxygenation. Such changes could have negative or positive influences on the tumor response to more conventional therapies. This review aims to discuss the pathophysiologic changes induced by VTAs and the implications of these effects on the potential use of VTAs in combined modality therapy.

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Tumor physiologic response to combretastatin A4 phosphate assessed by MRI

Cited by 63 publications

References 29 publications

Antivascular effects of combretastatin A4 phosphate in breast cancer xenograft assessed using dynamic bioluminescence imaging and confirmed by MRI

Antivascular effects of combretastatin A4 phosphate in breast cancer xenograft assessed using dynamic bioluminescence imaging and confirmed by MRI

Detection of Tumor Response to a Vascular Disrupting Agent by Hyperpolarized 13C Magnetic Resonance Spectroscopy

Pathophysiologic Effects of Vascular-Targeting Agents and the Implications for Combination with Conventional Therapies

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