Tumor physiologic response to combretastatin A4 phosphate assessed by MRI

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

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Purpose: To evaluate the effect of the vascular targeting agent, combretastatin A4 phosphate, on tumor oxygenation compared with vascular perfusion/permeability. Methods and Materials: 19F MRI oximetry and dynamic contrast-enhanced (DCE)-MRI were used to monitor tumor oxygenation and perfusion/permeability in syngeneic 13762NF rat breast carcinoma. Results: A significant drop was found in the mean tumor pO2 (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 pO2 in the central and peripheral regions were parallel, but by 24 h after treatment, a significant difference was apparent: the pO2 in the periphery had improved significantly, and the center remained hypoxic. These data are consistent with DCE-MRI, which revealed an ∼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. Conclusion: The response observed by DCE-MRI, indicating vascular shutdown, paralleled the pO2 measurements as expected, but quantitative pO2 measurements are potentially important for optimizing the therapeutic combination of vascular targeting agents with radiotherapy.

Original languageEnglish (US)
Pages (from-to)872-880
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume62
Issue number3
DOIs
StatePublished - Jul 1 2005

Fingerprint

phosphates
tumors
Blood Vessels
permeability
Perfusion
oxygenation
Permeability
Neoplasms
oximetry
shutdowns
Oximetry
Capillary Permeability
curves
breast
rats
radiation therapy
Radiotherapy
Therapeutics
cancer
Breast Neoplasms

Keywords

  • Breast tumor
  • MRI
  • Oxygenation
  • Vascular targeting agent
  • Vasculature

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Tumor physiologic response to combretastatin A4 phosphate assessed by MRI. / Zhao, Dawen; Jiang, Lan; Hahn, Eric W.; Mason, Ralph P.

In: International Journal of Radiation Oncology Biology Physics, Vol. 62, No. 3, 01.07.2005, p. 872-880.

Research output: Contribution to journalArticle

@article{8630e0c996fd4e85a704c814fcc0a856,
title = "Tumor physiologic response to combretastatin A4 phosphate assessed by MRI",
abstract = "Purpose: To evaluate the effect of the vascular targeting agent, combretastatin A4 phosphate, on tumor oxygenation compared with vascular perfusion/permeability. Methods and Materials: 19F MRI oximetry and dynamic contrast-enhanced (DCE)-MRI were used to monitor tumor oxygenation and perfusion/permeability in syngeneic 13762NF rat breast carcinoma. Results: A significant drop was found in the mean tumor pO2 (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 pO2 in the central and peripheral regions were parallel, but by 24 h after treatment, a significant difference was apparent: the pO2 in the periphery had improved significantly, and the center remained hypoxic. These data are consistent with DCE-MRI, which revealed an ∼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. Conclusion: The response observed by DCE-MRI, indicating vascular shutdown, paralleled the pO2 measurements as expected, but quantitative pO2 measurements are potentially important for optimizing the therapeutic combination of vascular targeting agents with radiotherapy.",
keywords = "Breast tumor, MRI, Oxygenation, Vascular targeting agent, Vasculature",
author = "Dawen Zhao and Lan Jiang and Hahn, {Eric W.} and Mason, {Ralph P.}",
year = "2005",
month = "7",
day = "1",
doi = "10.1016/j.ijrobp.2005.03.009",
language = "English (US)",
volume = "62",
pages = "872--880",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Tumor physiologic response to combretastatin A4 phosphate assessed by MRI

AU - Zhao, Dawen

AU - Jiang, Lan

AU - Hahn, Eric W.

AU - Mason, Ralph P.

PY - 2005/7/1

Y1 - 2005/7/1

N2 - Purpose: To evaluate the effect of the vascular targeting agent, combretastatin A4 phosphate, on tumor oxygenation compared with vascular perfusion/permeability. Methods and Materials: 19F MRI oximetry and dynamic contrast-enhanced (DCE)-MRI were used to monitor tumor oxygenation and perfusion/permeability in syngeneic 13762NF rat breast carcinoma. Results: A significant drop was found in the mean tumor pO2 (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 pO2 in the central and peripheral regions were parallel, but by 24 h after treatment, a significant difference was apparent: the pO2 in the periphery had improved significantly, and the center remained hypoxic. These data are consistent with DCE-MRI, which revealed an ∼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. Conclusion: The response observed by DCE-MRI, indicating vascular shutdown, paralleled the pO2 measurements as expected, but quantitative pO2 measurements are potentially important for optimizing the therapeutic combination of vascular targeting agents with radiotherapy.

AB - Purpose: To evaluate the effect of the vascular targeting agent, combretastatin A4 phosphate, on tumor oxygenation compared with vascular perfusion/permeability. Methods and Materials: 19F MRI oximetry and dynamic contrast-enhanced (DCE)-MRI were used to monitor tumor oxygenation and perfusion/permeability in syngeneic 13762NF rat breast carcinoma. Results: A significant drop was found in the mean tumor pO2 (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 pO2 in the central and peripheral regions were parallel, but by 24 h after treatment, a significant difference was apparent: the pO2 in the periphery had improved significantly, and the center remained hypoxic. These data are consistent with DCE-MRI, which revealed an ∼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. Conclusion: The response observed by DCE-MRI, indicating vascular shutdown, paralleled the pO2 measurements as expected, but quantitative pO2 measurements are potentially important for optimizing the therapeutic combination of vascular targeting agents with radiotherapy.

KW - Breast tumor

KW - MRI

KW - Oxygenation

KW - Vascular targeting agent

KW - Vasculature

UR - http://www.scopus.com/inward/record.url?scp=20344378675&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20344378675&partnerID=8YFLogxK

U2 - 10.1016/j.ijrobp.2005.03.009

DO - 10.1016/j.ijrobp.2005.03.009

M3 - Article

C2 - 15936572

AN - SCOPUS:20344378675

VL - 62

SP - 872

EP - 880

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

IS - 3

ER -