A physiologic imaging pilot study of breast cancer treated with AZD2171

Kathy Miller, Michael Miller, Sanjana Mehrotra, Beamon Agarwal, Bruce H. Mock, Qi-Huang Zheng, Sunil Badve, Gary Hutchins, George W. Sledge

Research output: Contribution to journalArticle

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Abstract

Background: This pilot study combined physiologic imaging, microcomputed tomography, and histologic tumor evaluation with a xenograft model of breast cancer to identify surrogates likely to correlate with response to AZD2171, an inhibitor of the vascular endothelial growth factor (VEGF) receptor tyrosine kinases. Experimental Design: MCF-7 cells transfected with vector (MCF-7 neo) or VEGF (MCFVEGF) were implanted in the right and left mammary fat pads of 75 athymic mice. Treatment with AZD2171 (5 mg/kg/d) or vehicle control was initiated once tumors were established. Positron emission tomography with [11C] carbon monoxide to measure blood volume, [ 18F]fluoromethane to measure perfusion, and [18F] fluorodeoxyglucose to measure glucose utilization was done at baseline, and after 24 hours, 72 hours, and 4 weeks of treatment. After imaging, tumors were analyzed for microvessel density, proliferation, and VEGF expression. Results: AZD2171 induced significant inhibition of tumor growth in established MCF-7 neo xenografts and regression of established MCF-7VEGF xenografts. An acute decrease in blood flow was detected in MCF-7VEGF tumors at 24 hours (P = 0.05). Tumor blood volume was increased in the MCF-7VEGF tumors but correlated with tumor size; blood volume did not change with AZD2171 therapy. Glucose utilization correlated with tumor size and did not change with acute or chronic AZD2171 therapy. Unlike blood flow and blood volume, glucose utilization was similar in MCF-7neo and MCF-7VEGF tumors. Microvessel density and proliferation acutely decreased in MCF-7VEGF tumors but returned to baseline during chronic therapy. Conclusions: [18F] Fluoromethane imaging may be a useful surrogate for biological activity of AZD2171 with changes identified within 24 hours of starting therapy.

Original languageEnglish
Pages (from-to)281-288
Number of pages8
JournalClinical Cancer Research
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2006

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Breast Neoplasms
Neoplasms
Blood Volume
Heterografts
Microvessels
Vascular Endothelial Growth Factor A
cediranib
Glucose
X-Ray Microtomography
Vascular Endothelial Growth Factor Receptor
MCF-7 Cells
Fluorodeoxyglucose F18
Therapeutics
Carbon Monoxide
Tumor Burden
Nude Mice
Positron-Emission Tomography
Protein-Tyrosine Kinases
Blood Glucose
Adipose Tissue

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A physiologic imaging pilot study of breast cancer treated with AZD2171. / Miller, Kathy; Miller, Michael; Mehrotra, Sanjana; Agarwal, Beamon; Mock, Bruce H.; Zheng, Qi-Huang; Badve, Sunil; Hutchins, Gary; Sledge, George W.

In: Clinical Cancer Research, Vol. 12, No. 1, 01.01.2006, p. 281-288.

Research output: Contribution to journalArticle

Miller, Kathy ; Miller, Michael ; Mehrotra, Sanjana ; Agarwal, Beamon ; Mock, Bruce H. ; Zheng, Qi-Huang ; Badve, Sunil ; Hutchins, Gary ; Sledge, George W. / A physiologic imaging pilot study of breast cancer treated with AZD2171. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 1. pp. 281-288.
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abstract = "Background: This pilot study combined physiologic imaging, microcomputed tomography, and histologic tumor evaluation with a xenograft model of breast cancer to identify surrogates likely to correlate with response to AZD2171, an inhibitor of the vascular endothelial growth factor (VEGF) receptor tyrosine kinases. Experimental Design: MCF-7 cells transfected with vector (MCF-7 neo) or VEGF (MCFVEGF) were implanted in the right and left mammary fat pads of 75 athymic mice. Treatment with AZD2171 (5 mg/kg/d) or vehicle control was initiated once tumors were established. Positron emission tomography with [11C] carbon monoxide to measure blood volume, [ 18F]fluoromethane to measure perfusion, and [18F] fluorodeoxyglucose to measure glucose utilization was done at baseline, and after 24 hours, 72 hours, and 4 weeks of treatment. After imaging, tumors were analyzed for microvessel density, proliferation, and VEGF expression. Results: AZD2171 induced significant inhibition of tumor growth in established MCF-7 neo xenografts and regression of established MCF-7VEGF xenografts. An acute decrease in blood flow was detected in MCF-7VEGF tumors at 24 hours (P = 0.05). Tumor blood volume was increased in the MCF-7VEGF tumors but correlated with tumor size; blood volume did not change with AZD2171 therapy. Glucose utilization correlated with tumor size and did not change with acute or chronic AZD2171 therapy. Unlike blood flow and blood volume, glucose utilization was similar in MCF-7neo and MCF-7VEGF tumors. Microvessel density and proliferation acutely decreased in MCF-7VEGF tumors but returned to baseline during chronic therapy. Conclusions: [18F] Fluoromethane imaging may be a useful surrogate for biological activity of AZD2171 with changes identified within 24 hours of starting therapy.",
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AU - Miller, Michael

AU - Mehrotra, Sanjana

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AU - Badve, Sunil

AU - Hutchins, Gary

AU - Sledge, George W.

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AB - Background: This pilot study combined physiologic imaging, microcomputed tomography, and histologic tumor evaluation with a xenograft model of breast cancer to identify surrogates likely to correlate with response to AZD2171, an inhibitor of the vascular endothelial growth factor (VEGF) receptor tyrosine kinases. Experimental Design: MCF-7 cells transfected with vector (MCF-7 neo) or VEGF (MCFVEGF) were implanted in the right and left mammary fat pads of 75 athymic mice. Treatment with AZD2171 (5 mg/kg/d) or vehicle control was initiated once tumors were established. Positron emission tomography with [11C] carbon monoxide to measure blood volume, [ 18F]fluoromethane to measure perfusion, and [18F] fluorodeoxyglucose to measure glucose utilization was done at baseline, and after 24 hours, 72 hours, and 4 weeks of treatment. After imaging, tumors were analyzed for microvessel density, proliferation, and VEGF expression. Results: AZD2171 induced significant inhibition of tumor growth in established MCF-7 neo xenografts and regression of established MCF-7VEGF xenografts. An acute decrease in blood flow was detected in MCF-7VEGF tumors at 24 hours (P = 0.05). Tumor blood volume was increased in the MCF-7VEGF tumors but correlated with tumor size; blood volume did not change with AZD2171 therapy. Glucose utilization correlated with tumor size and did not change with acute or chronic AZD2171 therapy. Unlike blood flow and blood volume, glucose utilization was similar in MCF-7neo and MCF-7VEGF tumors. Microvessel density and proliferation acutely decreased in MCF-7VEGF tumors but returned to baseline during chronic therapy. Conclusions: [18F] Fluoromethane imaging may be a useful surrogate for biological activity of AZD2171 with changes identified within 24 hours of starting therapy.

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