This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Miller, K. D. Articles by Sledge, G. W. Search for Related Content PubMed PubMed Citation Articles by Miller, K. D. Articles by Sledge, G. W., Jr.

A Physiologic Imaging Pilot Study of Breast Cancer Treated with AZD2171

Authors' Affiliations: ¹ Division of Hematology and Oncology, Department of Medicine; ² Division of Imaging Sciences, Department of Radiology; and ³ Department of Pathology, Indiana University, Indianapolis, Indiana

Requests for reprints: Kathy D. Miller, Division of Hematology and Oncology, Indiana University, Indiana Cancer Pavilion, 535 Barnhill Drive, RT-473, Indianapolis, IN 46202. Phone: 317-274-0920; Fax: 317-274-3646; E-mail: kathmill{at}iupui.edu.

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 (MCF^VEGF) 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-7^VEGF xenografts. An acute decrease in blood flow was detected in MCF-7^VEGF tumors at 24 hours (P = 0.05). Tumor blood volume was increased in the MCF-7^VEGF 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-7^neo and MCF-7^VEGF tumors. Microvessel density and proliferation acutely decreased in MCF-7^VEGF 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.

This article has been cited by other articles:

				W. A. Weber Positron Emission Tomography As an Imaging Biomarker J. Clin. Oncol., July 10, 2006; 24(20): 3282 - 3292. [Abstract] [Full Text] [PDF]