Neo-adjuvant (pre-surgical) chemotherapy followed by mastectomy or lumpectomy and axillary node dissection has been successful in treating women with locally advanced breast cancer without distant metastases. Currently, decisions on how long to treat prior to surgery are hampered by the inability to accurately assess tumor response to therapy and the extent of residual viable tumor following treatment. In our preliminary patient studies, the Nuclear Medicine tracers [F-18]-fluorodeoxyglucose (FDG) and [Tc-99m]-Sestamibi (MIBI) have shown promise as accurate markers of tumor response. FDG is a PET tracer whose uptake reflects glucose metabolism, and it has been studied as a tracer of tumor response and viability for a variety of tumors, including preliminary investigations in breast cancer. MIBI is a more readily available single-photon tracer whose uptake most likely reflects a combination of tumor blood flow and metabolism. Our preliminary evaluation of MIBI to measure response to therapy has been encouraging. Our hypotheses are (1) that FDG or MIBI or both will provide accurate and timely measures of response to chemotherapy and the amount of residual viable tumor after therapy in patients with locally advanced breast cancer undergoing pre- surgical chemotherapy and (2) that the combination of MIBI and FDG together with O-15 water measurements of tumor blood flow will be able to characterize how breast tumors respond as they are treated and may be able to predict the likelihood of further response. We plan to (1) perform a clinical trial to determine the accuracy of FDG and MIBI for measuring response to therapy in comparison to the histopathological analysis of post-therapy surgical specimens and (2) compare relative MIBI and FDG uptake to O-15 water tumor blood flow measurements and immunocytochemistry markers of tumor vascularity and multi-drug resistance, as well as the ultimate degree of response. If successful, this work will result in the ability to perform measurements of tumor response that will significantly improve the treatment of patients with locally advanced breast cancer and will lead to insights into how these tumors respond when treated with neo-adjuvant chemotherapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA072064-03
Application #
2712825
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Menkens, Anne E
Project Start
1996-08-01
Project End
2001-05-31
Budget Start
1998-06-01
Budget End
1999-05-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Washington
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Linden, Hannah M; Peterson, Lanell M; Fowler, Amy M (2018) Clinical Potential of Estrogen and Progesterone Receptor Imaging. PET Clin 13:415-422
Wangerin, Kristen A; Muzi, Mark; Peterson, Lanell M et al. (2017) A virtual clinical trial comparing static versus dynamic PET imaging in measuring response to breast cancer therapy. Phys Med Biol 62:3639-3655
Kurland, Brenda F; Muzi, Mark; Peterson, Lanell M et al. (2016) Multicenter Clinical Trials Using 18F-FDG PET to Measure Early Response to Oncologic Therapy: Effects of Injection-to-Acquisition Time Variability on Required Sample Size. J Nucl Med 57:226-30
Muzi, Mark; Peterson, Lanell M; O'Sullivan, Janet N et al. (2015) 18F-Fluoromisonidazole Quantification of Hypoxia in Human Cancer Patients Using Image-Derived Blood Surrogate Tissue Reference Regions. J Nucl Med 56:1223-8
Wangerin, Kristen A; Muzi, Mark; Peterson, Lanell M et al. (2015) Effect of (18)F-FDG uptake time on lesion detectability in PET imaging of early stage breast cancer. Tomography 1:53-60
Doot, Robert K; Kurland, Brenda F; Kinahan, Paul E et al. (2012) Design considerations for using PET as a response measure in single site and multicenter clinical trials. Acad Radiol 19:184-90
Kurland, Brenda F; Peterson, Lanell M; Lee, Jean H et al. (2011) Between-patient and within-patient (site-to-site) variability in estrogen receptor binding, measured in vivo by 18F-fluoroestradiol PET. J Nucl Med 52:1541-9
Dunnwald, Lisa K; Doot, Robert K; Specht, Jennifer M et al. (2011) PET tumor metabolism in locally advanced breast cancer patients undergoing neoadjuvant chemotherapy: value of static versus kinetic measures of fluorodeoxyglucose uptake. Clin Cancer Res 17:2400-9
Linden, Hannah M; Kurland, Brenda F; Peterson, Lanell M et al. (2011) Fluoroestradiol positron emission tomography reveals differences in pharmacodynamics of aromatase inhibitors, tamoxifen, and fulvestrant in patients with metastatic breast cancer. Clin Cancer Res 17:4799-805
Peterson, Lanell M; Kurland, Brenda F; Link, Jeanne M et al. (2011) Factors influencing the uptake of 18F-fluoroestradiol in patients with estrogen receptor positive breast cancer. Nucl Med Biol 38:969-78

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