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PET Imaging of Estrogen Metabolism in Breast Cancer

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Annual rept. 1 Jun 2000-31 May 2001

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We propose that estrogen metabolism in breast cancer can be imaged with positron emission tomography PET. It is well known that many breast tumors associate with estrogen and the presence of catecholestrogens in breast tumors cause changes in the DNA which may lead to uncontrolled cell growth. Catecholestrogens are broken down by an enzyme called catechol-O-methyltransferase COMT. COMT is known to be elevated in malignant breast tumors, and abnormal COMT genetics have recently been found in individuals with breast cancer. We have developed 18FRo41-0960, the first radiotracer for visualizing COMT with PET. The hypothesis that 18FRo4l-0960 can map COMT was demonstrated both in vivo and ex vivo in baboon and rodents. We have also adapted our COMT enzyme assay method and performed studies in breast tumor tissue samples from cancer patients undergoing surgery. Preliminary results showed elevated COMT activities in the breast tumor tissues of all patients studied the difference can be as high as 26 fold increase. We then carried out toxicology tests and submifted an IND application that was finally approved by the FDA on Oct., 1999 to conduct studies in breast cancer patients. After receiving the IND, we have been working on documents that required to get approvals from the llSRRB at US Army Medical Research and local IRBs at BNL and Stony Brook. This novel approach to an extremely important medical problem goes beyond diagnosis in that it seeks to delineate the fundamental biochemical properties and molecular signatures of tumor cells. PET imaging studies on breast cancer patients are underway.

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  • Medicine and Medical Research

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