DESCRIPTION (provided by applicant): The prognosis for patients with metastatic hormone refractory prostate cancer (HRPC) is poor with a median survival of 16 to 18 months despite modern chemotherapy. Docetaxel, alone or in combination with other chemotherapeutic agents, is currently the most active treatment available for HRPC. However, because docetaxel confers only a modest survival benefit, there is a need for more effective drugs. Unfortunately, difficulties in imaging and quantifying disease progression in HRPC have continued to hinder drug development and clinical trials. Molecular imaging techniques such as positron emission tomography/ computed tomography (PET/CT) may contribute novel ways of measuring tumor responses to therapy for both clinical trials and clinical practice. Fluorine-18 fluorocholine (18F-choline) is an investigational PET tracer that has shown considerable promise for imaging hormone-refractory and hormone-naive prostate cancer. In pilot studies, docetaxel has been shown to modulate the uptake of 18F-choline by metastatic tumors. Our goal is to determine whether measurement of these treatment-associated changes in tumor 18F-choline uptake can be used to gauge therapeutic response in HRPC. This R21 proposal to study the short-term effects of docetaxel and androgen hormone manipulation on 18F-choline metabolism will resolve methodological issues relevant to the design of a longitudinal study evaluating 18F-choline PET/CT-based measures as surrogate markers for survival and pain outcomes in patients with HRPC receiving chemotherapy. Our aims are: 1) examine the relationship between changes in tumor 18F-choline uptake and changes in prostate specific antigen level in response to docetaxel treatment of HRPC, 2) examine the time course by which changes in tumor 18F-choline uptake occur during docetaxel chemotherapy, and 3) examine the effects of anti-androgen drug withdrawal on tumor 18F-choline uptake in prostate cancer that is becoming hormone-insensitive. The feasibility of a longitudinal study to evaluate 18F-choline PET/CT as a tumor response measure in HRPC will be based on meeting these aims. Pursuit of these aims may also result in a technique to aid in treating and investigating docetaxel and hormone resistance in HRPC.
PUBLIC HEALTH RELEVANCE: Despite modern advancements in chemotherapy, the prognosis for patients with metastatic prostate cancer is poor and virtually all deaths from prostate cancer are due to metastatic disease. Difficulties in imaging and quantifying the disease continue to create barriers for new drug development and clinical trials. We propose to investigate a method of molecular imaging that in concert with conventional imaging could enhance the ability to detect, monitor, and predict the effects of chemotherapy on metastatic tumors, to the point that effective treatments can be customized based on the tumor characteristics of each individual patient.