Clinical progression of prostate cancer is based on key molecular changes in the cancer cell, and this knowledge of tumor biology is now being incorporated into the therapeutic plan for locally aggressive or advanced tumors. In this translational research project our primary goal is to evaluate the role for whole body Positron Emission Tomography (PET) imaging in the diagnosis and therapy of prostate cancer. Our preliminary studies have shown that whole body Positron Emission Tomography (PET) imaging detects abnormal metabolism in a majority of tumor sites in patients pre-selected for progression of prostate cancer. Furthermore, these pilot studies suggest that changes in metabolism during therapy are an early indicator of tumor response. To evaluate a role for PET in diagnosis, we will study pre-surgical patients with prostate cancer and a high likelihood of loco-regional metastases based on well-established clinical nomograms. A comparison will be made to conventional diagnostic imaging methodologies and surgery will be the gold standard. In addition, to assess the role of PET in therapy, we will perform PET studies before and after treatment in patients with progressive prostate cancer, who are undergoing experimental drug therapies directed at rapidly dividing cells or key molecular targets such as androgen receptor and her-2-neu receptor. PET radiotracers will include 18FDOG and 11C-methionine, selected to image changes in glycolysis, and amino acid transport and retention during disease progression and response. A third tracer of androgen receptor expression 18F-fluorodihydrotestosterone (18F-DHT) will be investigated in terms of its pharmacokinetics and biodistribution, as a pilot project. Two major hypotheses will be tested in this project:(1) Metabolic alterations in glycolysis and or amino-acid transport and retention, reflect changes in tumor 1 biology that offer sufficient competitive advantage to the tumor cell that these biochemical changes as measured by PET s will correlate with clinical measures of biologic aggressiveness, including tumor progression, time to PSA recurrence, time to metastasis and survival, in both locally aggressive and metastatic tumors (2) Changes in the uptake of FOG and or methionine from pre and post treatment scans, as measured by PET, correlate with response to targeted experimental therapies. As a secondary goal, a molecular profile will be determined from surgical specimens of the primary tumor and from metastatic bone marrow biopsy material when available. The objective will be to associate non-invasive PET metabolic image data with differences in tumor phenotype measured by immunohistochemical markers such as Ki-67. p27, p53, cyclin 01, Glut transporters hexokinase, and androgen receptor .
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