Consistent with above results, N CADHERIN expression was undetectable in both

Males who are castrated Maraviroc 376348-65-1 at a young age do not develop prostate cancer, implying that androgens are risk factors for prostate cancer development. Approximately 8090% of prostate cancers are androgen dependent upon initial diagnosis, and endocrine therapy of prostate cancer is directed toward the reduction of serum an drogens and inhibition of AR. On the other hand, some very aggressive forms of prostate cancer lose AR expression and are insensitive to inhibition of the AR. Although AR is a specific target for prostate cancer treatment, loss of expression of AR has been observed in several aggressive tumors. Therefore, it is critical to determine its role in individual patients to guide and monitor treatment modalities. DHT was labeled with fluorine 18 to give 16b fluoro 5a dihydrotestoster one, which competes with DHT for binding to AR.<br><br> Larson et al. reported on a comparative clinical study of seven castrated patients with low circulating testosterone levels who had pro gressive metastatic prostate cancer and were imaged with FDG and FDHT. FDG uptake was positive in buy MK-2206 97% of the lesions with SUVmax of 5. 22, whereas FDHT was positive in 78% of the lesions with SUVmax of 5. 28, and FDHT also displayed heterogeneity in accumulation at different areas of the tumors. The reason for heteroge neity of tracer uptake in this study is unknown but might be because of the variation in AR expression versus glucose metabolism rate. Such heterogeneity might be indicative of prostate cancer and should be evaluated for response to therapy and disease progression.<br><br> Two patients in this study were under testosterone mTOR 活性化 treatment and had diminished FDHT uptake at the tumor site as expected. In another scan done to a patient treated with an Hsp90 inhibitor that indirectly reduces cellular concentration of AR, new lesions were detected by both FDG and FDHT in scans that were performed 45 weeks postinitial scans. FDHT was further evaluated in patients with progressive metastatic castration resistant pros tate cancer. The patients re ceived different doses of an AR antagonist, MDV3100, which inhibits AR nuclear translocation and subsequent binding to the response element on the DNA. Patients underwent PET scans before and 4 weeks after treatment with MDV3100 was initiated. PET imaging showed a decrease in FDHT uptake in all patients who received treatment compared with scans done before therapy.<br><br> An obstacle for interpreting these results and for imaging AR post MDV3100 treatment is that the antagonist prevents the binding of FDHT to AR. Therefore, in this setting, the best use of FDHT is as a method for evaluating the optimal dose of antiandrogen required for complete blockade of the AR, on a patient by patient basis. Another promising PET tracer reflecting the down stream effects of AR signaling is the monoclonal antibody, J591, that targets the extracellular domain of prostate specific membrane antigen. PSMA is a trans membrane glycoprotein mainly expressed on benign and malignant prostatic epithelial cells, and its expression level was found to correlate with tumor aggression, metastatic spread, and the development of castration resistance or resistance to hormone based therapies.