Developing novel diagnostic and therapeutic strategy to manage metastasis is a pressing issue in cancer research. The presence of lymph node metastases is a poor prognostic indicator. We have developed the adenoviral test vector, AdTSTA-sr39tk, which is designed to express the herpes simplex thymidine kinase (sr39tk) gene under the control of a highly amplified prostate-specific PSA promoter system (TSTA). The sr39tk gene has the capacity to produce positron emitting tomography (PET) signal and induce toxicity to cancer cells. Adenoviral vectors are frequently taken up into the lymphatics and transported to regional lymph nodes. A main objective of this study is to evaluate whether the prostate-specific AdTSTA-sr39tk PET imaging reporter vector can detect disseminated prostate cancer cells in the regional lymph nodes. The hypothesis is that if prostate cancer cells have disseminated to the same lymph node as the viral vector, then gene transfer and expression in the cancer cells mediated by AdTSTA-sr39tk will produce a PET signal in the lymph node after the administration of the [18F]-FHBG radiotracer substrate. Due to the cell-restricted expression control in the vector, a positive PET signal would indicate that AdTSTA-sr39tk gene transfer has occurred in prostate cancer cells. The tumoral lymphangiogenesis and lymphatic metastasis will be induced in the PTEN-null murine prostate cancer model. This model will in turn be used to test the vector-mediated PET diagnostic strategy to detect lymph node metastases. The second objective is to apply the AdTSTAsr39tk in a PET-guided therapeutic strategy to treat pet dogs that developed spontaneous prostate cancer. PET imaging after intratumoral injection of the viral vector will provide the location and magnitude of test gene expression prior to initiation of cytotoxic therapy. Testing of the novel prostate-targeted diagnostic and therapeutic strategy in relevant small and large animal model will be very helpful to guide the future clinical protocol for managing disseminated prostate cancer. ? ? ?
