Radionuclide Reporter Gene Imaging And Therapy Of Pancreatic Cancer Xenografts Induced To Express Somatostatin Receptor 2 By Gene Transfer

Background & Objective: Somatostatin is a widely distributed peptidethat negatively regulates multiple physiological functions. Somatostatin inhibits cell proliferation and growth hormone secretion through interaction with somatostatin receptors (SSTRs). Five SSTRs have been cloned in the human, among those SSTRs, the SSTR2 gene is found to be the most important SSTR subtype for tumors. Many studies have demonstrated tumor cell growth inhibition by somatostatin and somatostatin analogs in SSTR2-positive tumors. However, functional SSTR2 are lost in most pancreatic cancers. Loss of SSTR2 expression may lead to a deficiency in negative regulation of cell growth by somatostatin analogs. Accordingly, gene therapy may be a promising strategy. Treating pancreatic cancer by reintroducing SSTR2 gene back to the cancer cells may be a good way. To evaluate the efficiency of gene therapy, it is requisite to monitor localization and expression of the therapeutic gene in vivo. Radionuclide reporter gene imaging techniques are currently being developed to map the topography and level of gene expression following gene therapy. Reporter gene can be used to monitor therapeutic gene and the efficacy of transgene targeting and transduction. SSTR2 is under evaluation as a reporter gene. The reporter SSTR2 protein is expressed on the plasma membrane of target cells and detected by imaging the specific accumulation of radiolabeled somatostatin analogs. The expression of therapeutic gene was indirectly evaluated through the expression of SSTR2 gene. In the course of gene therapy using SSTR2 in pancreatic cancer, SSTR2, the therapeutic gene also function as a reporter gene. Thus in the present study we established a radionuclide reporter gene imaging technology for monitoring adenoviral-mediated SSTR2 gene transfer to pancreatic cancer xenografts and wanted to supply a new way to evaluate the effects of gene therapy in pancreatic cancer. Furthermore, we also...