Enhanced Peptide Radiotherapy of Prostate Cancer Using Targeted Adenoviral Vectors

摘要

An adenovirus encoding the genes for human somatostatin receptor subtype 2 has been constructed and evaluated in human prostate cancer cells with regard to binding of 64Cu- octreotide. In vitro experiments were performed with DU-145 and PC-3 human prostate cancer cells. Expression levels of SSTR2 were determined using a 64Cu-octreotide saturation binding assay on cell membrane preparations. In vivo experiments were conducted in scid mice bearing subcutaneous DU-l45 or PC-3 cells. AdSSTR2 was injected intratumorally followed 48 h later by an i.v. injection of 64Cu-octreotide. The mice were sacrificed 1 h after peptide injection for biodistribution analysis. The expression of SSTR2 on DU-145 cells was 9485 fmol/mg after infection at 100 MOl compared to 3540 fmol/mg on PC-3 cells. In vivo biodistribution studies showed similar uptake of 64Cu-octreotide in both DU-l45 and PC-3 tumors after infection with AdSSTR2 (2.5 and 2.7% ID/g, respectively). This uptake was greater than that observed in tumors injected with control adenovirus (1.4 - 1.6% ID/g).