Abstract 4322: Ligand-directed therapy and molecular imaging in a mouse model of androgen-independent osteogenic prostate cancer

Abstract

Abstract In working towards a theranostic approach in human prostate cancer, we have used in vivo phage display in a unique animal model of androgen-independent human osteoblastic bone metastases (animal model described by Li et al. J. Clin. Invest. 2008 Aug;118(8):2697-710) to uncover accessible targets and peptide ligands for molecular imaging and treatment. This unbiased combinatorial screening identified a peptide targeting Glucose-regulated Protein 78kDa (GRP78), a protein previously implicated in human cancer, including prostate cancer. By using a hybrid gene delivery vehicle consisting of phage capsid-proteins and AAV genomic elements (AAVP) we have successfully expressed thymidine kinase protein from Herpes Simplex Virus (HSVtk) for a gene-directed enzyme prodrug therapy (GDEPT) approach. In combination with 18FEAU as an imaging probe, the expression of this protein was monitored by Positron Emission Tomography (PET). After expression was confirmed, treatment with the prodrug gancyclovir was used to induce tumor-specific apoptosis. In a second approach, this ligand-receptor system was used to specifically and efficiently deliver small interfering RNA (siRNA) in vitro and in vivo. Both approaches clearly show that the newly identified peptide targeting GRP78 can be considered for targeted drug development against human metastatic androgen-independent osteogenic prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4322.