1. ¹Department of Medical Biochemistry and Molecular Biology, School of Medicine, University of Limoges, 87025 Limoges, France
2. ²Department of Nuclear Medicine, School of Medicine, University of Limoges, 87025 Limoges, .France
3. ³Department of Anatomopathology, School of Medicine, University of Limoges, 87025 Limoges, France
4. ⁴Department of Orthopedic Surgery, School of Medicine, University of Limoges, 87025 Limoges, France
5. ⁵Department of Research and Development, Munich Biotech AG, Forstenriederstrasse 10, 82061 Neuried, Germany

Correspondence: Michel Rigaud, Fax: +33 5 55 05 64 02. E-mail: rigaud@unilim.fr

Received 24 April 2004; Accepted 5 October 2004.

Abstract

Antiangiogenesis or destruction of tumor neovessels is an effective strategy to prevent tumor growth. Endostatin, one of the many inhibitors of angiogenesis that have been discovered, has shown conflicting results in preclinical assays. We studied the therapeutic potential of lipid/DNA complexes consisting of cationic liposomes and an endostatin-coding plasmid (Endo cDNA/CLP) in an orthotopic osteosarcoma model in rats. Empty plasmid without the endostatin gene complexed with cationic liposomes served as control. Animals were treated intravenously three times a week starting on the day tumors were detectable by ¹⁸FDG tomoscintigraphy. During treatment, tumor progression was followed by PET scan and angioscintigraphy, and the effects of antivascular therapy on primary tumor, metastases, and tumor vascular density were confirmed by histologic analysis. Our results demonstrate that therapy using Endo cDNA/CLP is associated with pronounced delay in tumor growth. Moreover, it effectively prevented the occurrence of lung metastases, the major reason for bad prognosis and death in osteosarcoma patients. This approach could be used as an adjuvant therapy for osteosarcoma.