Development of a Large Animal Model for Lung Tumors

Abstract

Minimally invasive locoregional therapies for human liver tumors have been developed in recent years, and similar treatment options may be successful in the management of human lung cancer. Our goal was to develop a lung tumor model in a large animal to simulate human lung cancer for preclinical assessment of novel therapeutic options. Fresh canine transmissible venereal tumor (cTVT) fragments were inoculated into the lungs of 10 dogs by intraarterial (n = 2) or percutaneous (n = 8) methods. Cyclosporin was administered to produce immunosuppression in nine of the dogs. Tumor growth was monitored at regular intervals (every 1-2 weeks) by computed tomography. All animals were killed between 6 and 10 weeks after inoculation; complete necropsy examinations were performed and appropriate tissues were removed for gross and histopathologic evaluation. Administration of tumor fragments into the right apical pulmonary artery resulted in the development of more than 20 well-defined scattered pulmonary nodules in the affected lung segment. Nodules grew to a maximum diameter of 12 mm in 10 weeks. Percutaneous inoculation of tumor fragments resulted in more predictable growth of solitary tumors (range, 7-35 mm in diameter) in the transplantation bed. No tumor growth was observed in the dog that did not receive cyclosporin. Percutaneous inoculation and intraarterial transplantation of cTVT fragments in the canine lung result in predictable patterns of tumor growth resembling the solitary pulmonary nodules and metastatic disease found in humans. In addition, cyclosporin administration may be necessary to promote growth of viable tumor.