Comparison of a Minimally Invasive Transthoracic Approach and a Surgical Method For Intrapleural Injection of Tumor Cells in Mice

Abstract

Intrapleural injections can be used in mice to deliver therapeutic and diagnostic agents and to model human disease processes (for example, pleural fluid accumulation, malignant pleural disease, and lung cancers). In the context of establishing cancer models, minimally invasive methods of intrapleural injection are desirable because inflammation at the injection site can have a major impact on tumor growth and progression. Common approaches for intrapleural injection include surgical exposure of the thoracic wall or the diaphragm prior to injection; however, these invasive procedures require tissue dissection that triggers an undesirable inflammatory response and increases the risk of pneumothorax. While nonsurgical procedures can minimize this concern, ‘blind’ injections may lead to off target inoculation. In this study, we hypothesized that a minimally invasive transthoracic approach (MI-TT) would produce a tumor distribution and burden similar to that of a surgical transabdominal approach (SX-TA). Prior to performing the procedures on live mice, surgeons were trained using cadavers and terminal procedures. Then a total of 14 nude mice (female, 4 to 6 wk old) were injected with 50 μL (5 million) A549-Luc2 human cancer cells either using the MI-TT (n = 8) or SX-TA (n = 6) approach under carprofen analgesia and isoflurane anesthesia. Our results indicate that with training, a minimally invasive transthoracic approach for intrapleural injection provides more consistent tumor placement and a greater tumor burden than does the surgical method. However, additional studies are necessary to confirm anatomic placement and characterize tumor profiles.