Abstract / Summary
Introduction Cisplatin has been a standard chemotherapeutic agent for advanced non-small cell lung cancer for decades. Conventionally administered intravenously, it undergoes systemic distribution, exposing both tumour and healthy tissues to the drug. Endobronchial ultrasound-guided transbronchial needle injection of cisplatin is emerging as a potential intratumoural drug delivery (ITDD) strategy. However, rigorous preclinical research is needed before ITDD can be more widely adopted. Methods We used our experimentally induced ovine pulmonary adenocarcinoma (OPA) model, generated by Jaagsiekte sheep retrovirus (JSRV) infection, to evaluate transthoracic and transbronchial ITDD techniques. We compared systemic platinum exposure following intravenous cisplatin delivery with that following intratumoural cisplatin administration. Both non-recovery and recovery studies were conducted in a total of eight sheep. Results ITDD techniques were successfully developed and performed in three tumour bearing sheep during non-recovery procedures. To provide a reference for systemic platinum exposure, intravenous cisplatin was administered to three JSRV-infected sheep that did not develop OPA. Intravenous administration produced a rapid plasma platinum peak followed by a rapid decline. ITDD resulted in preferential platinum deposition within targeted lung tumours while producing substantially lower systemic platinum exposure compared with intravenous administration. Intratumoural cisplatin delivery was also evaluated in a recovery procedure using a single sheep, comparing single-site and fractionated administration over a 28-day period, with tumour biopsies confirming lesion presence before treatment. Following ITDD, tumour volumes were observed to decrease over the study period. The recovery experiments demonstrated the feasibility of repeated tumour biopsies, intratumoural injections, longitudinal CT monitoring and recovery anaesthesia using the OPA model. Discussion To our knowledge, this is the first report of direct intratumoural cisplatin administration into ovine lung tumours. This study also provides proof-of-concept that this clinically relevant large animal lung cancer model can serve as a translational platform for evaluating intratumoural therapeutic delivery strategies relevant to human lung cancer.