A large animal lung cancer model for the evaluation of intratumoural cisplatin delivery strategies
5 affiliations
- 1The Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh , ,
- 2Moredun Research Institute, Pentlands Science Park , ,
- 3The School of Chemistry, University of Edinburgh , ,
- 4The School of Geoscience, University of Edinburgh , ,
- 5Interventional Oncology, Johnson & Johnson Enterprise Innovation, Inc. , , ,
Abstract
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.
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BibTeX
@article{meehan2026large,
title = {{A large animal lung cancer model for the evaluation of intratumoural cisplatin delivery strategies}},
author = {James Meehan and David Collie and Ziyuan Chang and Rachael Gregson and R. Eddie Clutton and Stephen N. Greenhalgh and Lynn Grant and Sara Kennedy and James Nixon and Chris Cousens and Helen Todd and Jennifer Savage and Jo Moore and David J. Griffiths and Lorna J. Eades and Gavin Sim and Nicole Storer and Chad E. Eckert and Mark Gray},
journal = {Frontiers in oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1906629},
url = {https://europepmc.org/article/PMC/PMC13691547},
note = {CC BY},
}
RIS
TY - JOUR
TI - A large animal lung cancer model for the evaluation of intratumoural cisplatin delivery strategies
AU - James Meehan
AU - David Collie
AU - Ziyuan Chang
AU - Rachael Gregson
AU - R. Eddie Clutton
AU - Stephen N. Greenhalgh
AU - Lynn Grant
AU - Sara Kennedy
AU - James Nixon
AU - Chris Cousens
AU - Helen Todd
AU - Jennifer Savage
AU - Jo Moore
AU - David J. Griffiths
AU - Lorna J. Eades
AU - Gavin Sim
AU - Nicole Storer
AU - Chad E. Eckert
AU - Mark Gray
PY - 2026
DA - 2026/10/09
JO - Frontiers in oncology
DO - 10.3389/fonc.2026.1906629
UR - https://europepmc.org/article/PMC/PMC13691547
AB - 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.
SN - 2234-943X
ER -