Preclinical imaging for establishment and comparison of orthotopic Non-Small Cell Lung Carcinoma: In search for models reflecting clinical scenarios


Preclinical imaging for establishment and comparison of orthotopic Non-Small Cell Lung Carcinoma: In search for models reflecting clinical scenarios

Aktar, R.; Dietrich, A.; Tillner, F.; Kotb, S.; Löck, S.; Willers, H.; Baumann, M.; Krause, M.; Bütof, R.

Objectives:

Clinically relevant animal models of non-small cell lung carcinoma (NSCLC) are required for the validation of novel treatments. We compared two different orthotopic transplantation techniques as well as imaging modalities to identify suitable mouse models mimicking clinical scenarios.
Methods:
We used three genomically diverse NSCLC cell lines (NCI-H1703 adenosquamous cell carcinoma, NCI-H23 adenocarcinoma and A549 adenocarcinoma) for implanting tumour cells either as spheroids or cell suspension into lung parenchyma. Bioluminescence imaging (BLI) and contrast-enhanced cone beam computed tomography (CBCT) were performed twice weekly to monitor tumour growth. Tumour histological data and microenvironmental parameters were determined.
Results:
Tumour development after spheroid-based transplantation differs probably due to the integrity of spheroids, as H1703 developed single localized nodules, whereas H23 showed diffuse metastatic spread starting early after transplantation. A549 transplantation as cell suspension with the help of a stereotactic system was associated with initial single localized tumour growth and eventual metastatic spread. Imaging techniques were successfully applied to monitor longitudinal tumour growth: BLI revealed highly sensitive qualitative data, whereas CBCT was associated with less sensitive quantitative data. Histology revealed significant model dependent heterogeneity in proliferation, hypoxia, perfusion and necrosis.
Conclusions:
Our developed orthotopic NSCLC tumours have similarity with biological growth behavior similar to that seen in the clinic and could therefore be used as attractive models to study tumour biology and evaluate new therapeutic strategies. The use of human cancer cell lines facilitates testing of different genomic tumor profiles that may affect treatment outcomes.
Advances in knowledge:
The combination of different imaging modalities and orthotopic transplantation techniques pave the way towards representative preclinical NSCLC models for experimental testing of novel therapeutic options in future studies.

Keywords: Non-small cell lung cancer; orthotopic model; transplantation technique; preclinical imaging; microenvironment

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Permalink: https://www.hzdr.de/publications/Publ-27590
Publ.-Id: 27590