An orthotopic non-small cell lung cancer model for image-guided small animal radiotherapy platforms

Venus Sosa Iglesias, Stefan J. van Hoof, Ana Vaniqui, Lotte Ejr Schyns, Natasja Lieuwes, Ala Yaromina, Linda Spiegelberg, Arjan J. Groot, Frank Verhaegen, Jan Theys, Ludwig Dubois*, Marc Vooijs*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Objective: Lung cancer is the deadliest cancer worldwide. To increase treatment potential for lung cancer, pre-clinical models that allow testing and follow up of clinically relevant treatment modalities are essential. Therefore, we developed a single-nodule-based orthotopic non-small cell lung cancer tumor model which can be monitored using multimodal non-invasive imaging to select the optimal image-guided radiation treatment plan.

Methods: An orthotopic non-small cell lung cancer model in NMRI-nude mice was established to investigate the complementary information acquired from 80 kVp microcone-beam CT (micro-CBCT) and bioluminescence imaging (BLI) using different angles and filter settings. Different micro-CBCT-based radiation-delivery plans were evaluated based on their dose-volume histogram metrics of tumor and organs at risk to select the optimal treatment plan.

Results: H1299 cell suspensions injected directly into the lung render exponentially growing single tumor nodules whose CBCT-based volume quantification strongly correlated with BLI-integrated intensity. Parallel-opposed single angle beam plans through a single lung are preferred for smaller tumors, whereas for larger tumors, plans that spread the radiation dose across healthy tissues are favored.

Conclusions: Closely mimicking a clinical setting for lung cancer with highly advanced preclinical radiation treatment planning is possible in mice developing orthotopic lung tumors.

Advances in knowledge: BLI and CBCT imaging of orthotopic lung tumors provide complementary information in a temporal manner. The optimal radiotherapy plan is tumor volume-dependent.

Original languageEnglish
Article number20180476
Number of pages10
JournalBritish Journal of Radiology
Volume92
Issue number1095
DOIs
Publication statusPublished - 2019

Keywords

  • MICROCOMPUTED TOMOGRAPHY
  • TUMOR MICROENVIRONMENT
  • RADIATION-THERAPY
  • PROGRESSION
  • SMART
  • RESISTANCE
  • QUALITY
  • GROWTH

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