Endobronchial ultrasound-guided injection of NBTXR3 radioenhancing nanoparticles into mediastinal and hilar lymph nodes: A swine model to evaluate feasibility, injection technique, safety, nanoparticle retention and dispersion

Roberto F. Casal, Audra J. Schwalk, Natalie Fowlkes, Rebeca Romero Aburto, William Norton, Katherine A. Dixon, Steven Lin, Simona F. Shaitelman, Gouthami Chintalapani, Lori Hill

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Loco-regionally advanced lung cancer is typically treated with a combination of chemotherapy and radiation therapy, but overall survival and local control remain poor. Radio-enhancing nanoparticles such as NBTXR3 activated by radiotherapy results in increased cell death and potentially an anti-tumor immune response. The goal of this study was to assess the feasibility and safety of endobronchial ultrasound (EBUS)- guided injection of NBTXR3 into mediastinal and hilar lymph nodes (LN), as well as assess nanoparticle retention in the LN post-injection. Methods: Animals underwent bronchoscopy under general anesthesia with EBUS-guided injection of NBTXR3 into hilar and mediastinal LN. LN and injection volumes were calculated based on pre-injection computed tomography (CT) scans. CT scans were repeated at 5 min, 30 min, and 8 days post-injection. Blood-draws were also obtained at baseline and post-injection. Animals were then housed, monitored, and sacrificed 8 days post-injection. Necropsy was then performed with gross and histologic analysis of LN. Results: A total of 20 LN were injected in 5 pigs (4 LN per animal). Nanoparticles were retained in 100% of LN at 30 min, and 90% of LN at 8 days. Extravasation of nanoparticles was seen in 4 out of the 20 LN. There were no cases of nanoparticle embolization visible by CT in distant organs. Small air-bubbles were introduced in the targets and surrounding tissue in 3 out of 20 LN. Of note, at 8 days, none of these airbubbles were present on CT scan. There were no intra-procedural or post-procedural complications in either CT scans or necropsy findings. Pigs remained clinically stable and neither laboratory values nor necropsy showed evidence of inflammation. Conclusions: EBUS-guided injection of NBTXR3 radio-enhancing nanoparticles can be safely performed achieving a high rate of nanoparticle retention, low extravasation, and no visible nanoparticle embolization.

Original languageEnglish (US)
Pages (from-to)2317-2324
Number of pages8
JournalJournal of Thoracic Disease
Volume12
Issue number5
DOIs
StatePublished - May 1 2020
Externally publishedYes

Keywords

  • Endobronchial ultrasound (EBUS)
  • Hafnium oxide nanoparticles
  • Lung cancer
  • NBTXR3
  • Radiation therapy

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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