Endobronchial ultrasound-guided injection of NBTXR3 radio-enhancing 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

doi:10.21037/jtd.2020.03.100

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

J Thorac Dis. 2020 May;12(5):2317-2324. doi: 10.21037/jtd.2020.03.100.

Affiliations

¹ Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
² Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
³ Nanobiotix SA, Paris, France.
⁴ John S. Dunn Center for Radiological Sciences, Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
⁵ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
⁶ Siemens Medical Solutions USA Inc., Malvern, PA, USA.

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 air-bubbles 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.

Keywords: Lung cancer; NBTXR3; endobronchial ultrasound (EBUS); hafnium oxide nanoparticles; radiation therapy.

Grants and funding

P30 CA016672/CA/NCI NIH HHS/United States