TY - JOUR
T1 - Endobronchial ultrasound-guided injection of NBTXR3 radioenhancing nanoparticles into mediastinal and hilar lymph nodes
T2 - A swine model to evaluate feasibility, injection technique, safety, nanoparticle retention and dispersion
AU - Casal, Roberto F.
AU - Schwalk, Audra J.
AU - Fowlkes, Natalie
AU - Aburto, Rebeca Romero
AU - Norton, William
AU - Dixon, Katherine A.
AU - Lin, Steven
AU - Shaitelman, Simona F.
AU - Chintalapani, Gouthami
AU - Hill, Lori
N1 - Funding Information:
We sincerely thank Jennifer Meyer, Robin Harmon, and Stephanie Mayor for providing anesthesia and overall animal care, Taylor Lee Jr. for his assistance with bronchoscopy, and Keith A. Michel for his assistance in image processing. Our study would have not been possible without their help. We would also like to thank the John S Dunn Research Foundation Center for Radiological Sciences for providing imaging and lab support. Funding: This study was sponsored by Nanobiotix and in part by the National Institute of Health through MD Anderson’s Cancer Center Support Grant CA016672.
Publisher Copyright:
© Journal of Thoracic Disease. All rights reserved.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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.
AB - 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.
KW - Endobronchial ultrasound (EBUS)
KW - Hafnium oxide nanoparticles
KW - Lung cancer
KW - NBTXR3
KW - Radiation therapy
UR - http://www.scopus.com/inward/record.url?scp=85086024763&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85086024763&partnerID=8YFLogxK
U2 - 10.21037/jtd.2020.03.100
DO - 10.21037/jtd.2020.03.100
M3 - Article
C2 - 32642136
AN - SCOPUS:85086024763
SN - 2072-1439
VL - 12
SP - 2317
EP - 2324
JO - Journal of Thoracic Disease
JF - Journal of Thoracic Disease
IS - 5
ER -