Feasibility of Combination Intra-arterial Yttrium-90 and Irinotecan Microspheres in the VX2 Rabbit Model

Andrew C. Gordon; Sarah B. White; Yihe Yang; Vanessa L. Gates; Daniel Procissi; Kathleen R. Harris; Zhuoli Zhang; Tianchu Lyu; Xiaoke Huang; Matthew R. Dreher; Reed A. Omary; Riad Salem; Robert J. Lewandowski; Andrew C. Larson

doi:10.1007/s00270-020-02538-x

Feasibility of Combination Intra-arterial Yttrium-90 and Irinotecan Microspheres in the VX2 Rabbit Model

Andrew C. Gordon^*, Sarah B. White, Yihe Yang, Vanessa L. Gates, Daniel Procissi, Kathleen R. Harris, Zhuoli Zhang, Tianchu Lyu, Xiaoke Huang, Matthew R. Dreher, Reed A. Omary, Riad Salem, Robert J. Lewandowski, Andrew C. Larson

^*Corresponding author for this work

Radiology

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5 Scopus citations

Abstract

Purpose: To evaluate the combination of ⁹⁰Y radioembolization (Y90) and drug-eluting bead irinotecan (DEBIRI) microspheres in the VX2 rabbit model. Materials and Methods: An initial dose finding study was performed in 6 White New Zealand rabbits to identify a therapeutic but subcurative dose of Y90. In total, 29 rabbits were used in four groups: Y90 treatment (n = 8), DEBIRI treatment (n = 6), Y90 + DEBIRI treatment (n = 7), and an untreated control group (n = 8). Hepatic toxicity was evaluated at baseline, 24 h, 72 h, 1 week, and 2 weeks. MRI tumor volume (TV) and enhancing tumor volume were assessed baseline and 2 weeks. Tumor area and necrosis were evaluated on H&E for pathology. Results: Infused activities of 84.0–94.4 MBq (corresponding to 55.1–72.7 Gy) were selected based on the initial dose finding study. Infusion of DEBIRI after Y90 was technically feasible in all cases (7/7). Overall, 21/29 animals survived to 2 weeks, and the remaining animals had extrahepatic disease on necropsy. Liver transaminases were elevated with Y90, DEBIRI, and Y90 + DEBIRI compared to control at 24 h, 72 h, and 1 week post-treatment and returned to baseline by 2 weeks. By TV, Y90 + DEBIRI was the only treatment to show statistically significant reduction at 2 weeks compared to the control group (p = 0.012). The change in tumor volume (week 2—baseline) for both Y90 + DEBIRI versus control (p = 0.002) and Y90 versus control (p = 0.014) was significantly decreased. There were no statistically significant differences among groups on pathology. Conclusion: Intra-arterial Y90 + DEBIRI was safe and demonstrated enhanced antitumor activity in rabbit VX2 tumors. This combined approach warrants further investigation.

Original language	English (US)
Pages (from-to)	1528-1537
Number of pages	10
Journal	Cardiovascular and Interventional Radiology
Volume	43
Issue number	10
DOIs	https://doi.org/10.1007/s00270-020-02538-x
State	Published - Oct 1 2020

Funding

The authors thank Northwestern University Healthy Physics (Jose Macatangay, Joseph Princewill, Thomas E. Whittenhall Jr., Angelica E. Gheen). Animal housing and husbandry was provided by the Center for Comparative Medicine (Dr. Stephen I. Levin, Giovanni Pompilio). Imaging for our studies was made possible by Northwestern University's Center for Translational Imaging (Daniel Procissi, Sol Misener). Survival studies were supported through dedicated housing and accommodation by the Center for Comparative Medicine (Dr. Stephen I. Levin, Giovanni Pompilio). We are grateful for the generous funding provided by the SIR Foundation Allied Scientist Grant (ACG) and the Department of Radiology of the Feinberg School of Medicine. ACG Medical Scientist Training Program (T32GM008152). Dose vials, administration kits, and additional funding for research materials were provided through a research grant from BTG. RS is supported in part by NIH grant CA126809. SBW receives salary support from NIH grant 5R25 CA 132822-03 and a RSNA Foundation Research Scholar Grant. The listed authors performed data collection, analysis, and manuscript preparation independently without assistance from funding sources. Histology services were provided by the Northwestern University Mouse Histology and Phenotyping Laboratory which is supported by NCI P30-CA060553 and the Robert H Lurie Comprehensive Cancer Center Pathology Core Facility (Bernice Frederick, Adriana Rosca, Demirkan Gürsel). Acknowledgements

Keywords

Chemoembolization
Irinotecan
Magnetic resonance imaging
Radioembolization
Yttrium-90

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging
Cardiology and Cardiovascular Medicine

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10.1007/s00270-020-02538-x

Cite this

Gordon, A. C., White, S. B., Yang, Y., Gates, V. L., Procissi, D., Harris, K. R., Zhang, Z., Lyu, T., Huang, X., Dreher, M. R., Omary, R. A., Salem, R., Lewandowski, R. J., & Larson, A. C. (2020). Feasibility of Combination Intra-arterial Yttrium-90 and Irinotecan Microspheres in the VX2 Rabbit Model. Cardiovascular and Interventional Radiology, 43(10), 1528-1537. https://doi.org/10.1007/s00270-020-02538-x

@article{b3babee44cf54fe8a5eb1d6c0ee0c519,

title = "Feasibility of Combination Intra-arterial Yttrium-90 and Irinotecan Microspheres in the VX2 Rabbit Model",

abstract = "Purpose: To evaluate the combination of 90Y radioembolization (Y90) and drug-eluting bead irinotecan (DEBIRI) microspheres in the VX2 rabbit model. Materials and Methods: An initial dose finding study was performed in 6 White New Zealand rabbits to identify a therapeutic but subcurative dose of Y90. In total, 29 rabbits were used in four groups: Y90 treatment (n = 8), DEBIRI treatment (n = 6), Y90 + DEBIRI treatment (n = 7), and an untreated control group (n = 8). Hepatic toxicity was evaluated at baseline, 24 h, 72 h, 1 week, and 2 weeks. MRI tumor volume (TV) and enhancing tumor volume were assessed baseline and 2 weeks. Tumor area and necrosis were evaluated on H&E for pathology. Results: Infused activities of 84.0–94.4 MBq (corresponding to 55.1–72.7 Gy) were selected based on the initial dose finding study. Infusion of DEBIRI after Y90 was technically feasible in all cases (7/7). Overall, 21/29 animals survived to 2 weeks, and the remaining animals had extrahepatic disease on necropsy. Liver transaminases were elevated with Y90, DEBIRI, and Y90 + DEBIRI compared to control at 24 h, 72 h, and 1 week post-treatment and returned to baseline by 2 weeks. By TV, Y90 + DEBIRI was the only treatment to show statistically significant reduction at 2 weeks compared to the control group (p = 0.012). The change in tumor volume (week 2—baseline) for both Y90 + DEBIRI versus control (p = 0.002) and Y90 versus control (p = 0.014) was significantly decreased. There were no statistically significant differences among groups on pathology. Conclusion: Intra-arterial Y90 + DEBIRI was safe and demonstrated enhanced antitumor activity in rabbit VX2 tumors. This combined approach warrants further investigation.",

keywords = "Chemoembolization, Irinotecan, Magnetic resonance imaging, Radioembolization, Yttrium-90",

author = "Gordon, {Andrew C.} and White, {Sarah B.} and Yihe Yang and Gates, {Vanessa L.} and Daniel Procissi and Harris, {Kathleen R.} and Zhuoli Zhang and Tianchu Lyu and Xiaoke Huang and Dreher, {Matthew R.} and Omary, {Reed A.} and Riad Salem and Lewandowski, {Robert J.} and Larson, {Andrew C.}",

note = "Funding Information: The authors thank Northwestern University Healthy Physics (Jose Macatangay, Joseph Princewill, Thomas E. Whittenhall Jr., Angelica E. Gheen). Animal housing and husbandry was provided by the Center for Comparative Medicine (Dr. Stephen I. Levin, Giovanni Pompilio). Imaging for our studies was made possible by Northwestern University's Center for Translational Imaging (Daniel Procissi, Sol Misener). Survival studies were supported through dedicated housing and accommodation by the Center for Comparative Medicine (Dr. Stephen I. Levin, Giovanni Pompilio). Funding Information: We are grateful for the generous funding provided by the SIR Foundation Allied Scientist Grant (ACG) and the Department of Radiology of the Feinberg School of Medicine. ACG Medical Scientist Training Program (T32GM008152). Dose vials, administration kits, and additional funding for research materials were provided through a research grant from BTG. RS is supported in part by NIH grant CA126809. SBW receives salary support from NIH grant 5R25 CA 132822-03 and a RSNA Foundation Research Scholar Grant. The listed authors performed data collection, analysis, and manuscript preparation independently without assistance from funding sources. Histology services were provided by the Northwestern University Mouse Histology and Phenotyping Laboratory which is supported by NCI P30-CA060553 and the Robert H Lurie Comprehensive Cancer Center Pathology Core Facility (Bernice Frederick, Adriana Rosca, Demirkan G{\"u}rsel). Acknowledgements Funding Information: RAO and ACL are founders and owners of IO-RAD and received grant funding from BTG for this study. SBW is a consultant for IO-RAD and Guerbet, and receives research support from Siemens and Guerbet. RJL and RS served as scientific advisors to BTG. RJL is a consultant for ABK. MRD is an employee of BTG. None of the other authors have identified any conflict of interest. Publisher Copyright: {\textcopyright} 2020, Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).",

year = "2020",

month = oct,

day = "1",

doi = "10.1007/s00270-020-02538-x",

language = "English (US)",

volume = "43",

pages = "1528--1537",

journal = "Cardiovascular and Interventional Radiology",

issn = "0174-1551",

publisher = "Springer Verlag",

number = "10",

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Gordon, AC, White, SB, Yang, Y, Gates, VL, Procissi, D, Harris, KR, Zhang, Z, Lyu, T, Huang, X, Dreher, MR, Omary, RA, Salem, R , Lewandowski, RJ & Larson, AC 2020, 'Feasibility of Combination Intra-arterial Yttrium-90 and Irinotecan Microspheres in the VX2 Rabbit Model', Cardiovascular and Interventional Radiology, vol. 43, no. 10, pp. 1528-1537. https://doi.org/10.1007/s00270-020-02538-x

TY - JOUR

T1 - Feasibility of Combination Intra-arterial Yttrium-90 and Irinotecan Microspheres in the VX2 Rabbit Model

AU - Gordon, Andrew C.

AU - White, Sarah B.

AU - Yang, Yihe

AU - Gates, Vanessa L.

AU - Procissi, Daniel

AU - Harris, Kathleen R.

AU - Zhang, Zhuoli

AU - Lyu, Tianchu

AU - Huang, Xiaoke

AU - Dreher, Matthew R.

AU - Omary, Reed A.

AU - Salem, Riad

AU - Lewandowski, Robert J.

AU - Larson, Andrew C.

N1 - Funding Information: The authors thank Northwestern University Healthy Physics (Jose Macatangay, Joseph Princewill, Thomas E. Whittenhall Jr., Angelica E. Gheen). Animal housing and husbandry was provided by the Center for Comparative Medicine (Dr. Stephen I. Levin, Giovanni Pompilio). Imaging for our studies was made possible by Northwestern University's Center for Translational Imaging (Daniel Procissi, Sol Misener). Survival studies were supported through dedicated housing and accommodation by the Center for Comparative Medicine (Dr. Stephen I. Levin, Giovanni Pompilio). Funding Information: We are grateful for the generous funding provided by the SIR Foundation Allied Scientist Grant (ACG) and the Department of Radiology of the Feinberg School of Medicine. ACG Medical Scientist Training Program (T32GM008152). Dose vials, administration kits, and additional funding for research materials were provided through a research grant from BTG. RS is supported in part by NIH grant CA126809. SBW receives salary support from NIH grant 5R25 CA 132822-03 and a RSNA Foundation Research Scholar Grant. The listed authors performed data collection, analysis, and manuscript preparation independently without assistance from funding sources. Histology services were provided by the Northwestern University Mouse Histology and Phenotyping Laboratory which is supported by NCI P30-CA060553 and the Robert H Lurie Comprehensive Cancer Center Pathology Core Facility (Bernice Frederick, Adriana Rosca, Demirkan Gürsel). Acknowledgements Funding Information: RAO and ACL are founders and owners of IO-RAD and received grant funding from BTG for this study. SBW is a consultant for IO-RAD and Guerbet, and receives research support from Siemens and Guerbet. RJL and RS served as scientific advisors to BTG. RJL is a consultant for ABK. MRD is an employee of BTG. None of the other authors have identified any conflict of interest. Publisher Copyright: © 2020, Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).

PY - 2020/10/1

Y1 - 2020/10/1

N2 - Purpose: To evaluate the combination of 90Y radioembolization (Y90) and drug-eluting bead irinotecan (DEBIRI) microspheres in the VX2 rabbit model. Materials and Methods: An initial dose finding study was performed in 6 White New Zealand rabbits to identify a therapeutic but subcurative dose of Y90. In total, 29 rabbits were used in four groups: Y90 treatment (n = 8), DEBIRI treatment (n = 6), Y90 + DEBIRI treatment (n = 7), and an untreated control group (n = 8). Hepatic toxicity was evaluated at baseline, 24 h, 72 h, 1 week, and 2 weeks. MRI tumor volume (TV) and enhancing tumor volume were assessed baseline and 2 weeks. Tumor area and necrosis were evaluated on H&E for pathology. Results: Infused activities of 84.0–94.4 MBq (corresponding to 55.1–72.7 Gy) were selected based on the initial dose finding study. Infusion of DEBIRI after Y90 was technically feasible in all cases (7/7). Overall, 21/29 animals survived to 2 weeks, and the remaining animals had extrahepatic disease on necropsy. Liver transaminases were elevated with Y90, DEBIRI, and Y90 + DEBIRI compared to control at 24 h, 72 h, and 1 week post-treatment and returned to baseline by 2 weeks. By TV, Y90 + DEBIRI was the only treatment to show statistically significant reduction at 2 weeks compared to the control group (p = 0.012). The change in tumor volume (week 2—baseline) for both Y90 + DEBIRI versus control (p = 0.002) and Y90 versus control (p = 0.014) was significantly decreased. There were no statistically significant differences among groups on pathology. Conclusion: Intra-arterial Y90 + DEBIRI was safe and demonstrated enhanced antitumor activity in rabbit VX2 tumors. This combined approach warrants further investigation.

AB - Purpose: To evaluate the combination of 90Y radioembolization (Y90) and drug-eluting bead irinotecan (DEBIRI) microspheres in the VX2 rabbit model. Materials and Methods: An initial dose finding study was performed in 6 White New Zealand rabbits to identify a therapeutic but subcurative dose of Y90. In total, 29 rabbits were used in four groups: Y90 treatment (n = 8), DEBIRI treatment (n = 6), Y90 + DEBIRI treatment (n = 7), and an untreated control group (n = 8). Hepatic toxicity was evaluated at baseline, 24 h, 72 h, 1 week, and 2 weeks. MRI tumor volume (TV) and enhancing tumor volume were assessed baseline and 2 weeks. Tumor area and necrosis were evaluated on H&E for pathology. Results: Infused activities of 84.0–94.4 MBq (corresponding to 55.1–72.7 Gy) were selected based on the initial dose finding study. Infusion of DEBIRI after Y90 was technically feasible in all cases (7/7). Overall, 21/29 animals survived to 2 weeks, and the remaining animals had extrahepatic disease on necropsy. Liver transaminases were elevated with Y90, DEBIRI, and Y90 + DEBIRI compared to control at 24 h, 72 h, and 1 week post-treatment and returned to baseline by 2 weeks. By TV, Y90 + DEBIRI was the only treatment to show statistically significant reduction at 2 weeks compared to the control group (p = 0.012). The change in tumor volume (week 2—baseline) for both Y90 + DEBIRI versus control (p = 0.002) and Y90 versus control (p = 0.014) was significantly decreased. There were no statistically significant differences among groups on pathology. Conclusion: Intra-arterial Y90 + DEBIRI was safe and demonstrated enhanced antitumor activity in rabbit VX2 tumors. This combined approach warrants further investigation.

KW - Chemoembolization

KW - Irinotecan

KW - Magnetic resonance imaging

KW - Radioembolization

KW - Yttrium-90

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AN - SCOPUS:85086452122

SN - 0174-1551

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EP - 1537

JO - Cardiovascular and Interventional Radiology

JF - Cardiovascular and Interventional Radiology

IS - 10

ER -

Feasibility of Combination Intra-arterial Yttrium-90 and Irinotecan Microspheres in the VX2 Rabbit Model

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