Yttrium-90 Radioembolization and Tumor Hypoxia: Gas-challenge BOLD Imaging in the VX2 Rabbit Model of Hepatocellular Carcinoma

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

doi:10.1016/j.acra.2020.04.012

Yttrium-90 Radioembolization and Tumor Hypoxia: Gas-challenge BOLD Imaging in the VX2 Rabbit Model of Hepatocellular Carcinoma

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

^*Corresponding author for this work

Radiology

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Rationale and Objectives: To use a rapid gas-challenge blood oxygen-level dependent magnetic resonance imaging exam to evaluate changes in tumor hypoxia after ⁹⁰Y radioembolization (Y90) in the VX2 rabbit model. Materials and Methods: White New Zealand rabbits (n = 11) provided a Y90 group (n = 6 rabbits) and untreated control group (n = 5 rabbits). R2* maps were generated with gas-challenges (O₂/room air) at baseline, 1 week, and 2 weeks post-Y90. Laboratory toxicity was evaluated at baseline, 24 hours, 72 hours, 1 hours, and 2 weeks. Histology was used to evaluate tumor necrosis on hematoxylin and eosin and immunofluorescence imaging was used to assess microvessel density (CD31) and proliferative index (Ki67). Results: At baseline, median tumor volumes and time to imaging were similar between groups (p = 1.000 and p = 0.4512, respectively). The median administered dose was 50.4 Gy (95% confidence interval:44.8–55.9). At week 2, mean tumor volumes were 5769.8 versus 643.7 mm³ for control versus Y90 rabbits, respectively (p = 0.0246). At two weeks, ΔR2* increased for control tumors to 12.37 ± 12.36sec⁻¹ and decreased to 4.48 ± 9.00sec⁻¹ after Y90. The Pearson correlation coefficient for ΔR2* at baseline and percent increase in tumor size by two weeks was 0.798 for the Y90 group (p = 0.002). There was no difference in mean microvessel density for control versus Y90 treated tumors (p = 0.6682). The mean proliferative index was reduced in Y90 treated tumors at 30.5% versus 47.5% for controls (p = 0.0071). Conclusion: The baseline ΔR2* of tumors prior to Y90 may be a predictive imaging biomarker of tumor response and treatment of these tumors with Y90 may influence tumor oxygenation over time.

Original language	English (US)
Pages (from-to)	849-858
Number of pages	10
Journal	Academic radiology
Volume	28
Issue number	6
DOIs	https://doi.org/10.1016/j.acra.2020.04.012
State	Published - Jun 2021

Funding

Funding: 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 an Investigator Initiated Study (IIS) 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). Funding: 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 an Investigator Initiated Study (IIS) 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?rsel).

Keywords

Hepatic radioembolization
Magnetic resonance imaging
Oxygenation
Yttrium-90

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.acra.2020.04.012

Cite this

Gordon, A. C., White, S. B., Gates, V. L., Procissi, D., Harris, K. R., Yang, Y., Zhang, Z., Li, W., Lyu, T., Huang, X., Omary, R. A., Salem, R., Lewandowski, R. J., & Larson, A. C. (2021). Yttrium-90 Radioembolization and Tumor Hypoxia: Gas-challenge BOLD Imaging in the VX2 Rabbit Model of Hepatocellular Carcinoma. Academic radiology, 28(6), 849-858. https://doi.org/10.1016/j.acra.2020.04.012

@article{b636500a1dfd48578fe132b7d597873a,

title = "Yttrium-90 Radioembolization and Tumor Hypoxia: Gas-challenge BOLD Imaging in the VX2 Rabbit Model of Hepatocellular Carcinoma",

abstract = "Rationale and Objectives: To use a rapid gas-challenge blood oxygen-level dependent magnetic resonance imaging exam to evaluate changes in tumor hypoxia after 90Y radioembolization (Y90) in the VX2 rabbit model. Materials and Methods: White New Zealand rabbits (n = 11) provided a Y90 group (n = 6 rabbits) and untreated control group (n = 5 rabbits). R2* maps were generated with gas-challenges (O2/room air) at baseline, 1 week, and 2 weeks post-Y90. Laboratory toxicity was evaluated at baseline, 24 hours, 72 hours, 1 hours, and 2 weeks. Histology was used to evaluate tumor necrosis on hematoxylin and eosin and immunofluorescence imaging was used to assess microvessel density (CD31) and proliferative index (Ki67). Results: At baseline, median tumor volumes and time to imaging were similar between groups (p = 1.000 and p = 0.4512, respectively). The median administered dose was 50.4 Gy (95% confidence interval:44.8–55.9). At week 2, mean tumor volumes were 5769.8 versus 643.7 mm3 for control versus Y90 rabbits, respectively (p = 0.0246). At two weeks, ΔR2* increased for control tumors to 12.37 ± 12.36sec−1 and decreased to 4.48 ± 9.00sec−1 after Y90. The Pearson correlation coefficient for ΔR2* at baseline and percent increase in tumor size by two weeks was 0.798 for the Y90 group (p = 0.002). There was no difference in mean microvessel density for control versus Y90 treated tumors (p = 0.6682). The mean proliferative index was reduced in Y90 treated tumors at 30.5% versus 47.5% for controls (p = 0.0071). Conclusion: The baseline ΔR2* of tumors prior to Y90 may be a predictive imaging biomarker of tumor response and treatment of these tumors with Y90 may influence tumor oxygenation over time.",

keywords = "Hepatic radioembolization, Magnetic resonance imaging, Oxygenation, Yttrium-90",

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

note = "Publisher Copyright: {\textcopyright} 2020 The Association of University Radiologists",

year = "2021",

month = jun,

doi = "10.1016/j.acra.2020.04.012",

language = "English (US)",

volume = "28",

pages = "849--858",

journal = "Academic radiology",

issn = "1076-6332",

publisher = "Elsevier Inc.",

number = "6",

}

Gordon, AC, White, SB, Gates, VL, Procissi, D, Harris, KR, Yang, Y, Zhang, Z, Li, W, Lyu, T, Huang, X, Omary, RA, Salem, R , Lewandowski, RJ & Larson, AC 2021, 'Yttrium-90 Radioembolization and Tumor Hypoxia: Gas-challenge BOLD Imaging in the VX2 Rabbit Model of Hepatocellular Carcinoma', Academic radiology, vol. 28, no. 6, pp. 849-858. https://doi.org/10.1016/j.acra.2020.04.012

TY - JOUR

T1 - Yttrium-90 Radioembolization and Tumor Hypoxia

T2 - Gas-challenge BOLD Imaging in the VX2 Rabbit Model of Hepatocellular Carcinoma

AU - Gordon, Andrew C.

AU - White, Sarah B.

AU - Gates, Vanessa L.

AU - Procissi, Daniel

AU - Harris, Kathleen R.

AU - Yang, Yihe

AU - Zhang, Zhuoli

AU - Li, Weiguo

AU - Lyu, Tianchu

AU - Huang, Xiaoke

AU - Omary, Reed A.

AU - Salem, Riad

AU - Lewandowski, Robert J.

AU - Larson, Andrew Christian

PY - 2021/6

Y1 - 2021/6

N2 - Rationale and Objectives: To use a rapid gas-challenge blood oxygen-level dependent magnetic resonance imaging exam to evaluate changes in tumor hypoxia after 90Y radioembolization (Y90) in the VX2 rabbit model. Materials and Methods: White New Zealand rabbits (n = 11) provided a Y90 group (n = 6 rabbits) and untreated control group (n = 5 rabbits). R2* maps were generated with gas-challenges (O2/room air) at baseline, 1 week, and 2 weeks post-Y90. Laboratory toxicity was evaluated at baseline, 24 hours, 72 hours, 1 hours, and 2 weeks. Histology was used to evaluate tumor necrosis on hematoxylin and eosin and immunofluorescence imaging was used to assess microvessel density (CD31) and proliferative index (Ki67). Results: At baseline, median tumor volumes and time to imaging were similar between groups (p = 1.000 and p = 0.4512, respectively). The median administered dose was 50.4 Gy (95% confidence interval:44.8–55.9). At week 2, mean tumor volumes were 5769.8 versus 643.7 mm3 for control versus Y90 rabbits, respectively (p = 0.0246). At two weeks, ΔR2* increased for control tumors to 12.37 ± 12.36sec−1 and decreased to 4.48 ± 9.00sec−1 after Y90. The Pearson correlation coefficient for ΔR2* at baseline and percent increase in tumor size by two weeks was 0.798 for the Y90 group (p = 0.002). There was no difference in mean microvessel density for control versus Y90 treated tumors (p = 0.6682). The mean proliferative index was reduced in Y90 treated tumors at 30.5% versus 47.5% for controls (p = 0.0071). Conclusion: The baseline ΔR2* of tumors prior to Y90 may be a predictive imaging biomarker of tumor response and treatment of these tumors with Y90 may influence tumor oxygenation over time.

AB - Rationale and Objectives: To use a rapid gas-challenge blood oxygen-level dependent magnetic resonance imaging exam to evaluate changes in tumor hypoxia after 90Y radioembolization (Y90) in the VX2 rabbit model. Materials and Methods: White New Zealand rabbits (n = 11) provided a Y90 group (n = 6 rabbits) and untreated control group (n = 5 rabbits). R2* maps were generated with gas-challenges (O2/room air) at baseline, 1 week, and 2 weeks post-Y90. Laboratory toxicity was evaluated at baseline, 24 hours, 72 hours, 1 hours, and 2 weeks. Histology was used to evaluate tumor necrosis on hematoxylin and eosin and immunofluorescence imaging was used to assess microvessel density (CD31) and proliferative index (Ki67). Results: At baseline, median tumor volumes and time to imaging were similar between groups (p = 1.000 and p = 0.4512, respectively). The median administered dose was 50.4 Gy (95% confidence interval:44.8–55.9). At week 2, mean tumor volumes were 5769.8 versus 643.7 mm3 for control versus Y90 rabbits, respectively (p = 0.0246). At two weeks, ΔR2* increased for control tumors to 12.37 ± 12.36sec−1 and decreased to 4.48 ± 9.00sec−1 after Y90. The Pearson correlation coefficient for ΔR2* at baseline and percent increase in tumor size by two weeks was 0.798 for the Y90 group (p = 0.002). There was no difference in mean microvessel density for control versus Y90 treated tumors (p = 0.6682). The mean proliferative index was reduced in Y90 treated tumors at 30.5% versus 47.5% for controls (p = 0.0071). Conclusion: The baseline ΔR2* of tumors prior to Y90 may be a predictive imaging biomarker of tumor response and treatment of these tumors with Y90 may influence tumor oxygenation over time.

KW - Hepatic radioembolization

KW - Magnetic resonance imaging

KW - Oxygenation

KW - Yttrium-90

UR - http://www.scopus.com/inward/record.url?scp=85086017926&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85086017926&partnerID=8YFLogxK

U2 - 10.1016/j.acra.2020.04.012

DO - 10.1016/j.acra.2020.04.012

M3 - Article

C2 - 32522403

AN - SCOPUS:85086017926

SN - 1076-6332

VL - 28

SP - 849

EP - 858

JO - Academic radiology

JF - Academic radiology

IS - 6

ER -

Yttrium-90 Radioembolization and Tumor Hypoxia: Gas-challenge BOLD Imaging in the VX2 Rabbit Model of Hepatocellular Carcinoma

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this