Inter-rater and intra-rater agreement of [
            99mTc]-labelled NM-01, a single-domain programmed death-ligand 1 (PD-L1) antibody, using quantitative SPECT/CT in non-small cell lung cancer

Daniel Hughes; Gitasha Chand; Jessica Johnson; Damion Bailey; Kathryn Adamson; Vicky Goh; Gary Cook

doi:doi: 10.1186/s13550-023-01002-4

Inter-rater and intra-rater agreement of [ ^99mTc]-labelled NM-01, a single-domain programmed death-ligand 1 (PD-L1) antibody, using quantitative SPECT/CT in non-small cell lung cancer

Daniel Hughes, Gitasha Chand, Jessica Johnson, Damion Bailey, Kathryn Adamson, Vicky Goh, Gary Cook

Cancer Imaging

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

Abstract

Background: Immune checkpoint inhibitors, including those against programmed cell death protein-1 (PD-1) or its ligand (PD-L1), are routinely used to treat non-small cell lung cancer (NSCLC). PD-L1 is a validated prognostic and predictive immunohistochemical biomarker of anti-PD-1/PD-L1 therapy but displays temporospatial heterogeneity of expression. Non-invasive radiopharmaceutical techniques, including technetium-99m [ ^99mTc]-labelled anti-PD-L1 single-domain antibody (NM-01) SPECT/CT, have the potential to improve the predictive value of PD-L1 assessment. This study aims to determine the inter- and intra-rater agreement of the quantitative measurement of [ ^99mTc]NM-01 SPECT/CT in NSCLC. Methods: Participants (n = 14) with untreated advanced NSCLC underwent [ ^99mTc]NM-01 SPECT/CT at baseline (n = 3) or at baseline plus 9-week follow-up (n = 11). [ ^99mTc]NM-01 uptake (of primary lung, lymph node, thoracic and distant metastases, and healthy reference tissues) was measured using SUV _max and malignant lesion-to-blood pool ratios with Siemens xSPECT Broad Quantification software by three independent raters. Intraclass correlation coefficients (ICC) were calculated and Bland–Altman plot analysis performed to determine inter- and intra-rater agreement. Results: There was excellent inter-rater agreement of manual freehand SUV _max scores of primary lung tumour (T; n = 25; ICC 1.00; 95% CI 0.99–1.00), individual lymph node metastases (LN; n = 56; ICC 0.97; 95% CI 0.95–0.98), thoracic metastases (ThMet; n = 9; ICC 0.94; 95% CI 0.83–0.99) and distant metastases (DisMet; n = 21; ICC 0.91; 95% CI 0.83–0.96). The inter-rater ICCs of tumour-to-blood pool (T:BP), LN:BP, ThMet:BP and DisMet:BP measures of [ ^99mTc]NM-01 uptake also demonstrated good or excellent agreement. Manual freehand scoring of T, LN, ThMet, DisMet and their ratios using [ ^99mTc]NM-01 SPECT/CT following a 28-day interval was consistent for all raters with good or excellent intra-rater agreement demonstrated (ICCs range 0.86–1.00). Conclusion: Quantitative assessment of [ ^99mTc]NM-01 SPECT/CT in NSCLC, using SUV _max of malignant primary or metastatic lesions and their ratios with healthy reference tissues, demonstrated good or excellent inter- and intra-rater agreement in this study. Further validation with ongoing and future larger cohort studies is now warranted. Clinical trial registration: ClinicalTrials.gov identifier no. NCT04436406 (registered 18th June 2020; available at https://clinicaltrials.gov/ct2/show/NCT04436406) and NCT04992715 (registered 5th August 2021; available at https://clinicaltrials.gov/ct2/show/NCT04992715).

Original language	English
Article number	51
Journal	European Journal of Nuclear Medicine and Molecular Imaging Research
Volume	13
Issue number	1
DOIs	https://doi.org/doi: 10.1186/s13550-023-01002-4
Publication status	Published - 28 May 2023

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doi: 10.1186/s13550-023-01002-4Licence: CC BY

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Hughes, D., Chand, G., Johnson, J., Bailey, D., Adamson, K., Goh, V., & Cook, G. (2023). Inter-rater and intra-rater agreement of [ ^99mTc]-labelled NM-01, a single-domain programmed death-ligand 1 (PD-L1) antibody, using quantitative SPECT/CT in non-small cell lung cancer. European Journal of Nuclear Medicine and Molecular Imaging Research, 13(1), [51]. https://doi.org/doi: 10.1186/s13550-023-01002-4

@article{393d8baa93ad4bb9add43e0e7359918a,

title = "Inter-rater and intra-rater agreement of [ 99mTc]-labelled NM-01, a single-domain programmed death-ligand 1 (PD-L1) antibody, using quantitative SPECT/CT in non-small cell lung cancer",

abstract = "Background: Immune checkpoint inhibitors, including those against programmed cell death protein-1 (PD-1) or its ligand (PD-L1), are routinely used to treat non-small cell lung cancer (NSCLC). PD-L1 is a validated prognostic and predictive immunohistochemical biomarker of anti-PD-1/PD-L1 therapy but displays temporospatial heterogeneity of expression. Non-invasive radiopharmaceutical techniques, including technetium-99m [ 99mTc]-labelled anti-PD-L1 single-domain antibody (NM-01) SPECT/CT, have the potential to improve the predictive value of PD-L1 assessment. This study aims to determine the inter- and intra-rater agreement of the quantitative measurement of [ 99mTc]NM-01 SPECT/CT in NSCLC. Methods: Participants (n = 14) with untreated advanced NSCLC underwent [ 99mTc]NM-01 SPECT/CT at baseline (n = 3) or at baseline plus 9-week follow-up (n = 11). [ 99mTc]NM-01 uptake (of primary lung, lymph node, thoracic and distant metastases, and healthy reference tissues) was measured using SUV max and malignant lesion-to-blood pool ratios with Siemens xSPECT Broad Quantification software by three independent raters. Intraclass correlation coefficients (ICC) were calculated and Bland–Altman plot analysis performed to determine inter- and intra-rater agreement. Results: There was excellent inter-rater agreement of manual freehand SUV max scores of primary lung tumour (T; n = 25; ICC 1.00; 95% CI 0.99–1.00), individual lymph node metastases (LN; n = 56; ICC 0.97; 95% CI 0.95–0.98), thoracic metastases (ThMet; n = 9; ICC 0.94; 95% CI 0.83–0.99) and distant metastases (DisMet; n = 21; ICC 0.91; 95% CI 0.83–0.96). The inter-rater ICCs of tumour-to-blood pool (T:BP), LN:BP, ThMet:BP and DisMet:BP measures of [ 99mTc]NM-01 uptake also demonstrated good or excellent agreement. Manual freehand scoring of T, LN, ThMet, DisMet and their ratios using [ 99mTc]NM-01 SPECT/CT following a 28-day interval was consistent for all raters with good or excellent intra-rater agreement demonstrated (ICCs range 0.86–1.00). Conclusion: Quantitative assessment of [ 99mTc]NM-01 SPECT/CT in NSCLC, using SUV max of malignant primary or metastatic lesions and their ratios with healthy reference tissues, demonstrated good or excellent inter- and intra-rater agreement in this study. Further validation with ongoing and future larger cohort studies is now warranted. Clinical trial registration: ClinicalTrials.gov identifier no. NCT04436406 (registered 18th June 2020; available at https://clinicaltrials.gov/ct2/show/NCT04436406) and NCT04992715 (registered 5th August 2021; available at https://clinicaltrials.gov/ct2/show/NCT04992715).",

author = "Daniel Hughes and Gitasha Chand and Jessica Johnson and Damion Bailey and Kathryn Adamson and Vicky Goh and Gary Cook",

note = "Funding Information: This research was supported by NanoMab Technology Limited, London, UK. The authors acknowledge financial support from the Cancer Research UK National Cancer Imaging Translational Accelerator (C1519/A28682), and the Wellcome/Engineering and Physical Sciences Research Council Centre for Medical Engineering at King{\textquoteright}s College London (WT 203148/Z/16/Z). For the purpose of open access, authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. Funding Information: DJH has received honoraria/speaker fees from Pfizer, travel/accommodation grants from Bristol-Myers Squibb, Roche and NanoMab Technology, research funding via institute from NanoMab Technology, and is an executive committee member of the Association of Cancer Physicians (UK). GCh is a director and shareholder of NanoMab Technology (UK) Ltd. GJRC has research support via institute from NanoMab Technology, Theragnostics, Serac Healthcare and provides consultancy for GE Healthcare, NanoMab Technology, Amgen and Full-Life Technologies. All other authors report no competing interests. Funding Information: The authors would like to thank all the participants involved in this study. Additionally, the authors acknowledge colleagues at King{\textquoteright}s College London, Guy{\textquoteright}s and St Thomas{\textquoteright} PET Centre and the Cancer Centre at Guy{\textquoteright}s, London, UK, for their contributions. Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = may,

day = "28",

doi = "doi: 10.1186/s13550-023-01002-4",

language = "English",

volume = "13",

journal = "European Journal of Nuclear Medicine and Molecular Imaging Research",

issn = "2191-219X",

publisher = "BioMed Central",

number = "1",

}

Hughes, D, Chand, G, Johnson, J, Bailey, D, Adamson, K, Goh, V & Cook, G 2023, 'Inter-rater and intra-rater agreement of [ ^99mTc]-labelled NM-01, a single-domain programmed death-ligand 1 (PD-L1) antibody, using quantitative SPECT/CT in non-small cell lung cancer', European Journal of Nuclear Medicine and Molecular Imaging Research, vol. 13, no. 1, 51. https://doi.org/doi: 10.1186/s13550-023-01002-4

Inter-rater and intra-rater agreement of [ ^99mTc]-labelled NM-01, a single-domain programmed death-ligand 1 (PD-L1) antibody, using quantitative SPECT/CT in non-small cell lung cancer. / Hughes, Daniel; Chand, Gitasha; Johnson, Jessica et al.
In: European Journal of Nuclear Medicine and Molecular Imaging Research, Vol. 13, No. 1, 51, 28.05.2023.

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

TY - JOUR

T1 - Inter-rater and intra-rater agreement of [ 99mTc]-labelled NM-01, a single-domain programmed death-ligand 1 (PD-L1) antibody, using quantitative SPECT/CT in non-small cell lung cancer

AU - Hughes, Daniel

AU - Chand, Gitasha

AU - Johnson, Jessica

AU - Bailey, Damion

AU - Adamson, Kathryn

AU - Goh, Vicky

AU - Cook, Gary

N1 - Funding Information: This research was supported by NanoMab Technology Limited, London, UK. The authors acknowledge financial support from the Cancer Research UK National Cancer Imaging Translational Accelerator (C1519/A28682), and the Wellcome/Engineering and Physical Sciences Research Council Centre for Medical Engineering at King’s College London (WT 203148/Z/16/Z). For the purpose of open access, authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. Funding Information: DJH has received honoraria/speaker fees from Pfizer, travel/accommodation grants from Bristol-Myers Squibb, Roche and NanoMab Technology, research funding via institute from NanoMab Technology, and is an executive committee member of the Association of Cancer Physicians (UK). GCh is a director and shareholder of NanoMab Technology (UK) Ltd. GJRC has research support via institute from NanoMab Technology, Theragnostics, Serac Healthcare and provides consultancy for GE Healthcare, NanoMab Technology, Amgen and Full-Life Technologies. All other authors report no competing interests. Funding Information: The authors would like to thank all the participants involved in this study. Additionally, the authors acknowledge colleagues at King’s College London, Guy’s and St Thomas’ PET Centre and the Cancer Centre at Guy’s, London, UK, for their contributions. Publisher Copyright: © 2023, The Author(s).

PY - 2023/5/28

Y1 - 2023/5/28

N2 - Background: Immune checkpoint inhibitors, including those against programmed cell death protein-1 (PD-1) or its ligand (PD-L1), are routinely used to treat non-small cell lung cancer (NSCLC). PD-L1 is a validated prognostic and predictive immunohistochemical biomarker of anti-PD-1/PD-L1 therapy but displays temporospatial heterogeneity of expression. Non-invasive radiopharmaceutical techniques, including technetium-99m [ 99mTc]-labelled anti-PD-L1 single-domain antibody (NM-01) SPECT/CT, have the potential to improve the predictive value of PD-L1 assessment. This study aims to determine the inter- and intra-rater agreement of the quantitative measurement of [ 99mTc]NM-01 SPECT/CT in NSCLC. Methods: Participants (n = 14) with untreated advanced NSCLC underwent [ 99mTc]NM-01 SPECT/CT at baseline (n = 3) or at baseline plus 9-week follow-up (n = 11). [ 99mTc]NM-01 uptake (of primary lung, lymph node, thoracic and distant metastases, and healthy reference tissues) was measured using SUV max and malignant lesion-to-blood pool ratios with Siemens xSPECT Broad Quantification software by three independent raters. Intraclass correlation coefficients (ICC) were calculated and Bland–Altman plot analysis performed to determine inter- and intra-rater agreement. Results: There was excellent inter-rater agreement of manual freehand SUV max scores of primary lung tumour (T; n = 25; ICC 1.00; 95% CI 0.99–1.00), individual lymph node metastases (LN; n = 56; ICC 0.97; 95% CI 0.95–0.98), thoracic metastases (ThMet; n = 9; ICC 0.94; 95% CI 0.83–0.99) and distant metastases (DisMet; n = 21; ICC 0.91; 95% CI 0.83–0.96). The inter-rater ICCs of tumour-to-blood pool (T:BP), LN:BP, ThMet:BP and DisMet:BP measures of [ 99mTc]NM-01 uptake also demonstrated good or excellent agreement. Manual freehand scoring of T, LN, ThMet, DisMet and their ratios using [ 99mTc]NM-01 SPECT/CT following a 28-day interval was consistent for all raters with good or excellent intra-rater agreement demonstrated (ICCs range 0.86–1.00). Conclusion: Quantitative assessment of [ 99mTc]NM-01 SPECT/CT in NSCLC, using SUV max of malignant primary or metastatic lesions and their ratios with healthy reference tissues, demonstrated good or excellent inter- and intra-rater agreement in this study. Further validation with ongoing and future larger cohort studies is now warranted. Clinical trial registration: ClinicalTrials.gov identifier no. NCT04436406 (registered 18th June 2020; available at https://clinicaltrials.gov/ct2/show/NCT04436406) and NCT04992715 (registered 5th August 2021; available at https://clinicaltrials.gov/ct2/show/NCT04992715).

AB - Background: Immune checkpoint inhibitors, including those against programmed cell death protein-1 (PD-1) or its ligand (PD-L1), are routinely used to treat non-small cell lung cancer (NSCLC). PD-L1 is a validated prognostic and predictive immunohistochemical biomarker of anti-PD-1/PD-L1 therapy but displays temporospatial heterogeneity of expression. Non-invasive radiopharmaceutical techniques, including technetium-99m [ 99mTc]-labelled anti-PD-L1 single-domain antibody (NM-01) SPECT/CT, have the potential to improve the predictive value of PD-L1 assessment. This study aims to determine the inter- and intra-rater agreement of the quantitative measurement of [ 99mTc]NM-01 SPECT/CT in NSCLC. Methods: Participants (n = 14) with untreated advanced NSCLC underwent [ 99mTc]NM-01 SPECT/CT at baseline (n = 3) or at baseline plus 9-week follow-up (n = 11). [ 99mTc]NM-01 uptake (of primary lung, lymph node, thoracic and distant metastases, and healthy reference tissues) was measured using SUV max and malignant lesion-to-blood pool ratios with Siemens xSPECT Broad Quantification software by three independent raters. Intraclass correlation coefficients (ICC) were calculated and Bland–Altman plot analysis performed to determine inter- and intra-rater agreement. Results: There was excellent inter-rater agreement of manual freehand SUV max scores of primary lung tumour (T; n = 25; ICC 1.00; 95% CI 0.99–1.00), individual lymph node metastases (LN; n = 56; ICC 0.97; 95% CI 0.95–0.98), thoracic metastases (ThMet; n = 9; ICC 0.94; 95% CI 0.83–0.99) and distant metastases (DisMet; n = 21; ICC 0.91; 95% CI 0.83–0.96). The inter-rater ICCs of tumour-to-blood pool (T:BP), LN:BP, ThMet:BP and DisMet:BP measures of [ 99mTc]NM-01 uptake also demonstrated good or excellent agreement. Manual freehand scoring of T, LN, ThMet, DisMet and their ratios using [ 99mTc]NM-01 SPECT/CT following a 28-day interval was consistent for all raters with good or excellent intra-rater agreement demonstrated (ICCs range 0.86–1.00). Conclusion: Quantitative assessment of [ 99mTc]NM-01 SPECT/CT in NSCLC, using SUV max of malignant primary or metastatic lesions and their ratios with healthy reference tissues, demonstrated good or excellent inter- and intra-rater agreement in this study. Further validation with ongoing and future larger cohort studies is now warranted. Clinical trial registration: ClinicalTrials.gov identifier no. NCT04436406 (registered 18th June 2020; available at https://clinicaltrials.gov/ct2/show/NCT04436406) and NCT04992715 (registered 5th August 2021; available at https://clinicaltrials.gov/ct2/show/NCT04992715).

UR - http://www.scopus.com/inward/record.url?scp=85160642816&partnerID=8YFLogxK

U2 - doi: 10.1186/s13550-023-01002-4

DO - doi: 10.1186/s13550-023-01002-4

M3 - Article

SN - 2191-219X

VL - 13

JO - European Journal of Nuclear Medicine and Molecular Imaging Research

JF - European Journal of Nuclear Medicine and Molecular Imaging Research

IS - 1

M1 - 51

ER -

Hughes D, Chand G, Johnson J, Bailey D, Adamson K, Goh V et al. Inter-rater and intra-rater agreement of [ ^99mTc]-labelled NM-01, a single-domain programmed death-ligand 1 (PD-L1) antibody, using quantitative SPECT/CT in non-small cell lung cancer. European Journal of Nuclear Medicine and Molecular Imaging Research. 2023 May 28;13(1):51. doi: doi: 10.1186/s13550-023-01002-4

Inter-rater and intra-rater agreement of [ ^99mTc]-labelled NM-01, a single-domain programmed death-ligand 1 (PD-L1) antibody, using quantitative SPECT/CT in non-small cell lung cancer

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