[99mTc]-labelled anti-Programmed Death-Ligand 1 single-domain antibody SPECT/CT: a novel imaging biomarker for myocardial PD-L1 expression

Muhummad Nazir; Daniel Hughes; Gitasha Chand; Kathryn Adamson; Jessica Johnson; Damion Bailey; Victoria Gibson; Hong Hoi Ting; Alexander R  Lyon; Gary Cook; null PECan Study Group

doi:10.1186/s13550-023-00990-7

[^99mTc]-labelled anti-Programmed Death-Ligand 1 single-domain antibody SPECT/CT: a novel imaging biomarker for myocardial PD-L1 expression

Muhummad Nazir^*, Daniel Hughes, Gitasha Chand, Kathryn Adamson, Jessica Johnson, Damion Bailey, Victoria Gibson, Hong Hoi Ting, Alexander R Lyon, Gary Cook, PECan Study Group

^*Corresponding author for this work

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Abstract

Background: Myocardial programmed death-ligand 1 (PD-L1) expression is implicated in immune checkpoint inhibitor (ICI)-associated myocarditis. Measurement of myocardial PD-L1 expression may have potential use as a mechanistic and predictive biomarker. The aim of this study was to determine non-invasive assessment of myocardial PD-L1 expression using [ ^99mTc]-labelled anti-PD-L1 single-domain antibody (NM-01) SPECT/CT. Methods: Thoracic [ ^99mTc]NM-01 SPECT/CT was performed in lung cancer patients (n = 10) at baseline and 9-weeks following anti-programmed cell death protein 1 (PD-1) therapy. Baseline and 9-week left ventricular and right ventricular to blood pool ratios (LV _max:BP) and (RV _max:BP) were measured. LV _max was compared to background skeletal muscle (muscle _max). Intra-rater reliability was determined by intraclass correlation coefficient (ICC) and Bland–Altman analysis. Results: Mean LV _max:BP values were 2.76 ± 0.67 at baseline vs 2.55 ± 0.77 at 9 weeks (p = 0.42). Mean RV _max:BP was 1.82 ± 0.32 at baseline vs 1.76 ± 0.45 at 9 weeks (p = 0.67). Myocardial PD-L1 expression was at least threefold greater than skeletal muscle at baseline for the LV (LV _max to muscle _max 3.71 ± 0.77 vs 0.98 ± 0.20 (p < 0.001)) and at least twofold for the RV (LV _max to muscle _max 2.49 ± 0.63 vs 0.98 ± 0.20 (p < 0.001)). There was excellent intra-rater reliability for LV _max:BP with ICC 0.99 (95% confidence interval 0.94–0.99, p < 0.001), mean bias -0.05 ± 0.14 (95% limits of agreement -0.32 to 0.21). There were no major adverse cardiovascular events or myocarditis during follow-up. Conclusion: This study is the first to report PD-L1 expression of the heart that can be quantified non-invasively without invasive myocardial biopsy, with high reliability and specificity. This technique can be applied to investigate myocardial PD-L1 expression in ICI-associated myocarditis and cardiomyopathies. Clinical trial registration PD-L1 Expression in Cancer (PECan) study (NCT04436406). https://clinicaltrials.gov/ct2/show/NCT04436406 June 18th, 2020.

Original language	English
Article number	44
Journal	European Journal of Nuclear Medicine and Molecular Imaging Research
Volume	13
Issue number	1
DOIs	https://doi.org/10.1186/s13550-023-00990-7
Publication status	Published - 17 May 2023

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10.1186/s13550-023-00990-7

[ 99mTc]-labelled anti-Programmed Death-Ligand 1 single-domain antibody SPECT/ CT: a novel imaging biomarker for myocardial PD-L1 expressionFinal published version, 1 MBLicence: CC BY

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Nazir, M., Hughes, D., Chand, G., Adamson, K., Johnson, J., Bailey, D., Gibson, V., Ting, H. H., Lyon, A. R., Cook, G., & PECan Study Group (2023). [^99mTc]-labelled anti-Programmed Death-Ligand 1 single-domain antibody SPECT/CT: a novel imaging biomarker for myocardial PD-L1 expression. European Journal of Nuclear Medicine and Molecular Imaging Research, 13(1), [44]. https://doi.org/10.1186/s13550-023-00990-7

@article{9c59e93259044f1f98b826181b6152a0,

title = "[99mTc]-labelled anti-Programmed Death-Ligand 1 single-domain antibody SPECT/CT: a novel imaging biomarker for myocardial PD-L1 expression",

abstract = "Background: Myocardial programmed death-ligand 1 (PD-L1) expression is implicated in immune checkpoint inhibitor (ICI)-associated myocarditis. Measurement of myocardial PD-L1 expression may have potential use as a mechanistic and predictive biomarker. The aim of this study was to determine non-invasive assessment of myocardial PD-L1 expression using [ 99mTc]-labelled anti-PD-L1 single-domain antibody (NM-01) SPECT/CT. Methods: Thoracic [ 99mTc]NM-01 SPECT/CT was performed in lung cancer patients (n = 10) at baseline and 9-weeks following anti-programmed cell death protein 1 (PD-1) therapy. Baseline and 9-week left ventricular and right ventricular to blood pool ratios (LV max:BP) and (RV max:BP) were measured. LV max was compared to background skeletal muscle (muscle max). Intra-rater reliability was determined by intraclass correlation coefficient (ICC) and Bland–Altman analysis. Results: Mean LV max:BP values were 2.76 ± 0.67 at baseline vs 2.55 ± 0.77 at 9 weeks (p = 0.42). Mean RV max:BP was 1.82 ± 0.32 at baseline vs 1.76 ± 0.45 at 9 weeks (p = 0.67). Myocardial PD-L1 expression was at least threefold greater than skeletal muscle at baseline for the LV (LV max to muscle max 3.71 ± 0.77 vs 0.98 ± 0.20 (p < 0.001)) and at least twofold for the RV (LV max to muscle max 2.49 ± 0.63 vs 0.98 ± 0.20 (p < 0.001)). There was excellent intra-rater reliability for LV max:BP with ICC 0.99 (95% confidence interval 0.94–0.99, p < 0.001), mean bias -0.05 ± 0.14 (95% limits of agreement -0.32 to 0.21). There were no major adverse cardiovascular events or myocarditis during follow-up. Conclusion: This study is the first to report PD-L1 expression of the heart that can be quantified non-invasively without invasive myocardial biopsy, with high reliability and specificity. This technique can be applied to investigate myocardial PD-L1 expression in ICI-associated myocarditis and cardiomyopathies. Clinical trial registration PD-L1 Expression in Cancer (PECan) study (NCT04436406). https://clinicaltrials.gov/ct2/show/NCT04436406 June 18th, 2020.",

author = "Muhummad Nazir and Daniel Hughes and Gitasha Chand and Kathryn Adamson and Jessica Johnson and Damion Bailey and Victoria Gibson and Ting, {Hong Hoi} and Lyon, {Alexander R} and Gary Cook and {PECan Study Group}",

note = "Funding Information: The authors acknowledge financial support from the Department of Health through the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy{\textquoteright}s & St Thomas{\textquoteright} NHS Foundation Trust in partnership with King{\textquoteright}s College London and King{\textquoteright}s College Hospital NHS Foundation Trust and by the NIHR MedTech Co-operative for Cardiovascular Disease at Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust. This work was funded by Nanomab Technology (UK) Limited. This work was also supported by the Wellcome/EPSRC Centre for Medical Engineering [WT 203148/Z/16/Z]. MSN was funded by a NIHR Clinical Lectureship [CL-2019–17-001]. ARL is supported by the Fondation Leducq Network of Excellence in Cardio-Oncology. The views expressed are those of the authors and not necessarily those of the BHF, the DoH, the EPSRC, the NHS, the NIHR, or the Wellcome Trust. Funding Information: The authors would like to acknowledge the PECan study group: Scott Edmonds, Department of Nuclear Medicine, Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust, London, UK scott.edmonds@gstt.nhs.uk; Alexandros Georgiou, King{\textquoteright}s Health Partners Comprehensive Cancer Centre, Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust, London, UK alexandros.georgiou@gstt.nhs.uk; Eleni Karapanagiotou, King{\textquoteright}s Health Partners Comprehensive Cancer Centre, Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust, London, UK eleni.karapanagiotou@gstt.nhs.uk; Debra Josephs, King{\textquoteright}s Health Partners Comprehensive Cancer Centre, Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust, London, UK; School of Cancer and Pharmaceutical Sciences, King{\textquoteright}s College London, London, UK debra.josephs@gstt.nhs.uk; Emma McLean, Department of Histopathology, Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust, London, UK emma.mclean@gstt.nhs.uk; James Spicer, King{\textquoteright}s Health Partners Comprehensive Cancer Centre, Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust, London, UK; School of Cancer and Pharmaceutical Sciences, King{\textquoteright}s College London, London, UK james.spicer@kcl.ac.uk; Vicky Goh, Department of Cancer Imaging, School of Biomedical Engineering and Imaging Sciences, King{\textquoteright}s College London, London, UK vicky.goh@kcl.ac.uk. Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = may,

day = "17",

doi = "10.1186/s13550-023-00990-7",

language = "English",

volume = "13",

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

issn = "2191-219X",

publisher = "BioMed Central",

number = "1",

}

Nazir, M , Hughes, D, Chand, G, Adamson, K, Johnson, J, Bailey, D, Gibson, V, Ting, HH, Lyon, AR, Cook, G & PECan Study Group 2023, '[^99mTc]-labelled anti-Programmed Death-Ligand 1 single-domain antibody SPECT/CT: a novel imaging biomarker for myocardial PD-L1 expression', European Journal of Nuclear Medicine and Molecular Imaging Research, vol. 13, no. 1, 44. https://doi.org/10.1186/s13550-023-00990-7

TY - JOUR

T1 - [99mTc]-labelled anti-Programmed Death-Ligand 1 single-domain antibody SPECT/CT: a novel imaging biomarker for myocardial PD-L1 expression

AU - Nazir, Muhummad

AU - Hughes, Daniel

AU - Chand, Gitasha

AU - Adamson, Kathryn

AU - Johnson, Jessica

AU - Bailey, Damion

AU - Gibson, Victoria

AU - Ting, Hong Hoi

AU - Lyon, Alexander R

AU - Cook, Gary

AU - PECan Study Group, null

N1 - Funding Information: The authors acknowledge financial support from the Department of Health through the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust and by the NIHR MedTech Co-operative for Cardiovascular Disease at Guy’s and St Thomas’ NHS Foundation Trust. This work was funded by Nanomab Technology (UK) Limited. This work was also supported by the Wellcome/EPSRC Centre for Medical Engineering [WT 203148/Z/16/Z]. MSN was funded by a NIHR Clinical Lectureship [CL-2019–17-001]. ARL is supported by the Fondation Leducq Network of Excellence in Cardio-Oncology. The views expressed are those of the authors and not necessarily those of the BHF, the DoH, the EPSRC, the NHS, the NIHR, or the Wellcome Trust. Funding Information: The authors would like to acknowledge the PECan study group: Scott Edmonds, Department of Nuclear Medicine, Guy’s and St Thomas’ NHS Foundation Trust, London, UK scott.edmonds@gstt.nhs.uk; Alexandros Georgiou, King’s Health Partners Comprehensive Cancer Centre, Guy’s and St Thomas’ NHS Foundation Trust, London, UK alexandros.georgiou@gstt.nhs.uk; Eleni Karapanagiotou, King’s Health Partners Comprehensive Cancer Centre, Guy’s and St Thomas’ NHS Foundation Trust, London, UK eleni.karapanagiotou@gstt.nhs.uk; Debra Josephs, King’s Health Partners Comprehensive Cancer Centre, Guy’s and St Thomas’ NHS Foundation Trust, London, UK; School of Cancer and Pharmaceutical Sciences, King’s College London, London, UK debra.josephs@gstt.nhs.uk; Emma McLean, Department of Histopathology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK emma.mclean@gstt.nhs.uk; James Spicer, King’s Health Partners Comprehensive Cancer Centre, Guy’s and St Thomas’ NHS Foundation Trust, London, UK; School of Cancer and Pharmaceutical Sciences, King’s College London, London, UK james.spicer@kcl.ac.uk; Vicky Goh, Department of Cancer Imaging, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK vicky.goh@kcl.ac.uk. Publisher Copyright: © 2023, The Author(s).

PY - 2023/5/17

Y1 - 2023/5/17

N2 - Background: Myocardial programmed death-ligand 1 (PD-L1) expression is implicated in immune checkpoint inhibitor (ICI)-associated myocarditis. Measurement of myocardial PD-L1 expression may have potential use as a mechanistic and predictive biomarker. The aim of this study was to determine non-invasive assessment of myocardial PD-L1 expression using [ 99mTc]-labelled anti-PD-L1 single-domain antibody (NM-01) SPECT/CT. Methods: Thoracic [ 99mTc]NM-01 SPECT/CT was performed in lung cancer patients (n = 10) at baseline and 9-weeks following anti-programmed cell death protein 1 (PD-1) therapy. Baseline and 9-week left ventricular and right ventricular to blood pool ratios (LV max:BP) and (RV max:BP) were measured. LV max was compared to background skeletal muscle (muscle max). Intra-rater reliability was determined by intraclass correlation coefficient (ICC) and Bland–Altman analysis. Results: Mean LV max:BP values were 2.76 ± 0.67 at baseline vs 2.55 ± 0.77 at 9 weeks (p = 0.42). Mean RV max:BP was 1.82 ± 0.32 at baseline vs 1.76 ± 0.45 at 9 weeks (p = 0.67). Myocardial PD-L1 expression was at least threefold greater than skeletal muscle at baseline for the LV (LV max to muscle max 3.71 ± 0.77 vs 0.98 ± 0.20 (p < 0.001)) and at least twofold for the RV (LV max to muscle max 2.49 ± 0.63 vs 0.98 ± 0.20 (p < 0.001)). There was excellent intra-rater reliability for LV max:BP with ICC 0.99 (95% confidence interval 0.94–0.99, p < 0.001), mean bias -0.05 ± 0.14 (95% limits of agreement -0.32 to 0.21). There were no major adverse cardiovascular events or myocarditis during follow-up. Conclusion: This study is the first to report PD-L1 expression of the heart that can be quantified non-invasively without invasive myocardial biopsy, with high reliability and specificity. This technique can be applied to investigate myocardial PD-L1 expression in ICI-associated myocarditis and cardiomyopathies. Clinical trial registration PD-L1 Expression in Cancer (PECan) study (NCT04436406). https://clinicaltrials.gov/ct2/show/NCT04436406 June 18th, 2020.

AB - Background: Myocardial programmed death-ligand 1 (PD-L1) expression is implicated in immune checkpoint inhibitor (ICI)-associated myocarditis. Measurement of myocardial PD-L1 expression may have potential use as a mechanistic and predictive biomarker. The aim of this study was to determine non-invasive assessment of myocardial PD-L1 expression using [ 99mTc]-labelled anti-PD-L1 single-domain antibody (NM-01) SPECT/CT. Methods: Thoracic [ 99mTc]NM-01 SPECT/CT was performed in lung cancer patients (n = 10) at baseline and 9-weeks following anti-programmed cell death protein 1 (PD-1) therapy. Baseline and 9-week left ventricular and right ventricular to blood pool ratios (LV max:BP) and (RV max:BP) were measured. LV max was compared to background skeletal muscle (muscle max). Intra-rater reliability was determined by intraclass correlation coefficient (ICC) and Bland–Altman analysis. Results: Mean LV max:BP values were 2.76 ± 0.67 at baseline vs 2.55 ± 0.77 at 9 weeks (p = 0.42). Mean RV max:BP was 1.82 ± 0.32 at baseline vs 1.76 ± 0.45 at 9 weeks (p = 0.67). Myocardial PD-L1 expression was at least threefold greater than skeletal muscle at baseline for the LV (LV max to muscle max 3.71 ± 0.77 vs 0.98 ± 0.20 (p < 0.001)) and at least twofold for the RV (LV max to muscle max 2.49 ± 0.63 vs 0.98 ± 0.20 (p < 0.001)). There was excellent intra-rater reliability for LV max:BP with ICC 0.99 (95% confidence interval 0.94–0.99, p < 0.001), mean bias -0.05 ± 0.14 (95% limits of agreement -0.32 to 0.21). There were no major adverse cardiovascular events or myocarditis during follow-up. Conclusion: This study is the first to report PD-L1 expression of the heart that can be quantified non-invasively without invasive myocardial biopsy, with high reliability and specificity. This technique can be applied to investigate myocardial PD-L1 expression in ICI-associated myocarditis and cardiomyopathies. Clinical trial registration PD-L1 Expression in Cancer (PECan) study (NCT04436406). https://clinicaltrials.gov/ct2/show/NCT04436406 June 18th, 2020.

UR - http://www.scopus.com/inward/record.url?scp=85160063807&partnerID=8YFLogxK

U2 - 10.1186/s13550-023-00990-7

DO - 10.1186/s13550-023-00990-7

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 - 44

ER -

[^99mTc]-labelled anti-Programmed Death-Ligand 1 single-domain antibody SPECT/CT: a novel imaging biomarker for myocardial PD-L1 expression

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