[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 n...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SpringerOpen
2023-05-01
|
| Series: | EJNMMI Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13550-023-00990-7 |
| _version_ | 1797822702424162304 |
|---|---|
| author | Muhummad Sohaib Nazir Daniel Johnathan Hughes Gitasha Chand Kathryn Adamson Jessica Johnson Damion Bailey Victoria Gibson Hong Hoi Ting Alexander R. Lyon Gary J. R. Cook PECan study group |
| author_facet | Muhummad Sohaib Nazir Daniel Johnathan Hughes Gitasha Chand Kathryn Adamson Jessica Johnson Damion Bailey Victoria Gibson Hong Hoi Ting Alexander R. Lyon Gary J. R. Cook PECan study group |
| author_sort | Muhummad Sohaib Nazir |
| collection | DOAJ |
| description | 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 (LVmax:BP) and (RVmax:BP) were measured. LVmax was compared to background skeletal muscle (musclemax). Intra-rater reliability was determined by intraclass correlation coefficient (ICC) and Bland–Altman analysis. Results Mean LVmax:BP values were 2.76 ± 0.67 at baseline vs 2.55 ± 0.77 at 9 weeks (p = 0.42). Mean RVmax: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 (LVmax to musclemax 3.71 ± 0.77 vs 0.98 ± 0.20 (p < 0.001)) and at least twofold for the RV (LVmax to musclemax 2.49 ± 0.63 vs 0.98 ± 0.20 (p < 0.001)). There was excellent intra-rater reliability for LVmax: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. |
| first_indexed | 2024-03-13T10:13:02Z |
| format | Article |
| id | doaj.art-e4af95089d944a31b4f9fa21c1721e41 |
| institution | Directory Open Access Journal |
| issn | 2191-219X |
| language | English |
| last_indexed | 2024-03-13T10:13:02Z |
| publishDate | 2023-05-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | EJNMMI Research |
| spelling | doaj.art-e4af95089d944a31b4f9fa21c1721e412023-05-21T11:27:10ZengSpringerOpenEJNMMI Research2191-219X2023-05-011311810.1186/s13550-023-00990-7[99mTc]-labelled anti-Programmed Death-Ligand 1 single-domain antibody SPECT/CT: a novel imaging biomarker for myocardial PD-L1 expressionMuhummad Sohaib Nazir0Daniel Johnathan Hughes1Gitasha Chand2Kathryn Adamson3Jessica Johnson4Damion Bailey5Victoria Gibson6Hong Hoi Ting7Alexander R. Lyon8Gary J. R. Cook9PECan study groupDepartment of Cardiovascular Imaging, School of Biomedical Engineering and Imaging Sciences, King’s College LondonDepartment of Cancer Imaging, School of Biomedical Engineering and Imaging Sciences, King’s College LondonDepartment of Cancer Imaging, School of Biomedical Engineering and Imaging Sciences, King’s College LondonDepartment of Nuclear Medicine, Guy’s and St Thomas’ NHS Foundation TrustDepartment of Nuclear Medicine, Guy’s and St Thomas’ NHS Foundation TrustDepartment of Nuclear Medicine, Guy’s and St Thomas’ NHS Foundation TrustDepartment of Nuclear Medicine, Guy’s and St Thomas’ NHS Foundation TrustNanomab Technology (UK) LimitedRoyal Brompton Hospital, Guy’s and St Thomas’ NHS Foundation TrustDepartment of Cancer Imaging, School of Biomedical Engineering and Imaging Sciences, King’s College LondonAbstract 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 (LVmax:BP) and (RVmax:BP) were measured. LVmax was compared to background skeletal muscle (musclemax). Intra-rater reliability was determined by intraclass correlation coefficient (ICC) and Bland–Altman analysis. Results Mean LVmax:BP values were 2.76 ± 0.67 at baseline vs 2.55 ± 0.77 at 9 weeks (p = 0.42). Mean RVmax: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 (LVmax to musclemax 3.71 ± 0.77 vs 0.98 ± 0.20 (p < 0.001)) and at least twofold for the RV (LVmax to musclemax 2.49 ± 0.63 vs 0.98 ± 0.20 (p < 0.001)). There was excellent intra-rater reliability for LVmax: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.https://doi.org/10.1186/s13550-023-00990-7SPECT-CTImmune checkpoint inhibitorPD-L1 expression |
| spellingShingle | Muhummad Sohaib Nazir Daniel Johnathan Hughes Gitasha Chand Kathryn Adamson Jessica Johnson Damion Bailey Victoria Gibson Hong Hoi Ting Alexander R. Lyon Gary J. R. Cook PECan study group [99mTc]-labelled anti-Programmed Death-Ligand 1 single-domain antibody SPECT/CT: a novel imaging biomarker for myocardial PD-L1 expression EJNMMI Research SPECT-CT Immune checkpoint inhibitor PD-L1 expression |
| title | [99mTc]-labelled anti-Programmed Death-Ligand 1 single-domain antibody SPECT/CT: a novel imaging biomarker for myocardial PD-L1 expression |
| title_full | [99mTc]-labelled anti-Programmed Death-Ligand 1 single-domain antibody SPECT/CT: a novel imaging biomarker for myocardial PD-L1 expression |
| title_fullStr | [99mTc]-labelled anti-Programmed Death-Ligand 1 single-domain antibody SPECT/CT: a novel imaging biomarker for myocardial PD-L1 expression |
| title_full_unstemmed | [99mTc]-labelled anti-Programmed Death-Ligand 1 single-domain antibody SPECT/CT: a novel imaging biomarker for myocardial PD-L1 expression |
| title_short | [99mTc]-labelled anti-Programmed Death-Ligand 1 single-domain antibody SPECT/CT: a novel imaging biomarker for myocardial PD-L1 expression |
| title_sort | 99mtc labelled anti programmed death ligand 1 single domain antibody spect ct a novel imaging biomarker for myocardial pd l1 expression |
| topic | SPECT-CT Immune checkpoint inhibitor PD-L1 expression |
| url | https://doi.org/10.1186/s13550-023-00990-7 |
| work_keys_str_mv | AT muhummadsohaibnazir 99mtclabelledantiprogrammeddeathligand1singledomainantibodyspectctanovelimagingbiomarkerformyocardialpdl1expression AT danieljohnathanhughes 99mtclabelledantiprogrammeddeathligand1singledomainantibodyspectctanovelimagingbiomarkerformyocardialpdl1expression AT gitashachand 99mtclabelledantiprogrammeddeathligand1singledomainantibodyspectctanovelimagingbiomarkerformyocardialpdl1expression AT kathrynadamson 99mtclabelledantiprogrammeddeathligand1singledomainantibodyspectctanovelimagingbiomarkerformyocardialpdl1expression AT jessicajohnson 99mtclabelledantiprogrammeddeathligand1singledomainantibodyspectctanovelimagingbiomarkerformyocardialpdl1expression AT damionbailey 99mtclabelledantiprogrammeddeathligand1singledomainantibodyspectctanovelimagingbiomarkerformyocardialpdl1expression AT victoriagibson 99mtclabelledantiprogrammeddeathligand1singledomainantibodyspectctanovelimagingbiomarkerformyocardialpdl1expression AT honghoiting 99mtclabelledantiprogrammeddeathligand1singledomainantibodyspectctanovelimagingbiomarkerformyocardialpdl1expression AT alexanderrlyon 99mtclabelledantiprogrammeddeathligand1singledomainantibodyspectctanovelimagingbiomarkerformyocardialpdl1expression AT garyjrcook 99mtclabelledantiprogrammeddeathligand1singledomainantibodyspectctanovelimagingbiomarkerformyocardialpdl1expression AT pecanstudygroup 99mtclabelledantiprogrammeddeathligand1singledomainantibodyspectctanovelimagingbiomarkerformyocardialpdl1expression |