[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 languageEnglish
Article number44
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging Research
Volume13
Issue number1
DOIs
Publication statusPublished - 17 May 2023

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