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P1 99mTc-single domain PD-l1 antibody (NM01): a novel imaging biomarker for non-invasive myocardial PD-l1 expression
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  1. Muhummad Sohaib Nazir1,2,
  2. Daniel Hughes3,
  3. Hong Hoi Ting4,
  4. Gitasha Chand4,
  5. Damion Bailey5,
  6. Victoria Gibson5,
  7. Kathryn Adamson5,
  8. Jessica Johnson5,
  9. Alexander R Lyon2,6,
  10. Gary JR Cook3
  1. 1Department of Cardiovascular Imaging, School of Biomedical Engineering and Imaging Sciences, King’s College London, UK
  2. 2Royal Brompton Hospital, Guy’s and St Thomas Hospital NHS Trust, London, UK
  3. 3Department of Cancer Imaging, School of Biomedical Engineering and Imaging Sciences, King’s College London, UK
  4. 4NanoMab Technology Ltd, UK
  5. 5Department of Nuclear Medicine, Guy’s and St Thomas’ NHS Foundation Trust, London, UK
  6. 6National Heart and Lung Institute, Imperial College London, London, UK

Abstract

Objective Immune checkpoint inhibitors have revolutionized the care of cancer patients and involve blockade of the PD-L1 receptor. Myocardial PD-L1 expression has been implicated in mice models in myocarditis and autoimmune dilated cardiomyopathy. PD-L1 myocardial expression may have a potential role in immune checkpoint inhibitor myocarditis. We aimed to determine the non-invasive assessment of myocardial PD-L1 expression using 99mTc-single domain PD-L1 antibody (NM01) SPECT-CT.

Methods Cancer patients (n=10) underwent two SPECT-CT scans, at baseline and following 9 weeks cancer therapy. Patients were administered with a novel radiotracer, 99mTc single domain PD-L1 antibody (NM-01), prior to imaging. Baseline and 9-week left ventricular to blood pool ratios (LVmax:BP) and right ventricular to blood pool ratios (RVmax:BP) were measured. Measurements were repeated following a three-month period.

Results Myocardial PD-L1 expression was evident in all patients. Mean LVmax:BP values were 2.9±0.63 at baseline vs 2.60±0.82 at 9-week, (p=0.37). Mean RVmax:BP were 1.74±0.28 at baseline vs 1.68±0.51 at 9-week, (p=0.71). There was excellent reliability of measurements with intraclass correlation coefficient of 0.99 (95% confidence interval 0.94–0.99, p<0.001). The mean bias of measurements was 0.08±0.23 with 95% limits of agreement -0.38 to 0.54. There were no major adverse cardiovascular events or myocarditis during follow up.

Conclusion We demonstrate the first in man study for a novel quantitative imaging biomarker for the assessment of PD-L1 expression of the heart. This finding will now facilitate future studies to allow us to determine the role of PD-L1 in a range of cardiac disease such as myocarditis and cardiomyopathies.

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