Article Text
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.