RETRACTED ARTICLE: Inter- and intraobserver agreement of the quantitative assessment of [99mTc]-labelled anti-programmed death-ligand 1 (PD-L1) SPECT/CT in non-small cell lung cancer

Abstract

Checkpoint inhibition therapy using monoclonal antibodies against programmed cell death protein 1 (PD-1) or its ligand (PD-L1) is now standard management of non-small cell lung cancer (NSCLC). PD-L1 expression is a validated and approved prognostic and predictive biomarker for anti-PD-1/PD-L1 therapy. Technetium-99 m [^99mTc]-labelled anti-PD-L1 single-domain antibody (NM-01) SPECT/CT quantification correlates with PD-L1 expression in NSCLC, presenting an opportunity for non-invasive assessment. The aim of this study was to determine the inter- and intraobserver agreement of the quantitative assessment of [^99mTc]NM-01 SPECT/CT in NSCLC. [^99mTc]NM-01 SPECT/CT studies of 21 consecutive NSCLC participants imaged for the evaluation of PD-L1 expression were analysed. Three independent observers measured maximum counts in a tumour region of interest (ROI_max) of primary lung, metastatic lesions and normal tissue references of both 1 and 2 h post-injection (n = 42) anonymised studies using a manual technique. Intraclass correlation coefficients (ICC) were calculated, and Bland–Altman plot analysis was performed to determine inter- and intraobserver agreement. Intraclass correlation of primary lung tumour-to-blood pool (T:BP; ICC 0.83, 95% CI 0.73–0.90) and lymph node metastasis-to-blood pool (LN:BP; ICC 0.87, 0.81–0.92) measures of [^99mTc]NM-01 uptake was good to excellent between observers. Freehand ROI_max of T (ICC 0.94), LN (ICC 0.97), liver (ICC 0.97) and BP (ICC 0.90) reference tissues also demonstrated excellent interobserver agreement. ROI_max scoring of healthy lung demonstrated moderate to excellent interobserver agreement (ICC 0.84) and improved when measured consistently at the level of the aortic arch (ICC 0.89). Manual ROI_max re-scoring of T, LN, T:BP and LN:BP using [^99mTc]NM-01 SPECT/CT following a 42-day interval was consistent with excellent intraobserver agreement (ICC range 0.95–0.97). Good to excellent inter- and intraobserver agreement of the quantitative assessment of [^99mTc]NM-01 SPECT/CT in NSCLC was demonstrated in this study, including T:BP which has been shown to correlate with PD-L1 status. [^99mTc]NM-01 SPECT/CT has the potential to reliably and non-invasively assess PD-L1 expression. ClinicalTrials.gov identifier no. NCT02978196. Registered 30th November 2016.