PD-L1 imaging with [99mTc]NM-01 SPECT/CT is associated with metabolic response to pembrolizumab with/without chemotherapy in advanced lung cancer
Menée sur 15 patients atteints d'un cancer du poumon non à petites cellules de stade avancé (âge médian : 63 ans ; 9 hommes), cette étude évalue la relation entre les résultats d'une tomographie numérique par émission monophotonique utilisant un anticorps anti-PD-L1 marqué au technétium 99m et la réponse métabolique au pembrolizumab en combinaison ou non avec une chimiothérapie
Background : Programmed death-ligand 1 (PD-L1) immunohistochemistry is a predictive biomarker for anti-PD-(L)1 therapy in non-small cell lung cancer (NSCLC). It is not a reliable predictor of clinical benefit with non-invasive imaging providing a potential solution. We present the PECan study, the aim of which to assess the relationship of [99mTc]-labeled anti-PD-L1 single-domain antibody (NM-01) single-photon emission computed tomography (SPECT)/CT with metabolic response to anti-PD-(L)1.
Methods : PD-L1 tumour proportion score (TPS) measured using SP263 assay. [99mTc]NM-01 SPECT/CT and [18F]FDG PET/CT performed before and 9-weeks following pembrolizumab with/without chemotherapy in patients with advanced NSCLC. Tumor (T) to blood pool (BP) maximum region of interest (ROImax) measurements performed in primary and metastatic lesions using SPECT/CT images.
Results : Fifteen patients were included (median age 63 years, 9 male). Intertumoural heterogeneity evident in 10(67%) patients. Mean [99mTc]NM-01 T:BP demonstrated moderate correlation with PD-L1 TPS (r = 0.45, p < 0.05). Depth of [18F]FDG PET/CT metabolic response at 9-weeks (n = 13), correlated strongly with baseline [99mTc]NM-01 T:BP (r = −0.73, p < 0.05), but only moderately with PD-L1 TPS (r = −0.46, p = 0.06).
Conclusion : [99mTc]NM-01 SPECT/CT allows non-invasive quantification of PD-L1 in primary tumour and metastases in NSCLC. [99mTc]NM-01 uptake moderately correlates with PD-L1 immunohistochemistry, determines heterogeneity, and is associated with early metabolic response to anti-PD-1 pembrolizumab.
Clinical trials registration : PD-L1 Expression in Cancer (PECan) study (NCT04436406), registered 18 June 2020 https://clinicaltrials.gov/ct2/show/NCT04436406
British Journal of Cancer , article en libre accès 2025