PD-L1 PET/CT Imaging with Radiolabeled Durvalumab in Patients with Advanced-Stage Non-Small Cell Lung Cancer

• Published in: Journal of Nuclear Medicine Vol. 63; no. 5; pp. 686 - 693
• Main Authors: Smit, Jasper, Borm, Frank J, Niemeijer, Anna-Larissa N, Huisman, Marc C, Hoekstra, Otto S, Boellaard, Ronald, Oprea-Lager, Daniela E, Vugts, Danielle J, van Dongen, Guus A M S, de Wit-van der Veen, Berlinda J, Thunnissen, Erik, Smit, Egbert F, de Langen, Adrianus J
• Format: Journal Article
• Language: English
• Published: United States Society of Nuclear Medicine 01-05-2022
• Subjects: Adverse events; Antibodies, Monoclonal; Apoptosis; B7-H1 Antigen - metabolism; Biodistribution; Biomarkers; Blood; Carcinoma, Non-Small-Cell Lung - diagnostic imaging; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Computed tomography; Health services; Heterogeneity; Humans; Image acquisition; Immune checkpoint; Immune system; Immunohistochemistry; Immunotherapy; Injection; Lesions; Lung cancer; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Medical imaging; Monoclonal antibodies; Non-small cell lung carcinoma; Patients; PD-1 protein; PD-L1 protein; Positron emission; Positron Emission Tomography Computed Tomography; Small cell lung carcinoma; Spleen; Statistical analysis; Targeted cancer therapy; Tissue Distribution; Tomography; Tumor cells; Tumors; Zirconium isotopes; non–small cell lung cancer; PD-L1 inhibitor; PET imaging; immunotherapy
• ISSN: 0161-5505; 1535-5667; 2159-662X
• DOI: 10.2967/jnumed.121.262473

Better biomarkers are needed to predict treatment outcome in non-small cell lung cancer (NSCLC) patients treated with anti-programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint inhibitors. PD-L1 immunohistochemistry has limited predictive value, possibly because of tumor heterogeneity of PD-L1 expression. Noninvasive PD-L1 imaging using
Zr-durvalumab might better reflect tumor PD-L1 expression.
NSCLC patients eligible for second-line immunotherapy were enrolled. Patients received 2 injections of
Zr-durvalumab: one without a preceding dose of unlabeled durvalumab (tracer dose only) and one with a preceding dose of 750 mg of durvalumab, directly before tracer injection. Up to 4 PET/CT scans were obtained after tracer injection. After imaging acquisition, patients were treated with 750 mg of durvalumab every 2 wk. Tracer biodistribution and tumor uptake were visually assessed and quantified as SUV, and both imaging acquisitions were compared. Tumor tracer uptake was correlated with PD-L1 expression and clinical outcome, defined as response to durvalumab treatment.
Thirteen patients were included, and 10 completed all scheduled PET scans. No tracer-related adverse events were observed, and all patients started durvalumab treatment. Biodistribution analysis showed
Zr-durvalumab accumulation in the blood pool, liver, and spleen. Serial imaging showed that image acquisition 120 h after injection delivered the best tumor-to-blood pool ratio. Most tumor lesions were visualized with the tracer dose only versus the coinjection imaging acquisition (25% vs. 13.5% of all lesions). Uptake heterogeneity was observed within (SUV
range, 0.2-15.1) and between patients. Tumor uptake was higher in patients with treatment response or stable disease than in patients with disease progression according to RECIST 1.1. However, this difference was not statistically significant (median SUV
, 4.9 vs. 2.4;
= 0.06). SUV
correlated better with the combined tumor and immune cell PD-L1 score than with PD-L1 expression on tumor cells, although neither was statistically significant (
= 0.06 and
= 0.93, respectively).
Zr-durvalumab was safe, without any tracer-related adverse events, and more tumor lesions were visualized using the tracer dose-only imaging acquisition.
Zr-durvalumab tumor uptake was higher in patients with a response to durvalumab treatment but did not correlate with tumor PD-L1 immunohistochemistry.