[89Zr]-immuno-PET prediction of response to rituximab treatment in patients with therapy refractory interstitial pneumonitis: a phase 2 trial

• Published in: European journal of nuclear medicine and molecular imaging Vol. 50; no. 7; pp. 1929 - 1939
• Main Authors: Adams, H., van de Garde, E. M. W., Vugts, D. J., Grutters, J. C., Oyen, Wim. J.G., Keijsers, R. G.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-06-2023; Springer Nature B.V
• Subjects: Biomarkers; Carbon monoxide; Cardiology; CD20 antigen; Drug dosages; Health services; Hospitals; Humans; Imaging; Immunotherapy; Infection and inflammation; Lung; Lung diseases; Lung Diseases, Interstitial - diagnostic imaging; Lung Diseases, Interstitial - drug therapy; Lungs; Medical imaging; Medicine; Medicine & Public Health; Multidisciplinary teams; Nuclear Medicine; Oncology; Original; Original Article; Orthopedics; Patients; Pneumonitis; Positron emission; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prospective Studies; Pulmonary functions; Pulmonology; Radioisotopes - therapeutic use; Radiology; Respiratory function; Rituximab; Rituximab - adverse effects; Therapy; Zirconium; Zirconium isotopes; CD20; Rituximab; 89Zr-rituximab; PET-CT; Immuno PET; Interstitial lung disease
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-023-06143-1

Introduction
Immune-mediated interstitial pneumonitis may be treated with anti-CD20 therapy after failure of conventional therapies. However, clinical response is variable. It was hypothesized that autoreactive CD20-positive cells may play an important role in this variability. This prospective study aims to elucidate if imaging of CD20-positive cells in the lungs allows prediction of the response to anti-CD20 treatment.
Methods
Twenty-one patients with immune-mediated interstitial lung disease (ILD) with deteriorated pulmonary function received a dose of 1000 mg rituximab on day 1 and day 14 spiked with a tracer dose of radiolabeled [89Zr]-rituximab. PET/CT was performed on days 3 and 6. Standardized uptake values (SUV) were calculated as a measure for pulmonary CD20 expression. Based on pulmonary function tests (PFT), forced vital capacity (FVC), and diffusing capacity for carbon monoxide (DLCO), prior to and 6 months after treatment, patients were classified as responder (stable disease or improvement) or non-responder.
Results
Fifteen patients (71%) were classified as responder. Pulmonary [89Zr]-rituximab PET SUVmean was significantly correlated with the change in FVC and DLCO (
K
= 0.49 and 0.56, respectively) when using target-to-background ratios, but not when using SUVmean alone. [89Zr]-rituximab SUVmean was significantly higher in responders than in non-responders (0.35 SD 0.09 vs. 0.23 SD 0.06;
P
= 0.02).
Conclusion
Rituximab treatment was effective in the majority of patients. As a higher pulmonary uptake of [89Zr]-rituximab correlated with improvement of PFT and treatment outcome, [89Zr]-rituximab PET imaging may serve as a potential predictive biomarker for anti-CD20 therapy.
Trial registration
Clinicaltrials.gov identifier NCT02251964