1. [89Zr]-immuno-PET prediction of response to rituximab treatment in patients with therapy refractory interstitial pneumonitis: a phase 2 trial
- Author
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H. Adams, E. M. W. van de Garde, D. J. Vugts, J. C. Grutters, Wim. J.G. Oyen, R. G. Keijsers, Pharmacoepidemiology and Clinical Pharmacology, Sub Molecular Microbiology, Afd Pharmacoepi & Clinical Pharmacology, Radiology and nuclear medicine, AII - Cancer immunology, AII - Inflammatory diseases, CCA - Cancer biology and immunology, and CCA - Imaging and biomarkers
- Subjects
All institutes and research themes of the Radboud University Medical Center ,Radiology Nuclear Medicine and imaging ,PET-CT ,89Zr-rituximab ,Radiology, Nuclear Medicine and imaging ,CD20 ,Interstitial lung disease ,General Medicine ,Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] ,Rituximab ,Immuno PET - Abstract
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
- Published
- 2023