Imaging PD-L1 in the brain-Journey from the lab to the clinic.
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Embargo End Date
ICR Authors
Authors
Dar, D
Rodak, M
Da Pieve, C
Gorczewska, I
Sharma, G
Chmielik, E
Niedbala, M
Bzowski, P
d'Amico, A
Bobek-Billewicz, B
Nowicka, E
Tarnawski, R
Kaspera, W
Kramer-Marek, G
Rodak, M
Da Pieve, C
Gorczewska, I
Sharma, G
Chmielik, E
Niedbala, M
Bzowski, P
d'Amico, A
Bobek-Billewicz, B
Nowicka, E
Tarnawski, R
Kaspera, W
Kramer-Marek, G
Document Type
Conference Proceeding
Date
2024-10-28
Date Accepted
Abstract
BACKGROUND: Immune checkpoint inhibitors (ICPIs) have proven to restore adaptive anti-tumor immunity in many cancers; however, no noteworthy therapeutic schedule has been established for patients with glioblastoma (GBM). High programmed death-ligand 1 (PD-L1) expression is associated with immunosuppressive and aggressive phenotypes in GBM. Presently, there is no standardized protocol for assessing PD-L1 expression levels to select patients and monitor their response to ICPI therapy. The aim of this study was to investigate the use of 89Zr-DFO-Atezolizumab to image the spatio-temporal distribution of PD-L1 in preclinical mouse models and in patients with newly diagnosed GBM treated with/without neoadjuvant Pembrolizumab. METHODS: The immunoreactivity, binding affinity, and specificity of 89Zr-DFO-Atezolizumab were confirmed in vitro. Mice-bearing orthotopic GBM tumors or patients with newly diagnosed GBM treated with/without Pembrolizumab were intravenously injected with 89Zr-DFO-Atezolizumab, and PET/CT images were acquired 24, 48, and 72 hours in mice and at 48 and 72 post-injection in patients. Radioconjugate uptake was quantified in the tumor and healthy tissues. Ex vivo immunohistochemistry (IHC) and immunophenotyping were performed on mouse tumor samples or resected human tumors. RESULTS: 89Zr-DFO-Atezolizumab was prepared with high radiochemical purity (RCP > 99%). In vitro cell-associated radioactivity of 89Zr-DFO-Atezolizumab corroborated cell line PD-L1 expression. PD-L1 in mouse GBM tumors was detected with high specificity using 89Zr-DFO-Atezolizumab and radioconjugate uptake correlated with IHC. Patients experienced no 89Zr-DFO-Atezolizumab-related side effects. High 89Zr-DFO-Atezolizumab uptake was observed in patient tumors at 48 hours post-injection, however, the uptake varied between patients treated with/without Pembrolizumab. CONCLUSIONS: 89Zr-DFO-Atezolizumab can visualize distinct PD-L1 expression levels with high specificity in preclinical mouse models and in patients with GBM, whilst complementing ex vivo analysis.
Citation
Neuro-Oncology, 2024, 50 (SUPPL 1), pp. noae190 -
Source Title
Neuro-Oncology
Publisher
OXFORD UNIV PRESS INC
ISSN
1522-8517
eISSN
1523-5866
Collections
Research Team
Preclin Molecular Imaging