Immuno-PET Imaging of Tumour PD-L1 Expression in Glioblastoma.
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Embargo End Date
ICR Authors
Authors
Sharma, G
Braga, MC
Da Pieve, C
Szopa, W
Starzetz, T
Plate, KH
Kaspera, W
Kramer-Marek, G
Braga, MC
Da Pieve, C
Szopa, W
Starzetz, T
Plate, KH
Kaspera, W
Kramer-Marek, G
Document Type
Journal Article
Date
2023-06-09
Date Accepted
2023-06-08
Abstract
There is no established method to assess the PD-L1 expression in brain tumours. Therefore, we investigated the suitability of affibody molecule (ZPD-L1) radiolabelled with F-18 (Al18F) and Ga-68 to measure the expression of PD-L1 in xenograft mouse models of GBM. Mice bearing subcutaneous and orthotopic tumours were imaged 1 h post-radioconjugate administration. Ex vivo biodistribution studies and immunohistochemistry (IHC) staining were performed. Tumoural PD-L1 expression and CD4+/CD8+ tumour-infiltrating lymphocytes were evaluated in human GBM specimens. ZPD-L1 was radiolabelled with radiochemical yields of 32.2 ± 4.4% (F-18) and 73.3 ± 1.8% (Ga-68). The cell-associated radioactivity in vitro was consistent with PD-L1 expression levels assessed with flow cytometry. In vivo imaging demonstrated that 18F-AlF-NOTA-ZPD-L1 can distinguish between PD-L1 high-expressing tumours (U87-MGvIII) and PD-L1-negative ones (H292PD-L1Ko). The radioconjugate was quickly cleared from the blood and normal tissues, allowing for high-contrast images of brain tumours as early as 1 h post-injection. 68Ga-NOTA-ZPD-L1 showed heterogeneous and diffuse accumulation that corresponded to the extensively infiltrating GCGR-E55 tumours involving contiguous lobes of the brain. Lastly, 39% of analysed GBM patient samples showed PD-L1+ staining of tumour cells that was associated with elevated levels of CD4+ and CD8+ lymphocytes. Our results suggest that the investigated radioconjugates are very promising agents with the potential to facilitate the future design of treatment regimens for GBM patients.
Citation
Cancers, 2023, 15 (12), pp. 3131 -
Source Title
Cancers
Publisher
MDPI
ISSN
2072-6694
eISSN
2072-6694
2072-6694
2072-6694
Collections
Research Team
Preclin Molecular Imaging