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• W2938932250 abstract "Immune checkpoint expression is highly dynamic, and combination treatments including radiotherapy can particularly modulate this expression. PET imaging using 89Zr–Df–atezolizumab can provide insight into the levels of PD-L1 variation following radiotherapy treatments. In vitro screening was used to monitor PD-L1 expression by lung cancer cells following radiotherapy. Mice bearing PD-L1+ (H460) or PD-L1- (A549) tumors were subjected to various external beam radiotherapy regimens and then imaged using 89Zr–Df–atezolizumab PET. ROI analysis and ex vivo biodistribution studies were employed to quantify tracer accumulations. H460 cells were found to have PD-L1 expression at baseline, and this expression increased following daily radiotherapy of 5 fractions of 2 Gy. PD-L1 expression could not be induced on A549 cells, regardless of radiotherapy regimen. The increase in PD-L1 expression in H460 tumors following fractionated radiotherapy could be imaged in vivo using 89Zr–Df–atezolizumab, with statistically significant higher tracer accumulation noted in fractionated H460 tumors over that in all other H460 or A549 groups after 72 h postinjection of the tracer. Significant accumulation of the tracer was also noted in other PD-L1+ organs, including the spleen and lymph nodes. Ex vivo staining of tumor tissues verified that tumor cells as well as tumor-infiltrating immune cells were responsible for increased PD-L1 expression after radiotherapy in tumor tissues. Overall, PD-L1 expression can be modulated with radiotherapy interventions, and 89Zr–Df–atezolizumab is able to noninvasively monitor these changes in preclinical models." @default.
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• W2938932250 date "2019-04-11" @default.
• W2938932250 modified "2023-10-16" @default.
• W2938932250 title "Noninvasive Imaging and Quantification of Radiotherapy-Induced PD-L1 Upregulation with ⁸⁹Zr–Df–Atezolizumab" @default.
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• W2938932250 doi "https://doi.org/10.1021/acs.bioconjchem.9b00178" @default.
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