biostudies-literatureEhlerding EBNational Cancer InstituteNCI NIH HHSNational Institute of General Medical SciencesNIGMS NIH HHS1434-1441https://www.ebi.ac.uk/biostudies/studies/S-EPMC6521689biostudies-literatureUnknown30(5)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.Bioconjugate chemistryNoninvasive Imaging and Quantification of Radiotherapy-Induced PD-L1 Upregulation with ⁸⁹Zr-Df-Atezolizumab.PMC6521689T32 CA009206T32CA009206P30 CA014520P30CA014520T32 GM008505T32GM008505Engle JWBarnhart TEMcNeel DGLee HJJiang DEhlerding EBKang LCai WfalseNoninvasive Imaging and Quantification of Radiotherapy-Induced PD-L1 Upregulation with ⁸⁹Zr-Df-Atezolizumab.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.2019-01-01T00:00:00Z2019 May2024-02-15T12:50:04.145Z2020-10-29T10:06:26ZS-EPMC65216893097370310.1021/acs.bioconjchem.9b00178