Quantitative PET imaging of PD-L1 expression in xenograft and syngeneic tumour models using a site-specifically labelled PD-L1 antibody

• DOI: 10.1007/s00259-019-04646-4
• Publication Date: 2019-12-27T22:15:32Z
• Authors: Camilla Christensen; Lotte K. Kristensen; Maria Z. Alfsen; Carsten H. Nielsen; Andreas Kjaer
• Keywords: Biodistribution; Ex vivo

Abstract Purpose Despite remarkable clinical responses and prolonged survival across several cancers, not all patients benefit from PD-1/PD-L1 immune checkpoint blockade. Accordingly, assessment of tumour PD-L1 expression by immunohistochemistry (IHC) is increasingly applied to guide patient selection, therapeutic monitoring, improve overall response rates. However, tissue-based methods are invasive prone sampling error. We therefore developed a PET radiotracer specifically detect in non-invasive manner, which could be diagnostic predictive value. Methods Anti-PD-L1 (clone 6E11, Genentech) was site-specifically conjugated with DIBO-DFO radiolabelled 89 Zr ( Zr-DFO-6E11). Zr-DFO-6E11 optimized vivo longitudinal imaging dose escalation excess unlabelled 6E11 HCC827 tumour-bearing mice. Specificity evaluated NSCLC xenografts syngeneic models different levels expression. In data supported ex biodistribution, flow cytometry, IHC. To evaluate the value imaging, CT26 mice were subjected external radiation therapy (XRT) combination Results successfully labelled high radiochemical purity. The tumours lymphoid tissue identified co-injection increased relative uptake decreased splenic uptake. detected differences among as methods. quantified increase spleens irradiated XRT anti-PD-L1 effectively inhibited growth p < 0.01), maximum tumour-to-muscle ratio correlated = 0.0252). Conclusion an attractive approach for specific, non-invasive, whole-body visualization can modulated radiotherapy regimens able monitor these changes predict immunocompetent model.