Dataset Information

Rapid PD-L1 detection in tumors with PET using a highly specific peptide.

ABSTRACT: Molecular imaging can report on the status of the tumor immune microenvironment and guide immunotherapeutic strategies to enhance the efficacy of immune modulation therapies. Imaging agents that can rapidly report on targets of immunomodulatory therapies are few. The programmed death ligand 1 (PD-L1) is an immune checkpoint protein over-expressed in several cancers and contributes to tumor immune suppression. Tumor PD-L1 expression is indicative of tumor response to PD-1 and PD-L1 targeted therapies. Herein, we report a highly specific peptide-based positron emission tomography (PET) imaging agent for PD-L1. We assessed the binding modes of the peptide WL12 to PD-L1 by docking studies, developed a copper-64 labeled WL12 ([64Cu]WL12), and performed its evaluation in vitro, and in vivo by PET imaging, biodistribution and blocking studies. Our results show that [64Cu]WL12 can be used to detect tumor PD-L1 expression specifically and soon after injection of the radiotracer, to fit within the standard clinical workflow of imaging within 60 min of administration.

SUBMITTER: Chatterjee S

PROVIDER: S-EPMC5253331 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Rapid PD-L1 detection in tumors with PET using a highly specific peptide.

Chatterjee Samit S Lesniak Wojciech G WG Miller Michelle S MS Lisok Ala A Sikorska Emilia E Wharram Bryan B Kumar Dhiraj D Gabrielson Matthew M Pomper Martin G MG Gabelli Sandra B SB Nimmagadda Sridhar S

Biochemical and biophysical research communications 20161224 1

Molecular imaging can report on the status of the tumor immune microenvironment and guide immunotherapeutic strategies to enhance the efficacy of immune modulation therapies. Imaging agents that can rapidly report on targets of immunomodulatory therapies are few. The programmed death ligand 1 (PD-L1) is an immune checkpoint protein over-expressed in several cancers and contributes to tumor immune suppression. Tumor PD-L1 expression is indicative of tumor response to PD-1 and PD-L1 targeted thera ...[more]

PMID: 28025143

Similar Datasets

Project description:PurposeDespite 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, and improve overall response rates. However, tissue-based methods are invasive and prone to sampling error. We therefore developed a PET radiotracer to specifically detect PD-L1 expression in a non-invasive manner, which could be of diagnostic and predictive value.MethodsAnti-PD-L1 (clone 6E11, Genentech) was site-specifically conjugated with DIBO-DFO and radiolabelled with 89Zr (89Zr-DFO-6E11). 89Zr-DFO-6E11 was optimized in vivo by longitudinal PET imaging and dose escalation with excess unlabelled 6E11 in HCC827 tumour-bearing mice. Specificity of 89Zr-DFO-6E11 was evaluated in NSCLC xenografts and syngeneic tumour models with different levels of PD-L1 expression. In vivo imaging data was supported by ex vivo biodistribution, flow cytometry, and IHC. To evaluate the predictive value of 89Zr-DFO-6E11 PET imaging, CT26 tumour-bearing mice were subjected to external radiation therapy (XRT) in combination with PD-L1 blockade.Results89Zr-DFO-6E11 was successfully labelled with a high radiochemical purity. The HCC827 tumours and lymphoid tissue were identified by 89Zr-DFO-6E11 PET imaging, and co-injection with 6E11 increased the relative tumour uptake and decreased the splenic uptake. 89Zr-DFO-6E11 detected the differences in PD-L1 expression among tumour models as evaluated by ex vivo methods. 89Zr-DFO-6E11 quantified the increase in PD-L1 expression in tumours and spleens of irradiated mice. XRT and anti-PD-L1 therapy effectively inhibited tumour growth in CT26 tumour-bearing mice (p < 0.01), and the maximum 89Zr-DFO-6E11 tumour-to-muscle ratio correlated with response to therapy (p = 0.0252).ConclusionPET imaging with 89Zr-DFO-6E11 is an attractive approach for specific, non-invasive, whole-body visualization of PD-L1 expression. PD-L1 expression can be modulated by radiotherapy regimens and 89Zr-DFO-6E11 PET is able to monitor these changes and predict the response to therapy in an immunocompetent tumour model.

Dataset Information

Rapid PD-L1 detection in tumors with PET using a highly specific peptide.

Publications

Rapid PD-L1 detection in tumors with PET using a highly specific peptide.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets