Non-invasive PD-L1 quantification using [18 F]DK222-PET imaging in cancer immunotherapy

Sep 24, 2026

Uploaded by Stanley

Non-invasive, early pharmacodynamic biomarkers are needed to improve combination strategies for immune checkpoint inhibitor therapy. Positron emission tomography (PET) was used to monitor target dynamics, focusing on programmed death-ligand 1 (PD-L1) expression. [18F]DK222, a peptide-based PD-L1 imaging agent, was evaluated in humanized mouse models to relate PD-L1 expression with therapy-induced changes. PET quantification assessed anti–PD-1 effects in tumors with and without MSI and validated pharmacodynamics in monotherapy and combination settings using melanoma xenografts.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusion

What this study adds

How this study might affect research, practice or policy

Open access Original research To cite: Mishra A, Gupta K, Kumar D, et al. Non-invasive PD-L1 quantification using [18F] DK222-PET imaging in cancer immunotherapy. Journal for ImmunoTherapy of Cancer 2023;11:e007535 . doi:10 . 1136/ jitc-2023-007535 ► Additional supplemental material is published online only. To view, please visit the journal online ([http://dx.doi.org/10](http://dx.doi.org/10) . 1136/jitc-2023-007535) . Accepted 03 September 2023 © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. For numbered affiliations see end of article. Correspondence to Dr Sridhar Nimmagadda; [snimmag1@jhmi.edu](snimmag1@jhmi.edu) Non-invasive PD-L1 quantification using [18 F]DK222-PET imaging in cancer immunotherapy Akhilesh Mishra ,1,2 Kuldeep Gupta ,1 Dhiraj Kumar,1 Gabriela Lofland,1 Ajay Kumar Sharma ,1 Lilja B Solnes,1 Steven P Rowe,1 Patrick M Forde,3 Martin G Pomper,1,3,4 Edward W Gabrielson,3,5 Sridhar Nimmagadda 1,3,4,6 ABSTRACT Background Combination therapies that aim to improve the clinical efficacy to immune checkpoint inhibitors have led to the need for non-invasive and early pharmacodynamic biomarkers. Positron emission tomography (PET) is a promising non-invasive approach to monitoring target dynamics, and programmed deathligand 1 (PD-L1) expression is a central component in cancer immunotherapy strategies. [18F]DK222, a peptidebased PD-L1 imaging agent, was investigated in this study using humanized mouse models to explore the relationship between PD-L1 expression and therapy-induced changes in cancer. Methods Cell lines and xenografts derived from three non-small cell lung cancers (NSCLCs) and three urothelial carcinomas (UCs) were used to validate the specificity of [18F]DK222 for PD-L1 . PET was used to quantify anti-programmed cell death protein-1 (PD-1) therapyinduced changes in PD-L1 expression in tumors with and without microsatellite instability (MSI) in humanized mice. Furthermore,[18F]DK222-PET was used to validate PD-L1 pharmacodynamics in the context of monotherapy and combination immunotherapy in humanized mice bearing A375 melanoma xenografts. PET measures of PD-L1 expression were used to establish a relationship between pathological and immunological changes. Lastly, spatial distribution analysis of [18F]DK222-PET was developed to assess the effects of different immunotherapy regimens on tumor heterogeneity. Results [18F]DK222-PET and biodistribution studies in mice with NSCLC and UC xenografts revealed high but variable tumor uptake at 60 min that correlated with PD-L1 expression. In MSI tumors treated with antiPD-1,[18F]DK222 uptake was higher than in control tumors. Moreover, [18F]DK222 uptake was higher in A375 tumors treated with combination therapy compared with monotherapy, and negatively correlated with final tumor volumes. In addition, a higher number of PD-L1+ cells and higher CD8+-to-CD4+ cell ratio was observed with combination therapy compared with monotherapy, and positively correlated with PET. Furthermore, spatial distribution analysis showed higher [18F]DK222 uptake towards the core of the tumors in combination therapy, indicating a more robust and distinct pattern of immune cell infiltration. Conclusion [18F]DK222-PET has potential as a noninvasive tool for monitoring the effects of immunotherapy | WHAT IS ALREADY KNOWN ON THIS TOPIC | | --- | | ⇒ While cancer immunotherapy with immune checkpoint inhibitors (ICI) has advanced survival rates, it remains effective for only a subset of patients. Thereis a pressing need to precisely forecast therapeutic results and overall patient survival subsequent to ICI treatments. A common occurrence post-ICI therapy is the surge in programmed death-ligand 1 (PD-L1) expression at the tumor site due to immune cell infiltration. Yet, there is a scarcity of tools designed to track these dynamic changes in PD-L1 expression, both pr

FAQs

What is the purpose of using [18F]DK222-PET in this study?

To non-invasively quantify PD-L1 expression dynamics and assess therapy-induced changes during cancer immunotherapy.

How was PET used to evaluate PD-L1 changes after treatment?

PET quantification measured anti–PD-1 therapy–induced changes in PD-L1 expression in tumors with and without microsatellite instability (MSI) using humanized mouse models.

What differences were observed between combination therapy and monotherapy?

Combination therapy produced higher [18F]DK222 uptake in A375 tumors than monotherapy, along with immune-cell changes (including a higher number of PD-L1+ cells and a higher CD8+ to CD4+ ratio) that correlated with PET measures.

Sep 24, 2026

Uploaded by Stanley