ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Gallium-68-labeled Peptide PET Quantifies Tumor Exposure of PD-L1 Therapeutics.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- SuFEx and macrocyclic chelation define orthogonal reactivity domains enabling isotopically versatile radiopharmaceuticals from a single peptide precursor.bioRxiv : the preprint server for biology · 2026Article
- PD-L1 Expression as a Predictor of Time to Progression in Metastatic Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors: A Retrospective Single-Center Study.Journal of clinical medicine · 2026Article
- Nectin-4 PET for predicting enfortumab vedotin dose-response in urothelial carcinoma.Science advances · 2026Article
- Synthesis and Preclinical Evaluation of Dual-Targeted Molecular Tracer for Positron Emission Tomography Imaging of Programmed Cell Death Ligand‑1 and Integrin αACS pharmacology & translational science · 2025Article
- 68Ga-NK224 PET/CT for Noninvasive Evaluation of PD-L1 Expression and Intertumor Heterogeneity: A Translational Exploratory Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Article
- Preclinical evaluation and preliminary clinical study ofCancer imaging : the official publication of the International Cancer Imaging Society · 2025Article
- PD-1 and PD-L1 Expression in Endometrial Cancer: A Systematic Review of the Literature.Journal of clinical medicine · 2025Review
- EphA2-targeted alpha-particle theranostics for enhancing PDAC treatment.Theranostics · 2025Article
- Quantum Entanglement Filtering: A PET feasibility study in imaging dual-positron and prompt gamma emission via Monte Carlo simulation.IEEE transactions on radiation and plasma medical sciences · 2024Article
- Use of Upadacitinib to Treat a Severe Flare-Up of Rheumatoid Arthritis During Anti-PD-1 Immune Checkpoint Inhibitor Therapy for Stage IV Squamous Cell Carcinoma of the Lung.Journal of clinical medicine · 2024Article
- [European journal of nuclear medicine and molecular imaging · 2024Article
- Modulation of the tumor microenvironment and mechanism of immunotherapy-based drug resistance in breast cancer.Molecular cancer · 2024Review
- CD38-Specific Gallium-68 Labeled Peptide Radiotracer Enables Pharmacodynamic Monitoring in Multiple Myeloma with PET.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Navigating the landscape of PD-1/PD-L1 imaging tracers: from challenges to opportunities.Frontiers in medicine · 2024Review
- Investigating the Role ofInternational journal of molecular sciences · 2023Article
- Recent Advancement of PD-L1 Detection Technologies and Clinical Applications in the Era of Precision Cancer Therapy.Journal of Cancer · 2023Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
purposeImmune checkpoint therapy (ICT) is currently ineffective in a majority of patients. Tumor drug exposure measurements can provide vital insights into mechanisms involved in the resistance of solid tumors to those therapeutics; however, tools to quantify in situ drug exposure are few. We have investigated the potential of programmed death-ligand 1 (PD-L1) pharmacodynamics, quantified using PET, to inform on the tumor exposure of anti-PD-L1 (aPD-L1) therapeutics. EXPERIMENTAL
designTo noninvasively quantify PD-L1 levels, we first developed a novel peptide-based gallium-68-labeled binder, [68Ga]Ga-DK223, and evaluated its in vivo distribution, pharmacokinetics, and PD-L1 specificity in preclinical models of triple-negative breast cancer and urothelial carcinoma with variable PD-L1 expression. We then quantified baseline and accessible PD-L1 levels in tumors as a noninvasive pharmacodynamic measure to assess tumor exposure to two aPD-L1 antibodies (avelumab and durvalumab).
resultsDK223 exhibited a KD of 1.01±0.83 nmol/L for PD-L1 and inhibited the PD-1:PD-L1 interaction in a dose-dependent manner. [68Ga]Ga-DK223 provides high-contrast PET images within 60 minutes of administration and detects PD-L1 in an expression-dependent manner in xenograft models. PD-L1 pharmacodynamics measured using [68Ga]Ga-DK223-PET revealed that avelumab and durvalumab had similar exposure early during therapy, but only durvalumab exhibited sustained exposure at the tumor.
conclusions[68Ga]Ga-DK223 detected variable PD-L1 levels and exhibited salient features required for clinical translation. [68Ga]Ga-DK223-PET could be useful for quantifying total PD-L1 levels at baseline and accessible PD-L1 levels during therapy to understand drug exposure at the tumor, thus supporting its use for guiding and optimizing ICT.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.