ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025
68Ga-NK224 PET/CT for Noninvasive Evaluation of PD-L1 Expression and Intertumor Heterogeneity: A Translational Exploratory Study.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Prognostic value and diagnostic performance of nectin-4-targeted [European journal of nuclear medicine and molecular imaging · 2026Article
- Advances in PD-L1 Targeted Molecular Imaging Radiotracers Research: From Preclinical Exploration to Clinical Application.Molecular imaging and biology · 2026Review
- Fluorination augments tumor engagement and antitumor immunity of a D-peptide-based radiotheranostic agent for combinatorial immune checkpoint blockade therapy.Journal for immunotherapy of cancer · 2026Article
- Article
- Synthesis and Evaluation of [Pharmaceutics · 2025Article
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16 authors.
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Abstract
purposeThis study developed 68Ga-NK224, a novel peptide-based radiotracer targeting human PD-L1, to evaluate the feasibility of 68Ga-NK224 PET/CT for assessing PD-L1 expression and tumor heterogeneity in a prospective investigator-initiated trial. EXPERIMENTAL
designIn preclinical studies, NK224 was labeled with 68Ga. Small-animal PET, biodistribution, and blocking studies were performed using tumor models with varying PD-L1 expression levels to assess the targeting ability and specificity of 68Ga-NK224 in vivo. Serial 68Ga-NK224 PET assessed target occupancy following PD-L1 antibody administration. In the clinical study, 37 patients with non-small cell lung cancer who underwent 68Ga-NK224 PET/CT were prospectively recruited, with PD-L1 expression assessed via IHC and analyzed for correlation with 68Ga-NK224 uptake.
resultsPreclinical studies demonstrated that 68Ga-NK224 exhibited high tumor uptake and rapid clearance, producing favorable tumor-to-background contrast. In human CD34+ humanized mice, immunotherapy guided by 68Ga-NK224 PET/CT (once weekly) yielded similar antitumor effects as conventional dosing (three times weekly). Clinically, 68Ga-NK224 PET/CT was well tolerated, with no adverse events reported. Among the 31 patients who underwent paired 68Ga-NK224 and 2[18F]fluoro-2-deoxy-D-glucose PET/CT, the tumor uptake of 68Ga-NK224 significantly correlated with PD-L1 expression, whereas no correlation was found with 2[18F]fluoro-2-deoxy-D-glucose PET/CT. Additionally, 68Ga-NK224 demonstrated high heterogeneity across intrapatient lesions, with a median maximum standardized uptake value (SUVmax) coefficient of variation of 27.5% (range, 5.7%-53.2%).
conclusions68Ga-NK224 provides a straightforward radiolabeling approach with high tumor-to-background contrast, enabling an accurate assessment of PD-L1 expression and visualization of heterogeneity across intrapatient lesions. Its ability to dynamically monitor PD-L1 occupancy in tumors offers a novel method for optimizing immunotherapy dosing regimens.
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