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Noninvasive Monitoring of Immunotherapy in Lung Cancer by Lymphocyte Activation Gene 3 PET Imaging of Tumor-Infiltrating Lymphocytes

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机构： [1]Department of Nuclear Medicine, Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China [2]NHC Key Laboratoryof Molecular Probe and Targeted Diagnosis and Therapy, Molecular Imaging Research Center (MIRC) of Harbin Medical University,Harbin, Heilongjiang, China [3]Biomedical Research Imaging Center (BRIC), The University of North Carolina at Chapel Hill, ChapelHill, North Carolina [4]Department of Hematology, Shandong Cancer Hospital and Institute, Shandong First Medical University andShandong Academy of Medical Sciences, Jinan, Shandong, China [5]Department of Nuclear Medicine and Laboratory of ClinicalNuclear Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China

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关键词： lung cancer immunotherapy LAG-3 TIL PET

摘要：

Although immunotherapy has revolutionized the entire cancer treatment landscape, small fractions of patients respond to immunotherapy. Early identification of responders may improve patient management during immunotherapy. In this study, we evaluated a PET approach for monitoring immunotherapy in lung cancer by imaging the upregulation of lymphocyte activation gene 3 (LAG-3)-expressing (LAG-3+) tumor-infiltrating lymphocytes (TILs). Methods: We synthesized a LAG-3-targeted molecular imaging probe, [68Ga]Ga-NOTA-C25 and performed a series of in vitro and in vivo assays to test its specificity. Next, [68Ga]Ga-NOTA-C25 PET was used to monitor immunotherapy in murine lung cancer-bearing mice and in humanized mouse models for assessing clinical translational potential, with confirmation by immunostaining and flow cytometry analysis. Results: [68Ga]Ga-NOTA-C25 PET could noninvasively detect intertumoral differences in LAG-3+ TIL levels in different tumor models. Importantly, in Lewis lung carcinoma tumor models treated with an agonist of a stimulator of interferon genes, [68Ga]Ga-NOTA-C25 PET also detected an immunophenotyping transition of the tumor from "cold" to "hot" before changes in tumor size. Meanwhile, animals carrying "hot" tumor showed more significant tumor inhibition and longer survival than those carrying "cold" tumor. [68Ga]Ga-NOTA-C25 PET also showed markedly higher tumor uptake in immune system-humanized mice carrying human non-small cell lung cancer than immunodeficient models. Conclusion: [68Ga]Ga-NOTA-C25 PET could be used to noninvasively monitor the early response to immunotherapy by imaging LAG-3+ TILs in lung cancer. [68Ga]Ga-NOTA-C25 PET also exhibited excellent translational potential, with great significance for the precise management of lung cancer patients receiving immunotherapy.© 2024 by the Society of Nuclear Medicine and Molecular Imaging.

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出版当年[2023]版：

大类 | 1 区

医学

小类 | 2 区核医学

最新[2023]版：

大类 | 1 区

医学

小类 | 2 区核医学

第一作者：

第一作者机构： [1]Department of Nuclear Medicine, Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China [2]NHC Key Laboratoryof Molecular Probe and Targeted Diagnosis and Therapy, Molecular Imaging Research Center (MIRC) of Harbin Medical University,Harbin, Heilongjiang, China

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通讯作者：

通讯机构： [1]Department of Nuclear Medicine, Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China [2]NHC Key Laboratoryof Molecular Probe and Targeted Diagnosis and Therapy, Molecular Imaging Research Center (MIRC) of Harbin Medical University,Harbin, Heilongjiang, China

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Noninvasive Monitoring of Immunotherapy in Lung Cancer by Lymphocyte Activation Gene 3 PET Imaging of Tumor-Infiltrating Lymphocytes

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