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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Early identification of antigen-specific immune responses in vivo by [~(18)F]-labeled 3'-fluoro- 3'-deoxy-thymidine ([~(18)F]FLT) PET imaging
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Early identification of antigen-specific immune responses in vivo by [~(18)F]-labeled 3'-fluoro- 3'-deoxy-thymidine ([~(18)F]FLT) PET imaging

机译：通过[〜（18）F]标记的3'-氟-3'-脱氧胸苷（[〜（18）F] FLT）PET成像对体内抗原特异性免疫反应的早期鉴定

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摘要

Current biomarkers are unable to adequately predict vaccine-induced immune protection in humans with infectious disease or cancer. However, timely and adequate assessment of antigen-specific immune responses is critical for successful vaccine development. Therefore, we have developed a method for the direct assessment of immune responses in vivo in a clinical setting. Melanoma patients with lymph node (LN) metastases received dendritic cell (DC) vaccine therapy, injected intranodally, followed by [~(18)F]-labeled 3-fluoro-3'-deoxy-thymidine ([~(18)F]FLT) PET at varying time points after vaccination. Control LNs received saline or DCs without antigen. De novo immune responses were readily visualized in treated LNs early after the prime vaccination, and these signals persisted for up to 3 wk. This selective [~(18)F]FLT uptake was markedly absent in control LNs, although tracer uptake in treated LNs increased profoundly with as little as 4.5 × 10~5 DCs. Immunohis-tochemical staining confirmed injected DC dispersion to T-cell areas and resultant activation of CD4~+ and CDS~+ T cells. The level of LN tracer uptake significantly correlates to the level of circulating antigen-specific IgG antibodies and antigen-specific proliferation of T cells in peripheral blood. Furthermore, this correlation was not observed with [~(18)F]-labeled fluoro-2-deoxy-2-D-glucose. Therefore, [~(18)F]FLT PET offers a sensitive tool to study the kinetics, localization, and involvement of lymphocyte subsets in response to vaccination. This technique allows for early discrimination of responding from nonresponding patients in anti-cancer vaccination and aid physicians in individualized decisionmaking.
机译：当前的生物标记物不能充分预测感染性疾病或癌症的人的疫苗诱导的免疫保护。但是，及时，充分地评估抗原特异性免疫反应对于成功开发疫苗至关重要。因此，我们开发了一种在临床环境中直接评估体内免疫反应的方法。患有淋巴结（LN）转移的黑色素瘤患者接受树突状细胞（DC）疫苗治疗，结节内注射，然后进行[〜（18）F]标记的3-fluoro-3'-deoxy-thymidine（[〜（18）F]疫苗接种后不同时间点的FLT）PET。对照LN接受不含抗原的盐水或DC。初次接种疫苗后，在治疗的LN中很容易看到从头免疫反应，这些信号持续长达3周。对照LNs明显缺乏这种选择性的[〜（18）F] FLT摄取，尽管经处理的LNs的示踪剂摄取显着增加，只有4.5×10〜5个DC。免疫化学染色证实注入的DC分散到T细胞区域，并导致CD4〜+和CDS〜+ T细胞活化。 LN示踪剂摄取水平与外周血中循环的抗原特异性IgG抗体水平和T细胞的抗原特异性增殖水平显着相关。此外，用[〜（18）F]标记的氟-2-脱氧-2-D-葡萄糖未观察到这种相关性。因此，[〜（18）F] FLT PET提供了一种灵敏的工具来研究免疫接种后淋巴细胞亚群的动力学，定位和参与。该技术可以早期区分抗癌疫苗接种中无反应的患者的反应，并帮助医生进行个性化决策。

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  • 作者

    Erik H. J. G. Aarntzen; Mangala Srinivas; Johannes H. W. De Wilt; Joannes F. M. Jacobs; W. Joost Lesterhuis; Albert D. Windhorst; Esther G. Troost; Johannes J. Bonenkamp; Michelle M. van Rossum; Willeke A. M. Blokx; Roel D. Mus; Otto C. Boerman; Cornelis J. A. Punt; Carl G. Figdor; Wim J. G. Oyen; I. Jolanda M. de Vries;

  • 作者单位

    Departments of Tumor Immunology, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands,Departments of Medical Oncology, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands;

    Departments of Tumor Immunology, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands;

    Departments of Surgery,Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands;

    Departments of Tumor Immunology, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands,Departments of Medical Oncology, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands,Departments of Laboratory Medical Immunology, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands;

    Departments of Tumor Immunology, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands,Departments of Medical Oncology, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands;

    Department of Nuclear Medicine and PET Centre, Free University (VU) Medical Centre, 1007 MB, Amsterdam, The Netherlands;

    Departments of Radiotherapy, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands;

    Departments of Surgery,Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands;

    Departments of Dermatology, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands;

    Departments of Pathology, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands;

    Departments of Radiology,Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands;

    Departments of Nudear Medicine, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands;

    Departments of Medical Oncology, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands,Academic Medical Center, Department of Medical Oncology, 1105 AZ, Amsterdam, The Netherlands;

    Departments of Tumor Immunology, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands;

    Departments of Nudear Medicine, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands;

    Departments of Tumor Immunology, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands,Departments of Medical Oncology, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    individualized treatment; molecular imaging; immune monitoring; cellular therapy;

    机译：个性化治疗;分子成像免疫监测;细胞疗法;

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