In Vivo Detection of Lymph Nodes Metastasis of ESCC Using CXCR4-Targeted Tracer [⁶⁴Cu]Cu-NOTA-CP01.

IF 3 4区医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Molecular Imaging and Biology Pub Date : 2024-11-04 DOI:10.1007/s11307-024-01960-8

Tukang Peng, Zhijun Li, Jiebing Gao, Min Yang, Yifan Qiu, Jianzhong Xian, Lei Bi, Peizhen Ye, Yongshan Liu, Hongjun Jin

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引用次数: 0

Abstract

Purpose: Esophageal squamous cell carcinoma (ESCC) frequently exhibits skip metastasis to lymph nodes; however, non-invasive imaging techniques capable of directly visualizing metastatic lymph nodes (MLN) are still lacking. Although biopsy is the clinical standard method, it is invasive and poses risks to patient health. This study aims to detect MLN in an intralymphatic tumor metastasis model of ESCC using the CXCR4-targeted tracer [⁶⁴Cu]Cu-NOTA-CP01.

Procedures: The CXCR4 expression in ESCC cell lines was assessed using Western blot and immunofluorescence. An intralymphatic tumor metastasis model was established and monitored using bioluminescence imaging (BLI). Small animal PET studies and biodistribution studies were performed to evaluate the specificity of [⁶⁴Cu]Cu-NOTA-CP01 for MLN. Histopathology evaluation was employed to check for the presence of metastatic tumor cells and to assess CXCR4 expression levels in the metastatic lymph nodes.

Results: The intralymphatic tumor metastasis model was successfully established using the EC109/Luc cell line, which exhibited high CXCR4 expression, as verified by BLI. PET/CT imaging showed that the MLN uptakes in the baseline group were significantly inhibited in the blocking group. The ratios of MLN/muscle and MLN/blood were also significantly higher in the baseline group than in the blocking group. Ex vivo PET/CT imaging of MLN corroborated the in vivo data. Biodistribution studies further supported the PET imaging studies, showing rapid clearance of the tracer from the blood and major organs, with significantly higher MLN/muscle and MLN/blood ratios in the baseline group compared to the blocking group. Histopathological staining verified positive CXCR4 expression in these lymph nodes containing metastatic tumor cells.

Conclusions: Targeting CXCR4 with [⁶⁴Cu]Cu-NOTA-CP01 for PET imaging of lymph nodes metastasis represents a promising approach that warrants further investigation. These findings have the potential to enhance diagnostic and therapeutic strategies for individuals with lymph nodes metastasis of ESCC.

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利用 CXCR4 靶向示踪剂 [64Cu]Cu-NOTA-CP01 在体内检测 ESCC 的淋巴结转移。

目的：食管鳞状细胞癌（ESCC）经常出现淋巴结转移，但目前仍缺乏能够直接观察转移淋巴结（MLN）的无创成像技术。虽然活检是临床标准方法，但其具有侵入性，并对患者健康构成风险。本研究旨在利用CXCR4靶向示踪剂[64Cu]Cu-NOTA-CP01.Procedures检测ESCC淋巴内肿瘤转移模型中的MLN：采用Western印迹和免疫荧光评估ESCC细胞系中CXCR4的表达。建立淋巴内肿瘤转移模型，并使用生物发光成像（BLI）进行监测。进行了小动物 PET 研究和生物分布研究，以评估 [64Cu]Cu-NOTA-CP01 对 MLN 的特异性。组织病理学评估用于检查转移性肿瘤细胞的存在，并评估转移淋巴结中 CXCR4 的表达水平：结果：使用EC109/Luc细胞系成功建立了淋巴内肿瘤转移模型。PET/CT 成像显示，阻断组明显抑制了基线组的 MLN 摄取。基线组的 MLN/肌肉比率和 MLN/血液比率也明显高于阻断组。MLN 的体外 PET/CT 成像证实了体内数据。生物分布研究进一步支持了 PET 成像研究，显示示踪剂从血液和主要器官中迅速清除，基线组的 MLN/肌肉和 MLN/血液比率明显高于阻断组。组织病理学染色证实，在这些含有转移性肿瘤细胞的淋巴结中，CXCR4呈阳性表达：用[64Cu]Cu-NOTA-CP01靶向CXCR4进行淋巴结转移PET成像是一种很有前景的方法，值得进一步研究。这些发现有望加强对 ESCC 淋巴结转移患者的诊断和治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Imaging and Biology 医学-核医学

CiteScore

6.90

自引率

3.20%

发文量

审稿时长

3 months

期刊介绍： Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures. Some areas that are covered are: Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes. The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets. Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display. Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging. Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics. Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations. Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.