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多模态 CEA 靶向荧光和放射性核素引导的结直肠来源腹膜转移细胞减灭术。

Multimodal CEA-targeted fluorescence and radioguided cytoreductive surgery for peritoneal metastases of colorectal origin.

机构信息

Department of Medical Imaging, Nuclear medicine, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.

Department of Surgery Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.

出版信息

Nat Commun. 2022 May 12;13(1):2621. doi: 10.1038/s41467-022-29630-9.


DOI:10.1038/s41467-022-29630-9
PMID:35551444
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9098887/
Abstract

In patients with colorectal peritoneal metastases scheduled for cytoreductive surgery, accurate preoperative estimation of tumor burden and subsequent intraoperative detection of all tumor deposits remains challenging. In this study (ClinicalTrials.gov NCT03699332) we describe the results of a phase I clinical trial evaluating [In]In-DOTA-labetuzumab-IRDye800CW, a dual-labeled anti-carcinoembryonic antigen (anti-CEA) antibody conjugate that enables both preoperative imaging and intraoperative radioguidance and fluorescence imaging. Primary study outcomes are safety and feasibility of this multimodal imaging approach. Secondary outcomes are determination of the optimal dose, correlation between tracer uptake and histopathology and effects on clinical strategy. Administration of [In]In-DOTA-labetuzumab-IRDye800CW is well-tolerated and enables sensitive pre- and intraoperative imaging in patients who receive 10 or 50 mg of the tracer. Preoperative imaging revealed previously undetected lymph node metastases in one patient, and intraoperative fluorescence imaging revealed four previously undetected metastases in two patients. Alteration of clinical strategy based on multimodal imaging occurred in three patients. Thus, multimodal image-guided surgery after administration of this dual-labeled tracer is a promising approach that may aid in decision making before and during cytoreductive surgical procedures.

摘要

在计划接受细胞减灭手术的结直肠腹膜转移患者中,准确预测肿瘤负荷和术中检测所有肿瘤沉积物仍然具有挑战性。在这项研究(ClinicalTrials.gov NCT03699332)中,我们描述了评估 [In]In-DOTA-labetuzumab-IRDye800CW 的 I 期临床试验结果,这是一种双标记抗癌胚抗原(anti-CEA)抗体偶联物,可实现术前成像和术中放射引导以及荧光成像。主要研究结果是这种多模态成像方法的安全性和可行性。次要结果是确定最佳剂量、示踪剂摄取与组织病理学的相关性以及对临床策略的影响。[In]In-DOTA-labetuzumab-IRDye800CW 的给药耐受良好,接受 10 或 50mg 示踪剂的患者可进行敏感的术前和术中成像。术前成像在一名患者中发现了先前未检测到的淋巴结转移,术中荧光成像在两名患者中发现了四个先前未检测到的转移。根据多模态成像改变临床策略的患者有三人。因此,该双标记示踪剂给药后的多模态图像引导手术是一种很有前途的方法,可能有助于在细胞减灭手术前和手术期间做出决策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/9098887/a40057c23b05/41467_2022_29630_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/9098887/411a8e844ca4/41467_2022_29630_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/9098887/7bd86ad866d9/41467_2022_29630_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/9098887/9b5890a09922/41467_2022_29630_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/9098887/a40057c23b05/41467_2022_29630_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/9098887/411a8e844ca4/41467_2022_29630_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/9098887/7bd86ad866d9/41467_2022_29630_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/9098887/9b5890a09922/41467_2022_29630_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/9098887/a40057c23b05/41467_2022_29630_Fig4_HTML.jpg

相似文献

[1]
Multimodal CEA-targeted fluorescence and radioguided cytoreductive surgery for peritoneal metastases of colorectal origin.

Nat Commun. 2022-5-12

[2]
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[3]
Safety and effectiveness of SGM-101, a fluorescent antibody targeting carcinoembryonic antigen, for intraoperative detection of colorectal cancer: a dose-escalation pilot study.

Lancet Gastroenterol Hepatol. 2018-1-30

[4]
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J Surg Oncol. 2018-8

[5]
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Br J Surg. 2020-1-21

[6]
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Clin Cancer Res. 2020-11-15

[7]
Fluorescence Imaging After Indocyanine Green Injection for Detection of Peritoneal Metastases in Patients Undergoing Cytoreductive Surgery for Peritoneal Carcinomatosis From Colorectal Cancer: A Pilot Study.

Ann Surg. 2016-12

[8]
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Eur J Surg Oncol. 2021-3

[9]
Detection of Micrometastases Using SPECT/Fluorescence Dual-Modality Imaging in a CEA-Expressing Tumor Model.

J Nucl Med. 2017-5

[10]
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Surg Oncol. 2017-6

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[3]
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[4]
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[5]
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[6]
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J Gastrointest Cancer. 2025-1-23

[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
The Accuracy of the Surgical Peritoneal Cancer Index in Patients with Peritoneal Metastases of Colorectal Cancer.

Dig Surg. 2021

[2]
Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial.

Lancet Oncol. 2021-2

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Co-administered antibody improves penetration of antibody-dye conjugate into human cancers with implications for antibody-drug conjugates.

Nat Commun. 2020-11-9

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Cancers (Basel). 2020-4-17

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Identifying Biomarkers in Lymph Node Metastases of Esophageal Adenocarcinoma for Tumor-Targeted Imaging.

Mol Diagn Ther. 2020-4

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Abdom Radiol (NY). 2020-2

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Diagnostic Laparoscopy as a Selection Tool for Patients with Colorectal Peritoneal Metastases to Prevent a Non-therapeutic Laparotomy During Cytoreductive Surgery.

Ann Surg Oncol. 2019-10-22

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Meta-analysis of prognostic factors for patients with colorectal peritoneal metastasis undergoing cytoreductive surgery and heated intraperitoneal chemotherapy.

BJS Open. 2019-6-27

[9]
Roadmap for the Development and Clinical Translation of Optical Tracers Cetuximab-800CW and Trastuzumab-800CW.

J Nucl Med. 2019-1-10

[10]
Clinical lymph node staging in colorectal cancer; a flip of the coin?

Eur J Surg Oncol. 2018-4-17

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