دورية أكاديمية
أعرض في EDS

Carcinoembryonic Antigen-Related Cell Adhesion Molecule Type 5 Receptor-Targeted Fluorescent Intraoperative Molecular Imaging Tracer for Lung Cancer: A Nonrandomized Controlled Trial.

التفاصيل البيبلوغرافية
العنوان: Carcinoembryonic Antigen-Related Cell Adhesion Molecule Type 5 Receptor-Targeted Fluorescent Intraoperative Molecular Imaging Tracer for Lung Cancer: A Nonrandomized Controlled Trial.
المؤلفون: Azari F; Department of Thoracic Surgery, University of Pennsylvania, Philadelphia., Meijer RPJ; Centre for Human Drug Research, Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands., Kennedy GT; Department of Thoracic Surgery, University of Pennsylvania, Philadelphia., Hanna A; Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia., Chang A; Department of Thoracic Surgery, University of Pennsylvania, Philadelphia., Nadeem B; Department of Thoracic Surgery, University of Pennsylvania, Philadelphia., Din A; Department of Thoracic Surgery, University of Pennsylvania, Philadelphia., Pèlegrin A; SurgiMab, Montpellier, France.; Institute of Cancer Research of Montpellier, University of Montpellier, Montpellier, France., Framery B; SurgiMab, Montpellier, France., Cailler F; SurgiMab, Montpellier, France., Sullivan NT; Department of Thoracic Surgery, University of Pennsylvania, Philadelphia., Kucharczuk J; Department of Thoracic Surgery, University of Pennsylvania, Philadelphia., Martin LW; Department of Thoracic Surgery, University of Virginia School of Medicine, Charlottesville., Vahrmeijer AL; Centre for Human Drug Research, Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands., Singhal S; Department of Thoracic Surgery, University of Pennsylvania, Philadelphia.
المصدر: JAMA network open [JAMA Netw Open] 2023 Jan 03; Vol. 6 (1), pp. e2252885. Date of Electronic Publication: 2023 Jan 03.
نوع المنشور: Clinical Trial, Phase I; Controlled Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Medical Association Country of Publication: United States NLM ID: 101729235 Publication Model: Electronic Cited Medium: Internet ISSN: 2574-3805 (Electronic) Linking ISSN: 25743805 NLM ISO Abbreviation: JAMA Netw Open Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Chicago, IL : American Medical Association, [2018]-
مواضيع طبية MeSH: Lung Neoplasms*/diagnostic imaging , Lung Neoplasms*/surgery , Multiple Pulmonary Nodules*, Aged ; Female ; Humans ; Male ; Carcinoembryonic Antigen ; Fluorescent Dyes ; Molecular Imaging/methods ; Middle Aged
مستخلص: Importance: Localization of subcentimeter ground glass opacities during minimally invasive thoracoscopic lung cancer resections is a significant challenge in thoracic oncology. Intraoperative molecular imaging has emerged as a potential solution, but the availability of suitable fluorescence agents is a limiting factor.
Objective: To evaluate the suitability of SGM-101, a carcinoembryonic antigen-related cell adhesion molecule type 5 (CEACAM5) receptor-targeted near-infrared fluorochrome, for molecular imaging-guided lung cancer resections, because glycoprotein is expressed in more than 80% of adenocarcinomas.
Design, Setting, and Participants: For this nonrandomized, proof-of-principal, phase 1 controlled trial, patients were divided into 2 groups between August 1, 2020, and January 31, 2022. Patients with known CEACAM5-positive gastrointestinal tumors suggestive of lung metastasis were selected as proof-of-principle positive controls. The investigative group included patients with lung nodules suggestive of primary lung malignant neoplasms. Patients 18 years or older without significant comorbidities that precluded surgical exploration with suspicious pulmonary nodules requiring surgical biopsy were included in the study.
Interventions: SGM-101 (10 mg) was infused up to 5 days before index operation, and pulmonary nodules were imaged using a near-infrared camera system with a dedicated thoracoscope.
Main Outcomes and Measures: SGM-101 localization to pulmonary nodules and its correlation with CEACAM5 glycoprotein expression by the tumor as quantified by tumor and normal pulmonary parenchymal fluorescence.
Results: Ten patients (5 per group; 5 male and 5 female; median [IQR] age, 66 [58-69] years) with 14 total lesions (median [range] lesion size, 0.91 [0.90-2.00] cm) were enrolled in the study. In the control group of 4 patients (1 patient did not undergo surgical resection because of abnormal preoperative cardiac clearance findings that were not deemed related to SGM-101 infusion), the mean (SD) lesion size was 1.33 (0.48) cm, 2 patients had elevated serum CEA markers, and 2 patients had normal serum CEA levels. Of the 4 patients who underwent surgical intervention, those with 2+ and 3+ tissue CEACAM5 expression had excellent tumor fluorescence, with a mean (SD) tumor to background ratio of 3.11 (0.45). In the patient cohort, the mean (SD) lesion size was 0.68 (0.22) cm, and no elevations in serum CEA levels were found. Lack of SGM-101 fluorescence was associated with benign lesions and with lack of CEACAM5 staining.
Conclusions and Relevance: This in-human proof-of-principle nonrandomized controlled trial demonstrated SGM-101 localization to CEACAM5-positive tumors with the detection of real-time near-infrared fluorescence in situ, ex vivo, and by immunofluorescence microscopy. These findings suggest that SGM-101 is a safe, receptor-specific, and feasible intraoperative molecular imaging fluorochrome that should be further evaluated in randomized clinical trials.
Trial Registration: ClinicalTrials.gov identifier: NCT04315467.
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معلومات مُعتمدة: F32 CA254210 United States CA NCI NIH HHS; P01 CA254859 United States CA NCI NIH HHS; T32 CA009140 United States CA NCI NIH HHS; T32 CA251063 United States CA NCI NIH HHS
سلسلة جزيئية: ClinicalTrials.gov NCT04315467
المشرفين على المادة: 0 (Carcinoembryonic Antigen)
0 (Fluorescent Dyes)
0 (CEACAM5 protein, human)
تواريخ الأحداث: Date Created: 20230127 Date Completed: 20230203 Latest Revision: 20240104
رمز التحديث: 20240104
مُعرف محوري في PubMed: PMC10292762
DOI: 10.1001/jamanetworkopen.2022.52885
PMID: 36705924
قاعدة البيانات: MEDLINE
الوصف
تدمد:2574-3805
DOI:10.1001/jamanetworkopen.2022.52885