First-in-human intraoperative near-infrared fluorescence imaging of glioblastoma using cetuximab-IRDye800

Miller, Sarah E.; Tummers, Willemieke S.; Teraphongphom, Nutte; Berg, Nynke S. van den; Hasan, Alifia; Ertsey, Robert; Nagpal, Seema; Recht, Lawrence D.; Plowey, Edward D.; Vogel, Hannes; Harsh, Griffith R.; Grant, Gerald A.; Li, Gordon

doi:10.1007/s11060-018-2854-0

Cited by 110 publications

(113 citation statements)

References 22 publications

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“…Targeted NIR fluorescence imaging has already been studied in several clinical trials for colorectal, head and neck, pancreatic and renal cancer and has shown its potential and added value in intraoperative decision making 21,25,[31][32][33] . As a result of these trials, a variety of suitable biomarkers have been identified for NIR-fluorescence guided surgery.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical selection of biomarkers for tumor-targeted image-guided surgery of myxofibrosarcoma

Gooyer

Versleijen-Jonkers²,

Hillebrandt-Roeffen³

et al. 2020

Sci Rep

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Myxofibrosarcoma(MFS) is the most common soft tissue sarcoma(STS) in elderly patients. Surgical resection remains the main treatment modality but tumor borders can be difficult to delineate with conventional clinical methods. Incomplete resections are a common problem and local recurrence remains a clinical issue. A technique that has shown great potential in improving surgical treatment of solid tumors is tumor targeted imaging and image-guided surgery with near-infrared fluorescence. To facilitate this technique, it is essential to identify a biomarker that is highly and homogenously expressed on tumor cells, while being absent on healthy non-malignant tissue. The purpose of this study was to identify suitable molecular targets for tumor-targeted imaging of myxofibrosarcoma. Ten potential molecular targets for tumor targeted imaging were investigated with immunohistochemical analysis in myxofibrosarcoma tissue (n = 34). Results were quantified according to the immunoreactive score(IRS). Moderate expression rates were found for uPAR, PDGFRa and EMA/MUC1. High expression rates of VEGF and TEM1 were seen. Strong expression was most common for TEM1 (88.2%). These results confirms that TEM1 is a suitable target for tumor-targeted imaging of myxofibrosarcoma. Keywords Image-guided surgery; Immunohistochemistry; Molecular imaging; Myxofibrosarcoma; Soft tissue sarcoma; Tumor endothelial marker 1(TEM1), Vascular endothelial growth factor (VEGF).Myxofibrosarcoma (MFS) is a histological subtype of soft tissue sarcoma (STS) formerly classified as a myxoidtype malignant fibrous histiocytoma. It has been reclassified and defined as a distinct pathological entity in the World Health Organization (WHO) criteria set in 2002 1,2 . Myxofibrosarcoma is a relatively common sarcoma in the elderly that mainly arises in the extremities 3 . Primary MFS most often presents as a subcutaneous painless, slow growing nodule, but completely infiltrative growth patterns along fascial planes without formation of an evident tumor mass have also been described 4 . The low-grade lesions have a relatively low metastatic potential but show a significant propensity for local recurrences 5-8 . These recurrences show higher-grade histology in up to 50% of all cases compared to the primary tumor 3 . Subsequently, high and intermediate grade disease exhibits a greater metastatic potential, mainly metastasizing to the lungs and lymph nodes 7,9 . Current guidelines recommend wide surgical resection combined with pre or post-operative radiotherapy as the preferred treatment 10 . Despite this strategy, positive margins after surgery occur in up to 20% of cases and reported local relapse rates range from 15 to 65% [5][6][7][8]11 .Currently clinicians rely on conventional imaging modalities such as CT and MRI to determine the location and extent of tumor burden prior to surgery. Translating these conventional imaging modalities to the surgical theatre remains challenging, forcing the surgeon to depend mainly on tactile and visual cues during the procedure. P...

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Section: Discussionmentioning

confidence: 99%

Immunohistochemical selection of biomarkers for tumor-targeted image-guided surgery of myxofibrosarcoma

Gooyer

Versleijen-Jonkers²,

Hillebrandt-Roeffen³

et al. 2020

Sci Rep

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“…défini par l'agence européenne des médicaments (EMA, European medicines agency) et la FDA (food and drug administration), n'a pas permis l'évaluation peropératoire des marges chirurgicales [25]. Sept études ont évalué le cétuximab (anti-EGFR)-IRDye800CW essentiellement dans les cancers otorhino-laryngés (ORL) (37 patients au total [26][27][28][29]) et les adénocarcinomes pancréatiques (14 patients au total [30,31]), puis dans une étude pilote de 3 patients pour le glioblastome [32]. Une fluorescence spécifique a été observée dans une majorité des cas avec des doses injectées relativement élevées en raison de l'expression de l'EGFR dans les tissus normaux.…”

Section: Revuesunclassified

Les anticorps, outils de choix pour la chirurgie guidée par fluorescence

2019

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La chirurgie guidée par fluorescence se développe en clinique depuis plusieurs années. Si l’utilisation de colorants non ciblés peut être utile dans certaines pathologies, des agents de contraste spécifiques sont indispensables en oncologie. Comme le montrent les dernières études cliniques, les anticorps monoclonaux ont toutes les caractéristiques pour jouer un rôle majeur dans ce domaine d’imagerie médicale, à condition que la cible antigénique soit pertinente.

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“…This concept was initially approached by conjugating conventional passive dyes, such as fluorescein [24] and ICG [25], to targeting molecules but then the interest shifted towards more suitable fluorescent dyes which need be well tolerated, able to produce high-contrast image, and suitable for bioconjugation [22,26,27]. One of the dyes that fulfills these criteria and has shown the most promising results in clinical trials is IRDye800CW (IR800) [11,28]. This dye has an excellent safety profile and can be visualized by existing equipment developed for widespread FDA-approved dye indocyanine green, and its conjugates with anti-EGFR antibodies have been successfully used in preclinical and clinical trials for GBM and other cancers [28][29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

Near-Infrared Molecular Imaging of Glioblastoma by Miltuximab®-IRDye800CW as a Potential Tool for Fluorescence-Guided Surgery

Polikarpov

Campbell²,

McRobb

et al. 2020

Cancers

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Glioblastoma (GBM) is one of the most aggressive tumors and its 5-year survival is approximately 5%. Fluorescence-guided surgery (FGS) improves the extent of resection and leads to better prognosis. Molecular near-infrared (NIR) imaging appears to outperform conventional FGS, however, novel molecular targets need to be identified in GBM. Proteoglycan glypican-1 (GPC-1) is believed to be such a target as it is highly expressed in GBM and is associated with poor prognosis. We hypothesize that an anti-GPC-1 antibody, Miltuximab®, conjugated with the NIR dye, IRDye800CW (IR800), can specifically accumulate in a GBM xenograft and provide high-contrast in vivo fluorescent imaging in rodents following systemic administration. Miltuximab® was conjugated with IR800 and intravenously administered to BALB/c nude mice bearing a subcutaneous U-87 GBM hind leg xenograft. Specific accumulation of Miltuximab®-IR800 in subcutaneous xenograft tumor was detected 24 h later using an in vivo fluorescence imager. The conjugate did not cause any adverse events in mice and caused strong fluorescence of the tumor with tumor-to-background ratio (TBR) reaching 10.1 ± 2.8. The average TBR over the 10-day period was 5.8 ± 0.6 in mice injected with Miltuximab®-IR800 versus 2.4 ± 0.1 for the control group injected with IgG-IR800 (p = 0.001). Ex vivo assessment of Miltuximab®-IR800 biodistribution confirmed its highly specific accumulation in the tumor. The results of this study confirm that Miltuximab®-IR800 holds promise for intraoperative fluorescence molecular imaging of GBM and warrants further studies.

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First-in-human intraoperative near-infrared fluorescence imaging of glioblastoma using cetuximab-IRDye800

Cited by 110 publications

References 22 publications

Immunohistochemical selection of biomarkers for tumor-targeted image-guided surgery of myxofibrosarcoma

Immunohistochemical selection of biomarkers for tumor-targeted image-guided surgery of myxofibrosarcoma

Les anticorps, outils de choix pour la chirurgie guidée par fluorescence

Near-Infrared Molecular Imaging of Glioblastoma by Miltuximab®-IRDye800CW as a Potential Tool for Fluorescence-Guided Surgery

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