Sensitivity and Specificity of Cetuximab-IRDye800CW to Identify Regional Metastatic Disease in Head and Neck Cancer

Rosenthal, Eben L.; Moore, Lindsay; Tipirneni, Kiranya E.; Boer, Esther de; Stevens, Todd M.; Hartman, Yolanda E.; Carroll, William R.; Zinn, Kurt R.; Warram, Jason M.

doi:10.1158/1078-0432.ccr-16-2968

Cited by 108 publications

(88 citation statements)

References 24 publications

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“…Moreover, we have demonstrated that a higher dose of cetuximab-IRDye800 leads to improved delineation between tumor and normal tissue, which is consistent with the aforementioned study in squamous cell carcinoma (SCC) with this agent [9], where increased doses led to higher signals in the primary tumor. However, in the case of SCC, the dose limiting factor was based on false-positive results in lymph nodes at higher doses [16]. The increased sensitivity and specificity seen in the high dose as compared to the low dose patient in the current study suggests that false-positivity is less of a concern in glioblastoma resection, though our small sample size warrants further study.…”

Section: Discussionmentioning

confidence: 75%

“…As this is the first in-human study using this technology, it was important to establish a baseline of non-specific fluorescence uptake in non-tumor tissue. This methodology has previously been demonstrated in prior publications in a variety of tumor types [16, 17]. A histologically proven tumor specimen that was fluorescent was considered a true-positive; a histologically normal specimen that was fluorescent was a false-positive; a histologically normal specimen that was non-fluorescent was a true-negative; and a histologically positive tumor that was non-fluorescent was a false-negative.…”

Section: Methodsmentioning

confidence: 93%

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

et al. 2018

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Introduction Maximizing extent of surgical resection with the least morbidity remains critical for survival in glioblastoma patients, and we hypothesize that it can be improved by enhancements in intraoperative tumor detection. In a clinical study, we determined if therapeutic antibodies could be repurposed for intraoperative imaging during resection. Methods Fluorescently labeled cetuximab-IRDye800 was systemically administered to three patients 2 days prior to surgery. Near-infrared fluorescence imaging of tumor and histologically negative peri-tumoral tissue was performed intraoperatively and ex vivo. Fluorescence was measured as mean fluorescence intensity (MFI), and tumor-to-background ratios (TBRs) were calculated by comparing MFIs of tumor and histologically uninvolved tissue. Results The mean TBR was significantly higher in tumor tissue of contrast-enhancing (CE) tumors on preoperative imaging (4.0 ± 0.5) compared to non-CE tumors (1.2 ± 0.3; p = 0.02). The TBR was higher at a 100 mg dose than at 50 mg (4.3 vs. 3.6). The smallest detectable tumor volume in a closed-field setting was 70 mg with 50 mg of dye and 10 mg with 100 mg. On sections of paraffin embedded tissues, fluorescence positively correlated with histological evidence of tumor. Sensitivity and specificity of tumor fluorescence for viable tumor detection was calculated and fluorescence was found to be highly sensitive (73.0% for 50 mg dose, 98.2% for 100 mg dose) and specific (66.3% for 50 mg dose, 69.8% for 100 mg dose) for viable tumor tissue in CE tumors while normal peri-tumoral tissue showed minimal fluorescence. Conclusion This first-in-human study demonstrates the feasibility and safety of antibody based imaging for CE glioblastomas.

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Section: Discussionmentioning

confidence: 75%

Section: Methodsmentioning

confidence: 93%

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

et al. 2018

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“…We hypothesize that this is caused by lymphatic drainage of excess antibody to the primary nodal basin, which is similar to findings with cetuximab-IRDye800 in head and neck cancer. 22 We have shown that this technique can guide tumor-bearing LN detection and removal when used at the optimal dose, which can be beneficial in patients with tumor-bearing LN in the first-echelon (N1). 23 Therefore, the optimal dose Cetuximab-IRDye800 established in this study is 50 mg, with a loading dose of 100 mg cetuximab.…”

Section: Discussionmentioning

confidence: 99%

Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging

et al. 2018

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Background Operative management of pancreatic ductal adenocarcinoma (PDAC) is complicated by several key decisions during the procedure. Identification of metastatic disease at the outset and, when none is found, complete (R0) resection of primary tumor are key to optimizing clinical outcomes. The use of tumor-targeted molecular imaging, based on photoacoustic and fluorescence optical imaging, can provide crucial information to the surgeon. The first-in-human use of multimodality molecular imaging for intraoperative detection of pancreatic cancer is reported using cetuximab-IRDye800, a near-infrared fluorescent agent that binds to epidermal growth factor receptor. Methods A dose-escalation study was performed to assess safety and feasibility of targeting and identifying PDAC in a tumor-specific manner using cetuximab-IRDye800 in patients undergoing surgical resection for pancreatic cancer. Patients received a loading dose of 100 mg of unlabeled cetuximab before infusion of cetuximab-IRDye800 (50 mg or 100 mg). Multi-instrument fluorescence imaging was performed throughout the surgery in addition to fluorescence and photoacoustic imaging ex vivo. Results Seven patients with resectable pancreatic masses suspected to be PDAC were enrolled in this study. Fluorescence imaging successfully identified tumor with a significantly higher mean fluorescence intensity in the tumor (0.09 ± 0.06) versus surrounding normal pancreatic tissue (0.02 ± 0.01), and pancreatitis (0.04 ± 0.01; p < 0.001), with a sensitivity of 96.1% and specificity of 67.0%. The mean photoacoustic signal in the tumor site was 3.7-fold higher than surrounding tissue. Conclusions The safety and feasibilty of intraoperative, tumor-specific detection of PDAC using cetuximab-IRDye800 with multimodal molecular imaging of the primary tumor and metastases was demonstrated.

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“…Fluorescence‐guided surgery (FGS) is a rapidly growing field. 5‐Aminolevulinic acid/protoporphyrin IX was recently approved for clinical use, and numerous protein‐targeted and activatable fluorophores are in preclinical and phase 0/1 clinical trials . We have developed and begun testing ABY‐029, an IRDye 800CW‐labeled anti‐epidermal growth factor receptor (EGFR) Affibody ® molecule.…”

Section: Introductionmentioning

confidence: 99%

Preclinical imaging of epidermal growth factor receptor with ABY‐029 in soft‐tissue sarcoma for fluorescence‐guided surgery and tumor detection

Samkoe

Sardar

Bates

et al. 2019

Journal of Surgical Oncology

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Background and Objectives Fluorescence‐guided surgery using epidermal growth factor receptor (EGFR) targeting has been performed successfully in clinical trials using a variety of fluorescent agents. We investigate ABY‐029 (anti‐EGFR Affibody® molecule labeled with IRDye 800CW) compared with a small‐molecule perfusion agent, IRDye 700DX carboxylate, in a panel of soft‐tissue sarcomas with varying levels of EGFR expression and vascularization. Methods Five xenograft soft‐tissue sarcoma cell lines were implanted into immunosuppressed mice. ABY‐029 and IRDye 700DX were each administered at 4.98 μM. Fluorescence from in vivo and ex vivo (fresh and formalin‐fixed) fixed tissues were compared. The performance of three fluorescence imaging systems was assessed for ex vivo tissues. Results ABY‐029 is retained longer within tumor tissue and achieves higher tumor‐to‐background ratios both in vivo and ex vivo than IRDye 700DX. ABY‐029 fluorescence is less susceptible to formalin fixation than IRDye 700DX, but both agents have disproportional signal loss in a variety of tissues. The Pearl Impulse provides the highest contrast‐to‐noise ratio, but all systems have individual advantages. Conclusions ABY‐029 demonstrates promise to assist in wide local excision of soft‐tissue sarcomas. Further clinical evaluation of in situ or freshly excised ex vivo tissues using fluorescence imaging systems is warranted.

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Sensitivity and Specificity of Cetuximab-IRDye800CW to Identify Regional Metastatic Disease in Head and Neck Cancer

Cited by 108 publications

References 24 publications

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

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

Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging

Preclinical imaging of epidermal growth factor receptor with ABY‐029 in soft‐tissue sarcoma for fluorescence‐guided surgery and tumor detection

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