Single-Dose Intravenous Toxicity Study of IRDye 800CW in Sprague-Dawley Rats

Marshall, Milton V.; Draney, Daniel R.; Sevick‐Muraca, Eva M.; Olive, D. Michael

doi:10.1007/s11307-010-0317-x

Cited by 207 publications

(180 citation statements)

References 28 publications

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“…IRDye 800CW is a NIR fluorophore with optimal characteristics for clinical use, allowing binding to antibodies when used in its N-hydroxysuccinimide (NHS) ester form. A preclinical toxicity study with IRDye 800CW carboxylate showed no toxicity in doses of up to 20 mg/kg intravenously or intradermally (16).…”

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confidence: 99%

Intraoperative Near-Infrared Fluorescence Tumor Imaging with Vascular Endothelial Growth Factor and Human Epidermal Growth Factor Receptor 2 Targeting Antibodies

Scheltinga¹,

Dam²,

Nagengast³

et al. 2011

J Nucl Med

177

141

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Fluorescence imaging is currently attracting much interest as a method for intraoperative tumor detection, but most current tracers lack tumor specificity. Therefore, this technique can be further improved by tumor-specific detection. With tumortargeted antibodies bound to a radioactive label, tumor-specific SPECT or PET is feasible in the clinical setting. The aim of the present study was to apply antibody-based tumor detection to intraoperative optical imaging, using preclinical in vivo mouse models. Methods: Anti-vascular endothelial growth factor (VEGF) antibody bevacizumab and anti-human epidermal growth factor receptor (HER) 2 antibody trastuzumab were labeled with the near-infrared (NIR) fluorescence dye IRDye 800CW. Tumor uptake of the fluorescent tracers and their 89 Zr-labeled radioactive counterparts for PET was determined in human xenograft-bearing athymic mice during 1 wk after tracer injection, followed by ex vivo biodistribution and pathologic examination. Intraoperative imaging of fluorescent VEGF-or HER2-positive tumor lesions was performed in subcutaneous tumors and in intraperitoneal dissemination tumor models. Results: Tumorto-background ratios, with fluorescent imaging, were 1.93 6 0.40 for bevacizumab and 2.92 6 0.29 for trastuzumab on day 6 after tracer injection. Real-time intraoperative imaging detected tumor lesions at even the submillimeter level in intraperitoneal dissemination tumor models. These results were supported by standard histology, immunohistochemistry, and fluorescence microscopy analyses. Conclusion: NIR fluorescence-labeled antibodies targeting VEGF or HER2 can be used for highly specific and sensitive detection of tumor lesions in vivo. These preclinical findings encourage future clinical studies with NIR fluorescence-labeled tumor-specific antibodies for intraoperative-guided surgery in cancer patients.

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mentioning

confidence: 99%

Intraoperative Near-Infrared Fluorescence Tumor Imaging with Vascular Endothelial Growth Factor and Human Epidermal Growth Factor Receptor 2 Targeting Antibodies

Scheltinga¹,

Dam²,

Nagengast³

et al. 2011

J Nucl Med

177

141

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“…A major shortcoming of ICG, however, is that it lacks a reactive functional group and therefore, cannot be used to label targeting agents. 33 Because most cancers are heterogeneous in nature and may exhibit different expression patterns, it may be that combinations of labeled tumor-targeting agents are necessary to completely visualize cancers in the surgical bed. Variations in tumor antigens, both between tumors and within a tumor, could potentially influence fluorescence intensity.…”

Section: Discussionmentioning

confidence: 99%

Identification of the optimal therapeutic antibody for fluorescent imaging of cutaneous squamous cell carcinoma

Day

Beck

Heath

et al. 2013

Cancer Biology & Therapy

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“…This NIR fluorescent dye underwent extensive toxicity testing and is a good-manufacturing-practice-compliant compound, registered at the U.S. Food and Drug Administration (16,17).…”

Section: Fluorescent Labeling Of Monoclonal Antibodiesmentioning

confidence: 99%

Molecular Fluorescence Endoscopy Targeting Vascular Endothelial Growth Factor A for Improved Colorectal Polyp Detection

et al. 2015

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Small and flat adenomas are known to carry a high miss-rate during standard white-light endoscopy. Increased detection rate may be achieved by molecular fluorescence endoscopy with targeted nearinfrared (NIR) fluorescent tracers. The aim of this study was to validate vascular endothelial growth factor A (VEGF-A) and epidermal growth factor receptor (EGFR)-targeted fluorescent tracers during ex vivo colonoscopy with an NIR endoscopy platform. Methods: VEGF-A and EGFR expression was determined by immunohistochemistry on a large subset of human colorectal tissue samples-48 sessile serrated adenomas/polyps, 70 sporadic high-grade dysplastic adenomas, and 19 hyperplastic polyps-and tissue derived from patients with Lynch syndrome-78 low-grade dysplastic adenomas, 57 high-grade dysplastic adenomas, and 31 colon cancer samples. To perform an ex vivo colonoscopy procedure, 14 mice with small intraperitoneal EGFR-positive HCT116 luc tumors received intravenous bevacizumab-800CW (anti-VEGF-A), cetuximab-800CW (anti-EGFR), control tracer IgG-800CW, or sodium chloride. Three days later, 8 resected HCT116 luc tumors (2-5 mm) were stitched into 1 freshly resected human colon specimen and followed by an ex vivo molecular fluorescence colonoscopy procedure. Results: Immunohistochemistry showed high VEGF-A expression in 79%-96% and high EGFR expression in 51%-69% of the colorectal lesions. Both targets were significantly overexpressed in the colorectal lesions, compared with the adjacent normal colon crypts. During ex vivo molecular fluorescence endoscopy, all tumors could clearly be delineated for both bevacizumab-800CW and cetuximab-800CW tracers. Specific tumor uptake was confirmed with fluorescent microscopy showing, respectively, stromal and cell membrane fluorescence. Conclusion: VEGF-A is a promising target for molecular fluorescence endoscopy because it showed a high protein expression, especially in sessile serrated adenomas/polyps and Lynch syndrome. We demonstrated the feasibility to visualize small tumors in real time during colonoscopy using a NIR fluorescence endoscopy platform, providing the endoscopist a wide-field redflag technique for adenoma detection. Clinical studies are currently being performed in order to provide in-human evaluation of our approach.

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Single-Dose Intravenous Toxicity Study of IRDye 800CW in Sprague-Dawley Rats

Cited by 207 publications

References 28 publications

Intraoperative Near-Infrared Fluorescence Tumor Imaging with Vascular Endothelial Growth Factor and Human Epidermal Growth Factor Receptor 2 Targeting Antibodies

Intraoperative Near-Infrared Fluorescence Tumor Imaging with Vascular Endothelial Growth Factor and Human Epidermal Growth Factor Receptor 2 Targeting Antibodies

Identification of the optimal therapeutic antibody for fluorescent imaging of cutaneous squamous cell carcinoma

Molecular Fluorescence Endoscopy Targeting Vascular Endothelial Growth Factor A for Improved Colorectal Polyp Detection

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