scholarly journals Applications of fluorescence-guided surgery across multiple tumor types using a near-infrared labeled EGFR antibody

2021 ◽  
Author(s):  
Quan Zhou ◽  
Nynke van den Berg ◽  
Wenying Kang ◽  
Jacqueline Pei ◽  
Naoki Nishio ◽  
...  
Keyword(s):  
Near Infrared ◽  
Fixed Tissue ◽  
Multiple Tumor ◽  
Tissue Sections ◽  
Guided Surgery ◽  
Link Type ◽  
Egfr Expression ◽  
Fluorescence Guided Surgery ◽  
Tumor Types ◽  
Egfr Antibody

Background As receptor-ligand based strategies emerge for surgical imaging, the relative importance of receptor expression in different tumor types is unknown. Near-infrared (NIR) labeled epidermal growth factor receptor (EGFR) antibody, panitumumab-IRDye800, was evaluated across three cancers to demonstrate its clinical utilities and a holistic analysis framework. Methods Thirty-one patients diagnosed with high-grade glioma (HGG, n=5, NCT03510208), head and neck squamous cell carcinoma (HNSCC, n=23, NCT02415881) or lung adenocarcinoma (LAC, n=3, NCT03582124) received systemic administration of 50 mg panitumumab-IRDye800 days prior to surgery. Intraoperative NIR laparoscopic or open-field images of the surgical field were acquired and tissue mimicking phantoms were constructed to identify optimal imaging conditions. Margin distance was correlated to fluorescence on resected specimen surface. Panitumumab-IRDye800 distribution was registered to histology in fixed tissue sections. Immunohistochemistry characterized EGFR expression. Results Intraoperative NIR imaging enhanced tumor contrast against surrounding healthy tissue by 5.2-fold, 3.4-fold and 1.4-fold in HGG, HNSCC and LAC, respectively. Imaging quality was optimal at the lowest gain possible under ambient light. Ex vivo NIR fluorescence identified 78-97% of at-risk resection margins, with 72-92% sensitivity and 67-96% specificity for tumor in fixed tissue sections. Intratumoral panitumumab-IRDye800 concentration correlated with total tumoral EGFR expression (HGG > HNSCC > LAC) and delivery barrier. Cellular EGFR expression (80%) and tumor cell density (3000 cells/mm2) was highest in HGG. Conclusions In multiple tumor types, EGFR-targeting in fluorescence-guided surgery translated to enhanced macroscopic tumor contrast and successful margin assessment despite disparate tumor cell density and heterogeneous delivery of pantimumab-IRDye800.

Unexpected Binding of Tozuleristide “Tumor Paint” to Cerebral Vascular Malformations: A Potentially Novel Application of Fluorescence-Guided Surgery

Neurosurgery ◽  
2021 ◽  
Author(s):  
Andrew J Kobets ◽  
David Nauen ◽  
Amy Lee ◽  
Alan R Cohen
Keyword(s):  
Near Infrared ◽  
Vascular Malformations ◽  
Cns Tumors ◽  
Matrix Metalloproteinase 2 ◽  
Cerebrovascular Lesions ◽  
Cavernous Malformations ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
Cerebral Vascular Malformations ◽  
Cerebral Vascular

Abstract BACKGROUND Fluorescence-guided surgery (FGS) is under investigation as a means to improve the extent of resection for primary central nervous system (CNS) tumors. Tozuleristide, known also as “Tumor Paint,” is an investigational tumor-targeting agent covalently conjugated to a derivative of the fluorescent dye indocyanine green. OBJECTIVE To report the finding of avid intraoperative fluorescence of tozuleristide on cerebral vascular malformations. METHODS Our institution is participating in a phase 2/3 study of intraoperative near-infrared fluorescence detection of pediatric primary CNS tumors in patients receiving intravenous tozuleristide and imaged with the Canvas system. Our site enrolled 2 patients with intracranial lesions, suspected preoperatively of possibly being gliomas that proved to be cavernous vascular malformations after resection. RESULTS Each lesion had a dark blue mulberry appearance and each fluoresced avidly with tozuleristide. Each was completely resected, and the patients recovered without deficit. Pathological assessment showed cavernous angioma for both cases. Tozuleristide fluorescence is postulated to result from binding to matrix metalloproteinase-2 and annexin A2, and literature review demonstrates expression of both these ligands on multiple cerebrovascular lesions, including cavernous malformations. CONCLUSION This finding deserves further investigation to determine if tozuleristide “Tumor Paint” may have a wider role in the identification of non-neoplastic intracranial pathologies.

scholarly journals SGM-101: An innovative near-infrared dye-antibody conjugate that targets CEA for fluorescence-guided surgery

2017 ◽  
Vol 26 (2) ◽  
pp. 153-162 ◽  
Author(s):  
Marian Gutowski ◽  
Bérénice Framery ◽  
Martin C. Boonstra ◽  
Véronique Garambois ◽  
François Quenet ◽  
...  
Keyword(s):  
Near Infrared ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
Antibody Conjugate ◽  
Near Infrared Dye

RNAScope as a platform to detect IDO1 expression in tumor tissue sections.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 116-116 ◽  
Author(s):  
Michael Pratta
Keyword(s):  
Western Blot ◽  
Hela Cell ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Tumor Tissue ◽  
Activity Level ◽  
Multiple Tumor ◽  
Tissue Sections ◽  
Ido1 Expression ◽  
Tumor Types

116 RNAScope is a sensitive, specific platform to detect IDO1 expression in tumor tissue sections. M Pratta, M Rupar, P Waeltz, T Burn, G Hollis, M Covington, M Smith, and R Newton. Incyte Corp. Wilm. DE. Background: Indoleamine 2,3-Dioxygenase 1 (IDO1) catalyzes the primary and rate-limiting step in tryptophan catabolism to generate N-formyl-kynurenine (Kyn). Through a combination of local depletion of tryptophan and an increase in Kyn concentrations, IDO-1 activity can result in the suppression of antitumor immune responses. Because IDO-1 inhibitors are now in the clinic for treatment of multiple tumor types, immunohistological approaches are employed to demonstrate IDO1 expression in tumor biopsies. However, using a commercially available antibody to detect IDO1 by immunohistochemistry (IHC), the level of sensitivity was inadequate. Methods: In order to improve the sensitivity of IDO1 detection, we evaluated in situ hybridization (ISH) using RNAScope technology and digital quantitation by HALO analysis in collaboration with Advanced Cell Diagnostics (ACD). The technology was cross-validated using IDO1 qRT-PCR, Western blot, and activity analysis and compared with standard IHC. We initially evaluated IDO1 expression in HeLa cells stimulated with various concentrations of IFNγ, and then extended the observations using tissue sections from multiple tumor types. Results: In the HeLa cell model, IFNγ induced a time- and concentration-dependent increase of IDO1 at the mRNA, protein, and activity level. Although IDO1 was successfully detected in the HeLa cell samples by IHC, comparison of the platforms indicated IFNγ EC50 values were in strong agreement between RNAScope (193.8 pg/ml) and Western blot analysis (170.8 pg/ml), but was much higher by IHC analysis (2206 pg/ml). A strong positive correlation (*p < 0.0001) between RNAScope and Western blot analysis was observed, suggesting a highly coordinated induction of IDO1 by IFNγ at both the mRNA and protein levels. FFPE tumor tissue from melanoma, HNSCC, bladder, renal, ovarian, and lung cancers visualized by RNAScope all show varying levels of IDO1 expression. Conclusions: These data support the use of RNAScope for the analysis of IDO1 expression in clinical trials.

scholarly journals Comprehensive Review of Fluorescence Applications in Gynecology

2021 ◽  
Vol 10 (19) ◽  
pp. 4387
Author(s):  
Joanna Polom ◽  
Leszek Kalinowski ◽  
Michele Diana ◽  
Manish Chand ◽  
Carmela Caballero ◽  
...  
Keyword(s):  
Cancer Detection ◽  
Near Infrared ◽  
Infrared Imaging ◽  
Safety Issues ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
Margin Detection ◽  
New Applications ◽  
Improve Patient

Since the introduction of indocyanine green (ICG) as a fluorophore in near-infrared imaging, fluorescence visualization has become an essential tool in many fields of surgery. In the field of gynecology, recent new applications have been proposed and found their place in clinical practice. Different applications in gynecology were investigated, subcategorized, and overviewed concerning surgical applications and available dyes. Specific applications in which fluorescence-guided surgery was implemented in gynecology are described in this manuscript—namely, sentinel node biopsy, mesometrium visualization, angiography of different organs, safety issues in pregnant women, ureters visualization, detection of peritoneal metastases, targeted fluorophores for cancer detection, fluorescent contamination hysterectomy, lymphography for lower limb lymphedema prevention, tumor margin detection, endometriosis, and metastases mapping. With evolving technology, further innovative research on the new applications of fluorescence visualization in cancer surgery may help to establish these techniques as standards of high-quality surgery in gynecology. However, more investigations are necessary in order to assess if these innovative tools can also be effective to improve patient outcomes and quality of life in different gynecologic malignancies.

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

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 984 ◽  
Author(s):  
Dmitry M. Polikarpov ◽  
Douglas H. Campbell ◽  
Lucinda S. McRobb ◽  
Jiehua Wu ◽  
Maria E. Lund ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Near Infrared ◽  
Ex Vivo ◽  
Extent Of Resection ◽  
Fluorescent Imaging ◽  
Control Group ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
Specific Accumulation

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.

scholarly journals EpCAM as multi-tumour target for near-infrared fluorescence guided surgery

BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
P. B. A. A. van Driel ◽  
M. C. Boonstra ◽  
H. A. J. M. Prevoo ◽  
M. van de Giessen ◽  
T. J. A. Snoeks ◽  
...  
Keyword(s):  
Near Infrared ◽  
Near Infrared Fluorescence ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
Tumour Target

scholarly journals Response to: “timing of administration of indocyanine green for fluorescence-guided surgery in pancreatic cancer: response to Shirakawa et al.”

BMC Surgery ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Sachiyo Shirakawa ◽  
Hirochika Toyama ◽  
Masahiro Kido ◽  
Takumi Fukumoto
Keyword(s):  
Pancreatic Cancer ◽  
Indocyanine Green ◽  
Hepatic Metastasis ◽  
Peritoneal Metastasis ◽  
Near Infrared ◽  
Staging Laparoscopy ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
Near Infrared Fluorescence Imaging ◽  
White Light Imaging

Abstract This is the response article to correspondence article received for our published article in BMC surgery titled “A prospective single-center protocol for using near-infrared fluorescence imaging with indocyanine green during staging laparoscopy to detect small metastasis from pancreatic cancer”. Peter L. Labib, MBChB pointed out the necessity to administer indocyanine green intravenously in separate timing for detection of metastasis in liver and peritoneum. Preoperative injection is suitable to detect hepatic metastasis and intraoperative injection is reported to be well suited to detect peritoneal metastasis. However, we could not find the usefulness of intraoperative injection of indocyanine green for detecting peritoneal metastasis in cases with staging laparoscopy prior to this study. We employed this study protocol with only preoperative injection of indocyanine green to simplify the procedure with consideration of probably more frequent cases of hepatic metastasis that is difficult to detect with white-light imaging than those of peritoneal metastasis.

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