scholarly journals Comparison of HER2-Targeted Antibodies for Fluorescence-Guided Surgery in Breast Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Solmaz AghaAmiri ◽  
Jo Simien ◽  
Alastair M. Thompson ◽  
Julie Voss ◽  
Sukhen C. Ghosh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Near Infrared ◽  
Residual Disease ◽  
Ex Vivo ◽  
Guided Surgery ◽  
Nirf Imaging ◽  
Fluorescence Guided Surgery ◽  
Imaging Results

Background. Although therapeutic advances have led to enhanced survival in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, detection of residual disease remains challenging. Here, we examine two approved anti-HER2 monoclonal antibodies (mAbs), trastuzumab and pertuzumab, as potential candidates for the development of immunoconjugates for fluorescence-guided surgery (FGS). Methods. mAbs were conjugated to the near-infrared fluorescent (NIRF) dye, IRDye800, and for quantitative in vitro assessment, to the radiometal chelator, desferrioxamine, to enable dual labeling with 89Zr. In vitro binding was evaluated in HER2-overexpressing (BT474, SKBR3) and HER2-negative (MCF7) cell lines. BT474 and MCF7 xenografts were used for in vivo and ex vivo fluorescence imaging. Results. In vitro findings demonstrated HER2-mediated binding for both fluorescent immunoconjugates and were in agreement with radioligand assays using dual-labeled immunoconjugates. In vivo and ex vivo studies showed preferential accumulation of the fluorescently-labeled mAbs in tumors and similar tumor-to-background ratios. In vivo HER2 specificity was confirmed by immunohistochemical staining of resected tumors and normal tissues. Conclusions. We showed for the first time that fluorescent trastuzumab and pertuzumab immunoconjugates have similar NIRF imaging performance and demonstrated the possibility of performing HER2-targeted FGS with agents that possess distinct epitope specificity.

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.

Abstract 17216: Intracoronary Dual-modal OCT/NIRF Structural-Molecular Imaging with a Clinical Dose of Indocyanine Green (ICG) for Detection of High-risk Coronary Plaques in Diabetic Swine Model

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sunwon Kim ◽  
Min Woo Lee ◽  
Han Saem Cho ◽  
Joon Woo Song ◽  
Sunki Lee ◽  
...  
Keyword(s):  
High Risk ◽  
Near Infrared ◽  
Ex Vivo ◽  
Swine Model ◽  
Fully Integrated ◽  
Coronary Syndrome ◽  
Fibrous Cap ◽  
Nirf Imaging

Background: Acute coronary syndrome is frequently caused by rupture of macrophage abundant plaques with a large lipid-rich core. The present study aimed to investigate whether a fully integrated OCT/NIRF imaging combined with a clinically available near-infrared fluorescence (NIRF) enhancing ICG can detect the inflamed, lipid-rich plaques in swine coronary atheromata whose phenotype is similar to human vulnerable fibroatheroma. Methods and Results: Accelerated atherosclerosis was made by coronary balloon denudation in alloxan induced diabetic minipigs. A rapid coronary imaging (20 mm/sec pullback speed) using a fully integrated OCT/NIRF catheter was safely performed 30 minutes after I.V. injection of ICG (2.0 mg/kg) just under contrast purge. OCT clearly identified the lipid-rich plaques with fibrous cap. Simultaneously acquired, distance-calibrated NIRF imaging detected lipid-laden macrophage signals in OCT-proven plaques (figure). The in vivo plaque target-to-background ratio (pTBR) was significantly higher in ICG-injected swine compared to non-diabetic swines or saline-injected controls (p<0.05), which was validated on ex vivo fluorescence reflectance imaging (FRI) (figure). The in vivo and ex vivo peak pTBRs correlated significantly (p<0.05). In vitro experiments, and histopathology including fluorescence microscopic imaging and immunostaining of the plaque sections corroborated the findings in vivo . Conlusions: An OCT/NIRF imaging with a clinical use of ICG accurately identified macrophage abundant, lipid-rich coronary plaques in diabetic atheromatous minipigs. This highly translatable dual-modal molecular-structural imaging could be relevant for clinical intracoronary detection of high-risk plaques.

Abstract 656: In Vivo Plaque Inflammation and Endothelial Permeability Independently Predict Atherosclerosis Progression: A Serial Multimodality Imaging Study

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Eric A Osborn ◽  
Giovanni J Ughi ◽  
Johan W Verjans ◽  
Edouard Gerbaud ◽  
Richard A Takx ◽  
...  
Keyword(s):  
Near Infrared ◽  
Ex Vivo ◽  
Multimodality Imaging ◽  
Endothelial Permeability ◽  
Imaging Study ◽  
Plaque Burden ◽  
Plaque Progression ◽  
Nirf Imaging ◽  
Imaging Results

Background: Atheroma inflammation impairs plaque stability and promotes plaque progression and complications. However, it is unknown how measures of plaque biology relate to changes in plaque burden, and whether plaque biology can independently predict plaque progression in coronary-sized arteries. This study evaluated the ability of intravascular near-infrared fluorescence (NIRF) biological imaging to inform experimental atheroma progression in vivo. Methods: Atherosclerosis was induced by balloon-injury in the aorta of 14 cholesterol-fed rabbits. Serial intravascular ultrasound (IVUS) and dual-modality intravascular NIRF - optical coherence tomography (OCT) imaging was performed following injection of a NIRF molecular imaging agent of plaque inflammatory protease activity (ProSense VM110; n=7), or impaired plaque endothelial permeability (indocyanine green (ICG); n=7). Plaque progression was further assessed by IVUS change in plaque burden. Regression analysis was used to evaluate the association of NIRF with plaque progression. In vivo imaging results were corroborated by ex vivo fluorescence reflectance imaging, fluorescence microscopy, and histopathology. Results: Quantitative analysis of 1,811 axial images spanning individual plaques, the change in NIRF plaque biological signals from 8 to 12 weeks strongly correlated with IVUS plaque burden from 8 to 12 weeks (ProSense VM110: r=0.774; ICG: r=0.572; p<0.0001). This finding remained significant on multivariate analysis adjusted for IVUS plaque burden, lumen area, and remodeling index (p<0.001). In additional multivariate analyses, the baseline NIRF signal at 8 weeks further predicted the magnitude of plaque progression even after adjustment for baseline plaque burden (p<0.001 for Prosense VM110; p=0.004 for ICG). Histology demonstrated NIRF agent uptake in inflamed, lipid-rich plaques. Conclusion: Plaque pathobiology and plaque burden progress in concert as assessed by translatable intravascular NIRF imaging technology. The baseline NIRF inflammation and impaired plaque permeability signals independently predict plaque progression. Integrated biological-microstructural imaging may enhance the ability to detect high-risk plaques at risk of progression.

scholarly journals Translation of c-Met Targeted Image-Guided Surgery Solutions in Oral Cavity Cancer—Initial Proof of Concept Data

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2674
Author(s):  
Tessa Buckle ◽  
Maarten van Alphen ◽  
Matthias N. van Oosterom ◽  
Florian van Beurden ◽  
Nina Heimburger ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Oral Cavity Cancer ◽  
Ex Vivo ◽  
Intermediate Step ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
Tumor Identification ◽  
Imaging Results ◽  
Pathological Evaluation ◽  
Fluorescence Camera

Intraoperative tumor identification (extension/margins/metastases) via receptor-specific targeting is one of the ultimate promises of fluorescence-guided surgery. The translation of fluorescent tracers that enable tumor visualization forms a critical component in the realization of this approach. Ex vivo assessment of surgical specimens after topical tracer application could help provide an intermediate step between preclinical evaluation and first-in-human trials. Here, the suitability of the c-Met receptor as a potential surgical target in oral cavity cancer was explored via topical ex vivo application of the fluorescent tracer EMI-137. Freshly excised tumor specimens obtained from ten patients with squamous cell carcinoma of the tongue were incubated with EMI-137 and imaged with a clinical-grade Cy5 prototype fluorescence camera. In-house developed image processing software allowed video-rate assessment of the tumor-to-background ratio (TBR). Fluorescence imaging results were related to standard pathological evaluation and c-MET immunohistochemistry. After incubation with EMI-137, 9/10 tumors were fluorescently illuminated. Immunohistochemistry revealed c-Met expression in all ten specimens. Non-visualization could be linked to a more deeply situated lesion. Tumor assessment was improved via video representation of the TBR (median TBR: 2.5 (range 1.8–3.1)). Ex vivo evaluation of tumor specimens suggests that c-Met is a possible candidate for fluorescence-guided surgery in oral cavity cancer.

scholarly journals Efficient Photoacoustic Imaging With Biomimetic Mesoporous Silica-Based Nanoparticles

2021 ◽  
Vol 9 ◽  
Author(s):  
Chuangjia Huang ◽  
Xiaoling Guan ◽  
Hui Lin ◽  
Lu Liang ◽  
Yingling Miao ◽  
...  
Keyword(s):  
Mesoporous Silica ◽  
Near Infrared ◽  
Ex Vivo ◽  
Photoacoustic Imaging ◽  
Mesoporous Silica Nanoparticles ◽  
Good Biocompatibility ◽  
Targeting Ability ◽  
Body Clearance

Indocyanine green (ICG), a near-infrared (NIR) fluorescent dye approved by the Food and Drug Administration (FDA), has been extensively used as a photoacoustic (PA) probe for PA imaging. However, its practical application is limited by poor photostability in water, rapid body clearance, and non-specificity. Herein, we fabricated a novel biomimetic nanoprobe by coating ICG-loaded mesoporous silica nanoparticles with the cancer cell membrane (namely, CMI) for PA imaging. This probe exhibited good dispersion, large loading efficiency, good biocompatibility, and homologous targeting ability to Hela cells in vitro. Furthermore, the in vivo and ex vivo PA imaging on Hela tumor-bearing nude mice demonstrated that CMI could accumulate in tumor tissue and display a superior PA imaging efficacy compared with free ICG. All these results demonstrated that CMI might be a promising contrast agent for PA imaging of cervical carcinoma.

scholarly journals NIRF-Molecular Imaging with Synovial Macrophages-Targeting Vsig4 Nanobody for Disease Monitoring in a Mouse Model of Arthritis

2019 ◽  
Vol 20 (13) ◽  
pp. 3347 ◽  
Author(s):  
Fang Zheng ◽  
Siyu Luo ◽  
Zhenlin Ouyang ◽  
Jinhong Zhou ◽  
Huanye Mo ◽  
...  
Keyword(s):  
Fluorescence Microscopy ◽  
Near Infrared ◽  
Single Photon ◽  
Ex Vivo ◽  
Photon Emission ◽  
Joint Inflammation ◽  
Experimental Arthritis ◽  
Emission Computed Tomography ◽  
Nirf Imaging

Nanobody against V-set and Ig domain-containing 4 (Vsig4) on tissue macrophages, such as synovial macrophages, could visualize joint inflammation in multiple experimental arthritis models via single-photon emission computed tomography imaging. Here, we further addressed the specificity and assessed the potential for arthritis monitoring using near-infrared fluorescence (NIRF) Cy7-labeled Vsig4 nanobody (Cy7-Nb119). In vivo NIRF-imaging of collagen-induced arthritis (CIA) was performed using Cy7-Nb119. Signals obtained with Cy7-Nb119 or isotope control Cy7-NbBCII10 were compared in joints of naive mice versus CIA mice. In addition, pathological microscopy and fluorescence microscopy were used to validate the arthritis development in CIA. Cy7-Nb119 accumulated in inflamed joints of CIA mice, but not the naive mice. Development of symptoms in CIA was reflected in increased joint accumulation of Cy7-Nb119, which correlated with the conventional measurements of disease. Vsig4 is co-expressed with F4/80, indicating targeting of the increasing number of synovial macrophages associated with the severity of inflammation by the Vsig4 nanobody. NIRF imaging with Cy7-Nb119 allows specific assessment of inflammation in experimental arthritis and provides complementary information to clinical scoring for quantitative, non-invasive and economical monitoring of the pathological process. Nanobody labelled with fluorescence can also be used for ex vivo validation experiments using flow cytometry and fluorescence microscopy.

scholarly journals ADAM22/LGI1 complex as a new actionable target for breast cancer brain metastasis

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Sara Charmsaz ◽  
Ben Doherty ◽  
Sinéad Cocchiglia ◽  
Damir Varešlija ◽  
Attilio Marino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
In Silico ◽  
Ex Vivo ◽  
Metastatic Breast ◽  
Peptide Mimetic ◽  
Breast Cancer Brain Metastasis

Abstract Background Metastatic breast cancer is a major cause of cancer-related deaths in woman. Brain metastasis is a common and devastating site of relapse for several breast cancer molecular subtypes, including oestrogen receptor-positive disease, with life expectancy of less than a year. While efforts have been devoted to developing therapeutics for extra-cranial metastasis, drug penetration of blood–brain barrier (BBB) remains a major clinical challenge. Defining molecular alterations in breast cancer brain metastasis enables the identification of novel actionable targets. Methods Global transcriptomic analysis of matched primary and metastatic patient tumours (n = 35 patients, 70 tumour samples) identified a putative new actionable target for advanced breast cancer which was further validated in vivo and in breast cancer patient tumour tissue (n = 843 patients). A peptide mimetic of the target’s natural ligand was designed in silico and its efficacy assessed in in vitro, ex vivo and in vivo models of breast cancer metastasis. Results Bioinformatic analysis of over-represented pathways in metastatic breast cancer identified ADAM22 as a top ranked member of the ECM-related druggable genome specific to brain metastases. ADAM22 was validated as an actionable target in in vitro, ex vivo and in patient tumour tissue (n = 843 patients). A peptide mimetic of the ADAM22 ligand LGI1, LGI1MIM, was designed in silico. The efficacy of LGI1MIM and its ability to penetrate the BBB were assessed in vitro, ex vivo and in brain metastasis BBB 3D biometric biohybrid models, respectively. Treatment with LGI1MIM in vivo inhibited disease progression, in particular the development of brain metastasis. Conclusion ADAM22 expression in advanced breast cancer supports development of breast cancer brain metastasis. Targeting ADAM22 with a peptide mimetic LGI1MIM represents a new therapeutic option to treat metastatic brain disease.

scholarly journals In Vivo Tracking of Murine Adipose Tissue-Derived Multipotent Adult Stem Cells and Ex Vivo Cross-Validation

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Chiara Garrovo ◽  
Natascha Bergamin ◽  
Dave Bates ◽  
Daniela Cesselli ◽  
Antonio Paolo Beltrami ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Optical Imaging ◽  
Adult Stem Cells ◽  
Near Infrared ◽  
Cross Validation ◽  
Ex Vivo ◽  
Imaging Data ◽  
Imaging Results

Stem cells are characterized by the ability to renew themselves and to differentiate into specialized cell types, while stem cell therapy is believed to treat a number of different human diseases through either cell regeneration or paracrine effects. Herein, an in vivo and ex vivo near infrared time domain (NIR TD) optical imaging study was undertaken to evaluate the migratory ability of murine adipose tissue-derived multipotent adult stem cells [mAT-MASC] after intramuscular injection in mice. In vivo NIR TD optical imaging data analysis showed a migration of DiD-labelled mAT-MASC in the leg opposite the injection site, which was confirmed by a fibered confocal microendoscopy system. Ex vivo NIR TD optical imaging results showed a systemic distribution of labelled cells. Considering a potential microenvironmental contamination, a cross-validation study by multimodality approaches was followed: mAT-MASC were isolated from male mice expressing constitutively eGFP, which was detectable using techniques of immunofluorescence and qPCR. Y-chromosome positive cells, injected into wild-type female recipients, were detected by FISH. Cross-validation confirmed the data obtained by in vivo/ex vivo TD optical imaging analysis. In summary, our data demonstrates the usefulness of NIR TD optical imaging in tracking delivered cells, giving insights into the migratory properties of the injected cells.

IN VIVO NEAR-INFRARED FLUORESCENCE IMAGING OF HUMAN COLON ADENOCARCINOMA BY SPECIFIC IMMUNOTARGETING OF A TUMOR-ASSOCIATED MUCIN

2009 ◽  
Vol 02 (04) ◽  
pp. 407-422 ◽  
Author(s):  
RALPH S. DACOSTA ◽  
YING TANG ◽  
TUULA KALLIOMAKI ◽  
RAYMOND M. REILLY ◽  
ROBERT WEERSINK ◽  
...  
Keyword(s):  
Fluorescence Microscopy ◽  
Fluorescence Imaging ◽  
Normal Tissue ◽  
Near Infrared ◽  
Ex Vivo ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Human Colon Adenocarcinoma

Background and Aims: Accurate endoscopic detection of premalignant lesions and early cancers in the colon is essential for cure, since prognosis is closely related to lesion size and stage. Although it has great clinical potential, autofluorescence endoscopy has limited tumor-to-normal tissue image contrast for detecting small preneoplastic lesions. We have developed a molecularly specific, near-infrared fluorescent monoclonal antibody (CC49) bioconjugate which targets tumor-associated glycoprotein 72 (TAG72), as a contrast agent to improve fluorescence-based endoscopy of colon cancer. Methods: The fluorescent anti-TAG72 conjugate was evaluated in vitro and in vivo in athymic nude mice bearing human colon adenocarcinoma (LS174T) subcutaneous tumors. Autofluorescence, a fluorescent but irrelevant antibody and the free fluorescent dye served as controls. Fluorescent agents were injected intravenously, and in vivo whole body fluorescence imaging was performed at various time points to determine pharmacokinetics, followed by ex vivo tissue analysis by confocal fluorescence microscopy and histology. Results: Fluorescence microscopy and histology confirmed specific LS174T cell membrane targeting of labeled CC49 in vitro and ex vivo. In vivo fluorescence imaging demonstrated significant tumor-to-normal tissue contrast enhancement with labeled-CC49 at three hours post injection, with maximum contrast after 48 h. Accumulation of tumor fluorescence demonstrated that modification of CC49 antibodies did not alter their specific tumor-localizing properties, and was antibody-dependent since controls did not produce detectable tumor fluorescence. Conclusions: These results show proof-of-principle that our near-infrared fluorescent-antibody probe targeting a tumor-associated mucin detects colonic tumors at the molecular level in real time, and offer a basis for future improvement of image contrast during clinical fluorescence endoscopy.

scholarly journals Nanocurcumin-Loaded UCNPs for Cancer Theranostics: Physicochemical Properties, In Vitro Toxicity, and In Vivo Imaging Studies

Nanomaterials ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2234
Author(s):  
Anbharasi Lakshmanan ◽  
Roman A. Akasov ◽  
Natalya V. Sholina ◽  
Polina A. Demina ◽  
Alla N. Generalova ◽  
...  
Keyword(s):  
Near Infrared ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Laboratory Animals ◽  
In Vitro Toxicity ◽  
Upconversion Nanoparticles ◽  
Lewis Lung Cancer ◽  
Spectral Bands

Formulation of promising anticancer herbal drug curcumin as a nanoscale-sized curcumin (nanocurcumin) improved its delivery to cells and organisms both in vitro and in vivo. We report on coupling nanocurcumin with upconversion nanoparticles (UCNPs) using Poly (lactic-co-glycolic Acid) (PLGA) to endow visualisation in the near-infrared transparency window. Nanocurcumin was prepared by solvent-antisolvent method. NaYF4:Yb,Er (UCNP1) and NaYF4:Yb,Tm (UCNP2) nanoparticles were synthesised by reverse microemulsion method and then functionalized it with PLGA to form UCNP-PLGA nanocarrier followed up by loading with the solvent-antisolvent process synthesized herbal nanocurcumin. The UCNP samples were extensively characterised with XRD, Raman, FTIR, DSC, TGA, UV-VIS-NIR spectrophotometer, Upconversion spectrofluorometer, HRSEM, EDAX and Zeta Potential analyses. UCNP1-PLGA-nanocurcumin exhibited emission at 520, 540, 660 nm and UCNP2-PLGA-nanocurmin showed emission at 480 and 800 nm spectral bands. UCNP-PLGA-nanocurcumin incubated with rat glioblastoma cells demonstrated moderate cytotoxicity, 60–80% cell viability at 0.12–0.02 mg/mL marginally suitable for therapeutic applications. The cytotoxicity of UCNPs evaluated in tumour spheroids models confirmed UCNP-PLGA-nanocurcumin therapeutic potential. As-synthesised curcumin-loaded nanocomplexes were administered in tumour-bearing laboratory animals (Lewis lung cancer model) and showed adequate contrast to enable in vivo and ex vivo study of UCNP-PLGA-nanocurcumin bio distribution in organs, with dominant distribution in the liver and lungs. Our studies demonstrate promise of nanocurcumin-loaded upconversion nanoparticles for theranostics applications.

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