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

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.

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

Molecular Imaging ◽

10.1155/2021/5540569 ◽

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.

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Efficient Photoacoustic Imaging With Biomimetic Mesoporous Silica-Based Nanoparticles

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.762956 ◽

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.

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

International Journal of Molecular Sciences ◽

10.3390/ijms20133347 ◽

2019 ◽

Vol 20 (13) ◽

pp. 3347 ◽

Cited By ~ 2

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.

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

Journal of Innovative Optical Health Sciences ◽

10.1142/s1793545809000759 ◽

2009 ◽

Vol 02 (04) ◽

pp. 407-422 ◽

Cited By ~ 3

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.

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

Nanomaterials ◽

10.3390/nano11092234 ◽

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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Microscale optoelectronic infrared-to-visible upconversion devices and their use as injectable light sources

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1802064115 ◽

2018 ◽

Vol 115 (26) ◽

pp. 6632-6637 ◽

Cited By ~ 31

Author(s):

He Ding ◽

Lihui Lu ◽

Zhao Shi ◽

Dan Wang ◽

Lizhu Li ◽

...

Keyword(s):

Near Infrared ◽

Biological Fluids ◽

Visible Spectral Range ◽

Infrared Light ◽

Light Sources ◽

Fully Integrated ◽

Broadband Absorption ◽

In Vivo Experiments

Optical upconversion that converts infrared light into visible light is of significant interest for broad applications in biomedicine, imaging, and displays. Conventional upconversion materials rely on nonlinear light-matter interactions, exhibit incidence-dependent efficiencies, and require high-power excitation. We report an infrared-to-visible upconversion strategy based on fully integrated microscale optoelectronic devices. These thin-film, ultraminiaturized devices realize near-infrared (∼810 nm) to visible [630 nm (red) or 590 nm (yellow)] upconversion that is linearly dependent on incoherent, low-power excitation, with a quantum yield of ∼1.5%. Additional features of this upconversion design include broadband absorption, wide-emission spectral tunability, and fast dynamics. Encapsulated, freestanding devices are transferred onto heterogeneous substrates and show desirable biocompatibilities within biological fluids and tissues. These microscale devices are implanted in behaving animals, with in vitro and in vivo experiments demonstrating their utility for optogenetic neuromodulation. This approach provides a versatile route to achieve upconversion throughout the entire visible spectral range at lower power and higher efficiency than has previously been possible.

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Feasibility of ex vivo fluorescence imaging of angiogenesis in (non-) culprit human carotid atherosclerotic plaques using bevacizumab-800CW

Scientific Reports ◽

10.1038/s41598-021-82568-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lydian A. Huisman ◽

Pieter J. Steinkamp ◽

Jan-Luuk Hillebrands ◽

Clark J. Zeebregts ◽

Matthijs D. Linssen ◽

...

Keyword(s):

Near Infrared ◽

Ex Vivo ◽

Fluorescent Antibody ◽

Atherosclerotic Plaques ◽

Over Expression ◽

Nirf Imaging ◽

Pathologic Features ◽

Atherosclerotic Process ◽

Endothelial Growth Factor

AbstractVascular endothelial growth factor-A (VEGF-A) is assumed to play a crucial role in the development and rupture of vulnerable plaques in the atherosclerotic process. We used a VEGF-A targeted fluorescent antibody (bevacizumab-IRDye800CW [bevacizumab-800CW]) to image and visualize the distribution of VEGF-A in (non-)culprit carotid plaques ex vivo. Freshly endarterectomized human plaques (n = 15) were incubated in bevacizumab-800CW ex vivo. Subsequent NIRF imaging showed a more intense fluorescent signal in the culprit plaques (n = 11) than in the non-culprit plaques (n = 3). A plaque received from an asymptomatic patient showed pathologic features similar to the culprit plaques. Cross-correlation with VEGF-A immunohistochemistry showed co-localization of VEGF-A over-expression in 91% of the fluorescent culprit plaques, while no VEGF-A expression was found in the non-culprit plaques (p < 0.0001). VEGF-A expression was co-localized with CD34, a marker for angiogenesis (p < 0.001). Ex vivo near-infrared fluorescence (NIRF) imaging by incubation with bevacizumab-800CW shows promise for visualizing VEGF-A overexpression in culprit atherosclerotic plaques in vivo.

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Fluorescence-guided surgery using indocyanine green in dogs with superficial solid tumours

Veterinary Record ◽

10.1136/vr.105554 ◽

2020 ◽

Vol 187 (7) ◽

pp. 273-273

Author(s):

Sophie Favril ◽

Eline Abma ◽

Emmelie Stock ◽

Nausikaa Devriendt ◽

Bart Van Goethem ◽

...

Keyword(s):

Indocyanine Green ◽

Near Infrared ◽

Ex Vivo ◽

False Positive Rate ◽

Tumour Tissue ◽

Surrounding Tissue ◽

Tumour Resection ◽

Nirf Imaging ◽

Tumour Delineation

BackgroundNear-infrared fluorescence (NIRF) imaging is a relatively novel technique that can aid surgeons during intraoperative tumour identification.MethodsNine canine oncology patients (five mammary gland tumours, three mast cell tumours and one melanoma) received intravenous indocyanine green (ICG). After 24 hours, tumours were resected and fluorescence intensities of tumours and surroundings were evaluated. Additional wound bed tissue was resected if residual fluorescence was present after tumour resection. Ex vivo, fluorescence-guided dissection was performed to separate tumour from surrounding tissue.ResultsIntraoperative NIRF-guided tumour delineation was feasible in four out of nine dogs. Wound bed imaging after tumour removal identified nine additional fluorescent lesions, of which four contained tumour tissue. One of these four true positive in vivo lesions was missed by standard-of-care inspection. Ex vivo fluorescence-guided tumour dissection showed a sensitivity of 72 per cent and a specificity of 80 per cent in discriminating between tumour and surrounding tissue.ConclusionThe value of ICG for intraoperative tumour delineation seems more limited than originally thought. Although NIRF imaging using ICG did identify remaining tumour tissue in the wound bed, a high false positive rate was also observed.

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Liposomal Chitosan-N-Acetyl Cysteine Nanoparticle for In-Vitro/In-Vivo Near Infrared Fluorescent (NIR) Imaging

10.26434/chemrxiv.9976145.v1 ◽

2019 ◽

Author(s):

Piyush Kumar ◽

Timothy Van Treuren ◽

Amalendu Ranjan ◽

Jamboor K Vishwanatha

Keyword(s):

Near Infrared ◽

Infrared Imaging ◽

Tumor Imaging ◽

Ex Vivo ◽

Breast Cancer Cell Lines ◽

Nir Imaging ◽

Negative Surface ◽

Acetyl Cysteine

<p>In this work, we studied the effect of chitosan conjugated N-acetyl cysteine (CHT-NAC) coating on liposomal (DMPC:14 lysoPG: DSPE-2000-NH2) nanoparticles as a vehicle to cross the blood-brain barrier. The size of lipo-NP and Lipo-CHT-NAC NP were sub 50 nm with negative surface charge consistent with its use in an intravenous application. In vitro near infrared (NIR) imaging showed good cellular uptake in two triple-negative breast cancer cell lines (MDA-MB-231 and brain metastatic MDA-MB-831). Live (4-120 h) and ex-vivo near-infrared imaging at 24 h in nude mice showed the extended circulation of CHT-NAC Lipo-NP. These results demonstrated that Lipo-CHT-NAC NP could be used for metastatic brain tumor imaging.</p>

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