Everolimus-eluting stents stabilize plaque inflammation in vivo: assessment by intravascular fluorescence molecular imaging

The ability to visualize molecular processes and cellular regulators of complex pulmonary diseases such as asthma, chronic obstructive pulmonary disease (COPD), or adult respiratory distress syndrome (ARDS), would aid in the diagnosis, differentiation, therapy assessment and in small animal-based drug-discovery processes. Herein we report the application of normalized transillumination and fluorescence molecular tomography (FMT) for the noninvasive quantitative imaging of the mouse lung in vivo. We demonstrate the ability to visualize and quantitate pulmonary response in a murine model of LPS-induced airway inflammation. Twenty-four hours prior to imaging, BALB/c female mice were injected via tail vein with 2 nmol of a cathepsin-sensitive activatable fluorescent probe (excitation: 750 nm; emission: 780 nm) and 2 nmol of accompanying intravascular agent (excitation: 674 nm; emission: 694 nm). Six hours later, the mice were anesthetized with isoflurane and administered intranasal LPS in sterile 0.9% saline in 25 μl aliquots (one per nostril). Fluorescence molecular imaging revealed the in vivo profile of cysteine protease activation and vascular distribution within the lung typifying the inflammatory response to LPS insult. Results were correlated with standard in vitro laboratory tests (Western blot, bronchoalveolar lavage or BAL analysis, immunohistochemistry) and revealed good correlation with the underlying activity. We demonstrated the capacity of fluorescence tomography to noninvasively and longitudinally characterize physiological, cellular, and subcellular processes associated with inflammatory disease burden in the lung. The data presented herein serve to further evince fluorescence molecular imaging as a technology highly appropriate for the biomedical laboratory.

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Enhancing in vivo renal ischemia assessment by high-dynamic-range fluorescence molecular imaging

Journal of Biomedical Optics ◽

10.1117/1.jbo.23.7.076009 ◽

2018 ◽

Vol 23 (07) ◽

pp. 1

Author(s):

Yang Gao ◽

Yuan Zhou ◽

Fei Liu ◽

Jianwen Luo

Keyword(s):

Molecular Imaging ◽

Dynamic Range ◽

High Dynamic Range ◽

Renal Ischemia ◽

High Dynamic ◽

Fluorescence Molecular Imaging

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VEGF-targeted multispectral optoacoustic tomography and fluorescence molecular imaging in human carotid atherosclerotic plaques

10.21203/rs.3.rs-428529/v1 ◽

2021 ◽

Author(s):

Pieter J. Steinkamp ◽

Jasper Vonk ◽

Lydian A. Huisman ◽

Gert-Jan Meersma ◽

Gilles F.H. Diercks ◽

...

Keyword(s):

Molecular Imaging ◽

Carotid Artery ◽

Ex Vivo ◽

Carotid Plaques ◽

Symptomatic Carotid ◽

Optoacoustic Tomography ◽

Imaging Results ◽

Human Carotid ◽

Fluorescence Molecular Imaging

Abstract Background: Vulnerable atherosclerotic carotid plaques are prone to rupture resulting in ischemic strokes. Molecular imaging techniques have the potential to assess plaque vulnerability by visualizing molecular markers. Bevacizumab-800CW is a near-infrared fluorescent contrast agent antibody targeting vascular endothelial growth factor-A (VEGF-A). Here, we study if administration of bevacizumab-800CW is safe and can be visualized using multispectral optoacoustic tomography (MSOT) to evaluate atherosclerotic carotid plaques in vivo by visualizing intra-plaque neovascularization.Methods: Healthy volunteers were imaged with MSOT to determine the technical feasibility of human carotid imaging with MSOT. Patients with symptomatic carotid artery stenosis scheduled for carotid artery endarterectomy were intravenously administered with a bolus injection of 4.5 mg bevacizumab-800CW. Before and two days after tracer administration, in vivo non-invasive MSOT was performed. For validation, ex vivo fluorescence molecular imaging of the surgically removed plaque specimen was performed and correlated with histopathology.Results: Administration of 4.5 mg bevacizumab-800CW was safe in five patients. MSOT achieved accurate visualization of the carotid bifurcation area and assessment of the plaque in all five patients. Bevacizumab-800CW-resolved signal could not be detected with MSOT prior to surgery. However, ex vivo analysis of the carotid plaque showed accumulation of bevacizumab-800CW.Conclusions: These first-in-human MSOT and fluorescence molecular imaging results in carotid artery plaques suggest that bevacizumab is a potential tracer for imaging of vulnerable plaques. However, the microdose used here cannot be detected with MSOT. A subsequent phase I dose-finding study is needed to evaluate bevacizumab-800CW in higher doses as a useful optoacoustic imaging agent. Moreover, the development of dedicated optoacoustic contrast agents for signal attenuation of the targeting moiety is advisable for carotid atherosclerotic plaque assessment using MSOT.

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DEVELOPMENT OF NEEDLE-BASED MICROENDOSCOPY FOR FLUORESCENCE MOLECULAR IMAGING OF BREAST TUMOR MODELS

Journal of Innovative Optical Health Sciences ◽

10.1142/s1793545809000747 ◽

2009 ◽

Vol 02 (04) ◽

pp. 343-352

Author(s):

CHAO-WEI CHEN ◽

TIFFANY R. BLACKWELL ◽

RENEE NAPHAS ◽

PAUL T. WINNARD ◽

VENU RAMAN ◽

...

Keyword(s):

Breast Cancer ◽

Molecular Imaging ◽

Contrast Agents ◽

Breast Biopsy ◽

Fluorescent Imaging ◽

Model Systems ◽

Breast Cancers ◽

Imaging Device ◽

Fluorescence Molecular Imaging

Fluorescence molecular imaging enables the visualization of basic molecular processes such as gene expression, enzyme activity, and disease-specific molecular interactions in vivo using targeted contrast agents, and therefore, is being developed for early detection and in situ characterization of breast cancers. Recent advances in developing near-infrared fluorescent imaging contrast agents have enabled the specific labeling of human breast cancer cells in mouse model systems. In synergy with contrast agent development, this paper describes a needle-based fluorescence molecular imaging device that has the strong potential to be translated into clinical breast biopsy procedures. This microendoscopy probe is based on a gradient-index (GRIN) lens interfaced with a laser scanning microscope. Specifications of the imaging performance, including the field-of-view, transverse resolution, and focus tracking characteristics were calibrated. Orthotopic MDA-MB-231 breast cancer xenografts stably expressing the tdTomato red fluorescent protein (RFP) were used to detect the tumor cells in this tumor model as a proof of principle study. With further development, this technology, in conjunction with the development of clinically applicable, injectable fluorescent molecular imaging agents, promises to perform fluorescence molecular imaging of breast cancers in vivo for breast biopsy guidance.

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