In vivo long-term investigation of tumor bearing mKate2 by an in-house fluorescence molecular imaging system

Abstract Background Transpathology highlights the interpretation of the underlying physiology behind molecular imaging. However, it remains challenging due to the discrepancies between in vivo and in vitro measurements and difficulties of precise co-registration between trans-scaled images. This study aims to develop a multimodal intravital molecular imaging (MIMI) system as a tool for in vivo tumour transpathology investigation. Methods The proposed MIMI system integrates high-resolution positron imaging, magnetic resonance imaging (MRI) and microscopic imaging on a dorsal skin window chamber on an athymic nude rat. The window chamber frame was designed to be compatible with multimodal imaging and its fiducial markers were customized for precise physical alignment among modalities. The co-registration accuracy was evaluated based on phantoms with thin catheters. For proof of concept, tumour models of the human colorectal adenocarcinoma cell line HT-29 were imaged. The tissue within the window chamber was sectioned, fixed and haematoxylin–eosin (HE) stained for comparison with multimodal in vivo imaging. Results The final MIMI system had a maximum field of view (FOV) of 18 mm × 18 mm. Using the fiducial markers and the tubing phantom, the co-registration errors are 0.18 ± 0.27 mm between MRI and positron imaging, 0.19 ± 0.22 mm between positron imaging and microscopic imaging and 0.15 ± 0.27 mm between MRI and microscopic imaging. A pilot test demonstrated that the MIMI system provides an integrative visualization of the tumour anatomy, vasculatures and metabolism of the in vivo tumour microenvironment, which was consistent with ex vivo pathology. Conclusions The established multimodal intravital imaging system provided a co-registered in vivo platform for trans-scale and transparent investigation of the underlying pathology behind imaging, which has the potential to enhance the translation of molecular imaging.

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A Molecular Imaging System Based on Both Transcriptional and Genomic Amplification to Detect Prostate Cancer Cells In Vivo

Molecular Therapy ◽

10.1038/mt.2012.259 ◽

2013 ◽

Vol 21 (3) ◽

pp. 554-560 ◽

Cited By ~ 5

Author(s):

Frédéric Pouliot ◽

Makoto Sato ◽

Ziyue Karen Jiang ◽

Steve Huyn ◽

Breanne DW Karanikolas ◽

...

Keyword(s):

Prostate Cancer ◽

Molecular Imaging ◽

Cancer Cells ◽

Imaging System ◽

Prostate Cancer Cells ◽

Genomic Amplification ◽

Detect Prostate Cancer

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Visualization of pulmonary inflammation using noninvasive fluorescence molecular imaging

Journal of Applied Physiology ◽

10.1152/japplphysiol.00959.2007 ◽

2008 ◽

Vol 104 (3) ◽

pp. 795-802 ◽

Cited By ~ 72

Author(s):

Jodi Haller ◽

Damon Hyde ◽

Nikolaos Deliolanis ◽

Ruben de Kleine ◽

Mark Niedre ◽

...

Keyword(s):

Molecular Imaging ◽

Quantitative Imaging ◽

Pulmonary Inflammation ◽

Small Animal ◽

Mouse Lung ◽

Chronic Obstructive ◽

Therapy Assessment ◽

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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Fluorescence molecular imaging system with a novel mouse surface extraction method and a rotary scanning scheme

10.1117/12.2076476 ◽

2015 ◽

Cited By ~ 1

Author(s):

Yue Zhao ◽

Dianwen Zhu ◽

Reheman Baikejiang ◽

Changqing Li

Keyword(s):

Molecular Imaging ◽

Extraction Method ◽

Imaging System ◽

Surface Extraction ◽

Scanning Scheme ◽

Fluorescence Molecular Imaging

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Long-Term Prophylaxis and Pharmacokinetic Evaluation of Intramuscular Nano- and Microparticle Decoquinate in Mice Infected with P. berghei Sporozoites

Malaria Research and Treatment ◽

10.1155/2017/7508291 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Qigui Li ◽

Lisa Xie ◽

Diana Caridha ◽

Qiang Zeng ◽

Jing Zhang ◽

...

Keyword(s):

Drug Exposure ◽

Imaging System ◽

Pharmacokinetic Studies ◽

Efficacy Evaluation ◽

Liver Stage ◽

Intramuscular Dose ◽

In Vivo Imaging System ◽

Nanoparticle Formulation

Decoquinate nanoparticle and microparticle suspended in an oily vehicle to retard drug release are evaluated for long-term malaria prophylaxis. Pharmacokinetic studies in normal animals and antimalarial efficacy in liver stage malaria mice were conducted at various single intramuscular-decoquinate doses for 2, 4, 6, or 8 weeks prior to infection with P. berghei sporozoites. The liver stage efficacy evaluation was monitored by using an in vivo imaging system. Full causal prophylaxis was shown in mice with a single intramuscular dose at 120 mg/kg of nanoparticle decoquinate (0.43 μm) for 2-3 weeks and with microparticle decoquinate (8.31 μm) injected 8 weeks earlier than inoculation. The time above MIC of 1,375 hr observed with the microparticle formulation provided a 2.2-fold longer drug exposure than with the nanoparticle formulation (624 hr). The prophylactic effect of the microparticle formulation observed in mice was shown to be 3-4 times longer than the nanoparticle decoquinate formulation.

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

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jew228 ◽

2016 ◽

Vol 18 (5) ◽

pp. 510-518 ◽

Cited By ~ 10

Author(s):

Marcella A. Calfon Press ◽

Georgios Mallas ◽

Amir Rosenthal ◽

Tetsuya Hara ◽

Adam Mauskapf ◽

...

Keyword(s):

Molecular Imaging ◽

Plaque Inflammation ◽

In Vivo Assessment ◽

Fluorescence Molecular Imaging

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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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Abstract 14935: Targeted Optical Molecular Imaging of Atheroma Calcification Using Novel Aldendronate-based Probe

Circulation ◽

10.1161/circ.142.suppl_3.14935 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Dong Oh Kang ◽

Yong Geun Lim ◽

Joon Woo Song ◽

Ye Hee Park ◽

Hyun Jung Kim ◽

...

Keyword(s):

Molecular Imaging ◽

High Resolution ◽

Murine Model ◽

Calcium Binding ◽

Laser Scanning ◽

Near Infrared ◽

Imaging System ◽

Whole Body ◽

Imaging Results

Background/Objectives: Vascular spotty calcification is an actively regulated biological process resulting in plaque vulnerability. We investigated the feasibility of a novel alendronate-based near-infrared fluorescence (NIRF)-emitting probe to specifically target atherosclerotic calcification in a murine model in vivo using our customized high-resolution multichannel intravital molecular imaging system (IVFM). Methods/Results: We have fabricated a calcium-binding NIRF probe by chemically coupling alendronate, a specific targeting ligand, and NIRF-emitting Cy5.5 to the ends of azide-PEG-NHS ester (Al-Cy5.5). Prepared Al-Cy5.5 has high affinity for calcium phosphate-containing bone minerals. In vitro, Al-Cy5.5 specifically binds to RANKL-induced osteogenic-macrophages as compared to macrophages (p<0.01). On whole body fluorescence imaging to assess time-dependent excretion, NIRF signals remained visible up to 48 hrs. Then, in mice with calcified plaque induced by a combination diet of high-cholesterol and warfarin, Al-Cy5.5 (2.5 mg/kg) was intravenously injected. 48 hrs after administration, murine calcified atheroma was assessed using a customized high-resolution multichannel IVFM, which demonstrated highly enhanced NIRF signals in vivo in the calcified areas of murine carotid plaques (p<0.01, Figure). Ex vivo laser scanning fluorescence microscopic and immune-histological findings from the corresponding sister sections well corroborated the in vivo imaging results, which demonstrated the co-localization of NIRF signals with plaque calcifications (von-Kossa stain). Conclusions: Our novel calcification targeted probe, Al-Cy5.5, was able to selectively target atheroma calcification in vivo in a murine model as assessed by optical IVFM. This novel targetable strategy is expected to provide a promising theranostic basis for calcified high-risk plaques by integration with multimodal customized catheter imaging system.

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