scholarly journals A rapid dynamic in vivo near-infrared fluorescence imaging assay to track lung vascular permeability after acute radiation injury

2021 ◽  
Author(s):  
Jaidip Manikrao Jagtap ◽  
Said H. Audi ◽  
Mir Hadi Razeghi-Kondelaji ◽  
Brian L Fish ◽  
Christopher P Hansen ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Fluorescence Imaging ◽  
Near Infrared ◽  
Radiation Injury ◽  
Ex Vivo ◽  
Nir Fluorescence ◽  
Permeability Surface ◽  
Area Product ◽  
Lung Vascular Permeability

Purpose: Develop an in vivo near-infrared (NIR) fluorescence imaging assay to quantify sequential changes in lung vascular permeability-surface area product (PS) in rodents. Methods: Dynamic NIR imaging methods for determining lung vascular permeability-surface area product were developed and tested on non-irradiated and 13 Gy irradiated rats with/without treatment with lisinopril. A physiologically-based pharmacokinetic (PBPK) model of Indocyanine Green (ICG) pulmonary disposition was applied to in vivo imaging data and PS was estimated. In vivo results were validated by five accepted assays: ex vivo perfused lung imaging, endothelial filtration coefficient (Kf) measurement, pulmonary vascular resistance measurement, Evan's blue dye uptake and histopathology. Results: PBPK modeled lung PS increased from 2.60±0.40 [CL: 2.42-2.78] mL/min in the non-irradiated group to 6.94±8.25 [CL: 3.56-10.31] mL/min in 13 Gy group after 42 days. Lisinopril treatment lowered PS in the 13Gy group to 4.76±6.17 [CL: 2.12-7.40] mL/min. A higher 5X change in PS was observed in rats exhibiting severe radiation injury. Ex vivo Kf (mL/min/cm H2O/g dry lung weight), a measure of pulmonary vascular permeability, showed similar trends in lungs of irradiated rats (0.164±0.081 [CL: 0.11-0.22]) compared to non-irradiated controls (0.022±0.003 [CL: 0.019-0.025]), with reduction to 0.070±0.035 [CL: 0.045-0.096] for irradiated rats treated with lisinopril. Similar trends were observed for ex vivo pulmonary vascular resistance, Evan's blue uptake, and histopathology. Conclusion: Our results suggest that dynamic in vivo NIR fluorescence imaging can replace current terminal assays. In vivo imaging accurately tracks changes in PS and lung interstitial transport in response to radiation injury.

scholarly journals Retro-enantio isomer of angiopep-2 assists nanoprobes across the blood-brain barrier for targeted magnetic resonance/fluorescence imaging of glioblastoma

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Ruoxi Xie ◽  
Zijun Wu ◽  
Fanxin Zeng ◽  
Huawei Cai ◽  
Dan Wang ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Fluorescence Imaging ◽  
Near Infrared ◽  
Ex Vivo ◽  
Malignant Gliomas ◽  
Resonance Fluorescence ◽  
Malignant Tumours ◽  
Nir Fluorescence

AbstractGlioblastoma (GBM), one of the most common primary intracranial malignant tumours, is very difficult to be completely excised by surgery due to its irregular shape. Here, we use an MRI/NIR fluorescence dual-modal imaging nanoprobe that includes superparamagnetic iron oxide nanoparticles (SPIONs) modified with indocyanine (Cy7) molecules and peptides (ANG or DANG) to locate malignant gliomas and guide accurate excision. Both peptides/Cy7-SPIONs probes displayed excellent tumour-homing properties and barrier penetrating abilities in vitro, and both could mediate precise aggregation of the nanoprobes at gliomas sites in in vivo magnetic resonance imaging (MRI) and ex vivo near-infrared (NIR) fluorescence imaging. However, compared with ANG/Cy7-SPIONs probes, DANG/Cy7-SPIONs probes exhibited better enhanced MR imaging effects. Combining all these features together, this MRI/NIR fluorescence imaging dual-modal nanoprobes modified with retro-enantio isomers of the peptide have the potential to accurately display GBMs preoperatively for precise imaging and intraoperatively for real-time imaging.

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 Rational design of a NIR-II fluorescent nano-system with maximized fluorescence performance and applications

2021 ◽  
Author(s):  
Haoli Yu ◽  
Yuesong Wang ◽  
Yan Chen ◽  
Min Ji
Keyword(s):  
Fluorescence Imaging ◽  
In Vivo Imaging ◽  
Rational Design ◽  
Near Infrared ◽  
Nir Fluorescence

Purpose: Near-infrared (NIR) fluorescence imaging (FI) become a research hotspot in the field of in vivo imaging. Here, we intend to synthesize a NIR-II fluorescence nano-system with an excellent fluorescence...

scholarly journals Multimodal Mn-doped I–III–VI quantum dots for near infrared fluorescence and magnetic resonance imaging: from synthesis to in vivo application

Nanoscale ◽  
2014 ◽  
Vol 6 (15) ◽  
pp. 9264-9272 ◽  
Author(s):  
Gary Sitbon ◽  
Sophie Bouccara ◽  
Mariana Tasso ◽  
Aurélie Francois ◽  
Lina Bezdetnaya ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Quantum Dots ◽  
Magnetic Resonance ◽  
Fluorescence Imaging ◽  
Near Infrared ◽  
Resonance Imaging ◽  
Near Infrared Fluorescence ◽  
Nir Fluorescence ◽  
Mn Doped

Cadmium-free quantum dots doped with Mn2+ions show promising results forin vivobimodal MRI and NIR fluorescence imaging.

scholarly journals Intraoperative Near-infrared Fluorescence Imaging with Novel Indocyanine Green-Loaded Nanocarrier for Spinal Metastasis: A Preliminary Animal Study

2012 ◽  
Vol 6 (1) ◽  
pp. 80-84 ◽  
Author(s):  
Toru Funayama ◽  
Masataka Sakane ◽  
Tetsuya Abe ◽  
Isao Hara ◽  
Eiichi Ozeki ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Fluorescence Imaging ◽  
Rat Model ◽  
Near Infrared ◽  
Imaging Modality ◽  
Intraoperative Imaging ◽  
Spinal Metastasis ◽  
Vena Cava ◽  
Nir Fluorescence

Marginal resection during resection of a spinal metastasis is frequently difficult because of the presence of important tissues such as the aorta, vena cava, and dura mater, including the spinal cord adjacent to the vertebral body. Thus, there is an urgent need for novel intraoperative imaging modalities with the ability to clearly identify bone metastasis. We have proposed a novel nanocarrier loaded with indocyanine green (ICG) (ICG-lactosome) with tumor selectivity attributable to its enhanced permeation and retention (EPR) effect. We studied its feasibility in intraoperative near-infrared (NIR) fluorescence diagnosis with ICG-lactosome for imaging spinal metastasis. A rat model of subcutaneous mammary tumor and a rat model of spinal metastasis of breast cancer were used. Fluorescence emitted by the subcutaneous tumors and the spinal metastasis were clearly detected for at least 24 h. Moreover, imaging of the dissected spine revealed clear fluorescence emitted by the metastatic lesion in the L6 vertebra while the normal bone lacked fluorescence. This study was the first report on NIR fluorescence imaging of spinal metastasis in vivo. NIR fluorescence imaging with ICG-lactosome could be an effective intraoperative imaging modality for detecting spinal metastasis.

scholarly journals Shortwave infrared fluorescence imaging with the clinically approved near-infrared dye indocyanine green

2018 ◽  
Vol 115 (17) ◽  
pp. 4465-4470 ◽  
Author(s):  
Jessica A. Carr ◽  
Daniel Franke ◽  
Justin R. Caram ◽  
Collin F. Perkinson ◽  
Mari Saif ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Real Time ◽  
Fluorescence Imaging ◽  
Near Infrared ◽  
Emission Spectra ◽  
Nir Fluorescence ◽  
Near Infrared Dye ◽  
Silicon Based ◽  
Shortwave Infrared

Fluorescence imaging is a method of real-time molecular tracking in vivo that has enabled many clinical technologies. Imaging in the shortwave IR (SWIR; 1,000–2,000 nm) promises higher contrast, sensitivity, and penetration depths compared with conventional visible and near-IR (NIR) fluorescence imaging. However, adoption of SWIR imaging in clinical settings has been limited, partially due to the absence of US Food and Drug Administration (FDA)-approved fluorophores with peak emission in the SWIR. Here, we show that commercially available NIR dyes, including the FDA-approved contrast agent indocyanine green (ICG), exhibit optical properties suitable for in vivo SWIR fluorescence imaging. Even though their emission spectra peak in the NIR, these dyes outperform commercial SWIR fluorophores and can be imaged in the SWIR, even beyond 1,500 nm. We show real-time fluorescence imaging using ICG at clinically relevant doses, including intravital microscopy, noninvasive imaging in blood and lymph vessels, and imaging of hepatobiliary clearance, and show increased contrast compared with NIR fluorescence imaging. Furthermore, we show tumor-targeted SWIR imaging with IRDye 800CW-labeled trastuzumab, an NIR dye being tested in multiple clinical trials. Our findings suggest that high-contrast SWIR fluorescence imaging can be implemented alongside existing imaging modalities by switching the detection of conventional NIR fluorescence systems from silicon-based NIR cameras to emerging indium gallium arsenide-based SWIR cameras. Using ICG in particular opens the possibility of translating SWIR fluorescence imaging to human clinical applications. Indeed, our findings suggest that emerging SWIR-fluorescent in vivo contrast agents should be benchmarked against the SWIR emission of ICG in blood.

scholarly journals IRDye78 Conjugates for Near-Infrared Fluorescence Imaging

2002 ◽  
Vol 1 (4) ◽  
pp. 153535002002213
Author(s):  
Atif Zaheer ◽  
Thomas E. Wheat ◽  
John V. Frangioni
Keyword(s):  
Fluorescence Imaging ◽  
Near Infrared ◽  
Low Molecular Weight ◽  
Mass Ratio ◽  
Nir Fluorescence ◽  
Sample Purification ◽  
The Stability ◽  
Near Infrared Fluorescence Imaging ◽  
Neutral Conditions

The detection of human malignancies by near-infrared (NIR) fluorescence will require the conjugation of cancer-specific ligands to NIR fluorophores that have optimal photoproperties and pharmacokinetics. IRDye78, a tetra-sulfonated heptamethine indocyanine NIR fluorophore, meets most of the criteria for an in vivo imaging agent, and is available as an N-hydroxysuccinimide ester for conjugation to low-molecular-weight ligands. However, IRDye78 has a high charge-to-mass ratio, complicating purification of conjugates. It also has a potentially labile linkage between fluorophore and ligand. We have developed an ion-pairing purification strategy for IRDye78 that can be performed with a standard C18 column under neutral conditions, thus preserving the stability of fluorophore, ligand, and conjugate. By employing parallel evaporative light scatter and absorbance detectors, all reactants and products are identified, and conjugate purity is maximized. We describe reversible and irreversible conversions of IRDye78 that can occur during sample purification, and describe methods for preserving conjugate stability. Using seven ligands, spanning several classes of small molecules and peptides (neutral, charged, and/or hydrophobic), we illustrate the robustness of these methods, and confirm that IRDye78 conjugates so purified retain bioactivity and permit NIR fluorescence imaging of specific targets.

scholarly journals A non-intrusive evaluation method for tumor-targeting characteristics of nanomedicines based on in vivo near-infrared fluorescence imaging

2019 ◽  
Vol 7 (31) ◽  
pp. 4751-4757 ◽  
Author(s):  
Hao Liu ◽  
Rebecca T. Marquez ◽  
Xiaoqing Wu ◽  
Ke Li ◽  
Shweta Vadlamani ◽  
...  
Keyword(s):  
Fluorescence Imaging ◽  
Tumor Targeting ◽  
Near Infrared ◽  
Evaluation Method ◽  
Time Curve ◽  
Near Infrared Fluorescence ◽  
Nir Fluorescence ◽  
Near Infrared Fluorescence Imaging

A novel NIR fluorescence imaging-based method for non-intrusive evaluation of tumor targeting of nanomedicines was established. The average tumor-targeting index (TTI) and area under TTI-time curve (AUTC) were established as the in vivo indicators.

A novel near-infrared theranostic probe for accurate cancer chemotherapy in vivo by a dual activation strategy

2021 ◽  
Author(s):  
Wen-Xin Wang ◽  
Wen-Li Jiang ◽  
Guo-Jiang Mao ◽  
Zhi-Ke Tan ◽  
Min Tan ◽  
...  
Keyword(s):  
Drug Release ◽  
Fluorescence Imaging ◽  
Cancer Chemotherapy ◽  
Near Infrared ◽  
Nir Fluorescence ◽  
Dual Activation

A novel theranostic probe called CX-B-DF is constructed for chemotherapy guided by near-infrared (NIR) fluorescence imaging. Moreover, the accuracy of drug release is improved under dual activation (H2O2 and TP).

scholarly journals Targeted Nanoparticles for Fluorescence Imaging of Folate Receptor Positive Tumors

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1651
Author(s):  
Aimee J. Marko ◽  
Ballav M. Borah ◽  
Kevin E. Siters ◽  
Joseph R. Missert ◽  
Anurag Gupta ◽  
...  
Keyword(s):  
Folic Acid ◽  
Fluorescence Imaging ◽  
Near Infrared ◽  
Folate Receptor ◽  
Cyanine Dye ◽  
Target Specificity ◽  
Nir Fluorescence ◽  
Positive Breast Cancer

This report presents the synthesis and folate receptor target-specificity of amino-functionalized polyacrylamide nanoparticles (AFPAA NPs) for near-infrared (NIR) fluorescence imaging of cancer. For the synthesis of desired nano-constructs, the AFPAA NPs (hereafter referred to as NPs) were reacted with a NIR cyanine dye (CD) bearing carboxylic acid functionality by following our previously reported approach, and the resulting conjugate (NP-CD) on further reaction with folic acid (FA) resulted in a new nano-construct, FA-NP-CD, which demonstrated significantly higher uptake in folate receptor-positive breast cancer cells (KB+) and in folate receptor over-expressed tumors in vivo. The target-specificity of these nanoparticles was further confirmed by inhibition assay in folate receptor-positive (KB+) and -negative (HT-1080) cell lines. To show the advantages of polyacrylamide (PAA)-based NPs in folate receptor target-specificity, the CD used in preparing the FA-NP-CD construct was also reacted with folic acid alone and the synthetic conjugate (CD-FA) was also investigated for its target-specificity. Interestingly, in contrast to NPs (FA-NP-CD), the CD-FA conjugate did not show any significant in vitro or in vivo specificity toward folate receptors, showing the advantages of PAA-based nanotechnology in delivering the desired agent to tumor cells.

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