scholarly journals Responsive Trimodal Probes for In Vivo Imaging of Liver Inflammation by Coassembly and GSH-Driven Disassembly

Research ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Yuxuan Hu ◽  
Yuqi Wang ◽  
Xidan Wen ◽  
Yifan Pan ◽  
Xiaoyang Cheng ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Fluorescence Imaging ◽  
In Vivo Imaging ◽  
Ex Vivo ◽  
Molecular Probes ◽  
Liver Inflammation ◽  
Diagnosis And Prognosis ◽  
Imaging Probes ◽  
Substantial Decline

Noninvasive in vivo imaging of hepatic glutathione (GSH) levels is essential to early diagnosis and prognosis of acute hepatitis. Although GSH-responsive fluorescence imaging probes have been reported for evaluation of hepatitis conditions, the low penetration depth of light in liver tissue has impeded reliable GSH visualization in the human liver. We present a liver-targeted and GSH-responsive trimodal probe (GdNPs-Gal) for rapid evaluation of lipopolysaccharide- (LPS-) induced acute liver inflammation via noninvasive, real-time in vivo imaging of hepatic GSH depletion. GdNPs-Gal are formed by molecular coassembly of a GSH-responsive Gd(III)-based MRI probe (1-Gd) and a liver-targeted probe (1-Gal) at a mole ratio of 5/1 (1-Gd/1-Gal), which shows high r1 relaxivity with low fluorescence and fluorine magnetic resonance spectroscopic (19F-MRS) signals. Upon interaction with GSH, 1-Gd and 1-Gal are cleaved and GdNPs-Gal rapidly disassemble into small molecules 2-Gd, 2-Gal, and 3, producing a substantial decline in r1 relaxivity with compensatory enhancements in fluorescence and 19F-MRS. By combining in vivo magnetic resonance imaging (1H-MRI) with ex vivo fluorescence imaging and 19F-MRS analysis, GdNPs-Gal efficiently detect hepatic GSH using three independent modalities. We noninvasively visualized LPS-induced liver inflammation and longitudinally monitored its remediation in mice after treatment with an anti-inflammatory drug, dexamethasone (DEX). Findings highlight the potential of GdNPs-Gal for in vivo imaging of liver inflammation by integrating molecular coassembly with GSH-driven disassembly, which can be applied to other responsive molecular probes for improved in vivo imaging.

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.

Biomimetic magnetofluorescent ferritin nanoclusters for magnetic resonance and fluorescence-dual modal imaging and targeted tumor therapy

2021 ◽  
Author(s):  
Rongguang Song ◽  
Jian Dai Dai ◽  
Miaoliang Ruan ◽  
Wei Xue
Keyword(s):  
Magnetic Resonance ◽  
Fluorescence Imaging ◽  
In Vivo Imaging ◽  
Tumor Therapy ◽  
Multiple Imaging

Multiple imaging by combing magnetic resonance (MR) and fluorescence imaging into a single nanosystem displays distinctive merits, which is desirable for precise in vivo imaging. In this work, we proposed...

scholarly journals Site-Specific Dual-Labeling of a VHH with a Chelator and a Photosensitizer for Nuclear Imaging and Targeted Photodynamic Therapy of EGFR-Positive Tumors

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 428
Author(s):  
Emma Renard ◽  
Estel Collado Camps ◽  
Coline Canovas ◽  
Annemarie Kip ◽  
Martin Gotthardt ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Fluorescence Imaging ◽  
Ex Vivo ◽  
Growth Factor Receptor ◽  
Nuclear Imaging ◽  
A431 Cells ◽  
Site Specific ◽  
Variable Domains ◽  
Diagnostic Probe

Variable domains of heavy chain only antibodies (VHHs) are valuable agents for application in tumor theranostics upon conjugation to both a diagnostic probe and a therapeutic compound. Here, we optimized site-specific conjugation of the chelator DTPA and the photosensitizer IRDye700DX to anti-epidermal growth factor receptor (EGFR) VHH 7D12, for applications in nuclear imaging and photodynamic therapy. 7D12 was site-specifically equipped with bimodal probe DTPA-tetrazine-IRDye700DX using the dichlorotetrazine conjugation platform. Binding, internalization and light-induced toxicity of DTPA-IRDye700DX-7D12 were determined using EGFR-overexpressing A431 cells. Finally, ex vivo biodistribution of DTPA-IRDye700DX-7D12 in A431 tumor-bearing mice was performed, and tumor homing was visualized with SPECT and fluorescence imaging. DTPA-IRDye700DX-7D12 was retrieved with a protein recovery of 43%, and a degree of labeling of 0.56. Spectral properties of the IRDye700DX were retained upon conjugation. 111In-labeled DTPA-IRDye700DX-7D12 bound specifically to A431 cells, and they were effectively killed upon illumination. DTPA-IRDye700DX-7D12 homed to A431 xenografts in vivo, and this could be visualized with both SPECT and fluorescence imaging. In conclusion, the dichlorotetrazine platform offers a feasible method for site-specific dual-labeling of VHH 7D12, retaining binding affinity and therapeutic efficacy. The flexibility of the described approach makes it easy to vary the nature of the probes for other combinations of diagnostic and therapeutic compounds.

scholarly journals GFP-Aequorin Protein Sensor for Ex Vivo and In Vivo Imaging of Ca 2+ Dynamics in High-Ca 2+ Organelles

2016 ◽  
Vol 23 (6) ◽  
pp. 738-745 ◽  
Author(s):  
Paloma Navas-Navarro ◽  
Jonathan Rojo-Ruiz ◽  
Macarena Rodriguez-Prados ◽  
María Dolores Ganfornina ◽  
Loren L. Looger ◽  
...  
Keyword(s):  
In Vivo Imaging ◽  
Ex Vivo ◽  
Protein Sensor

scholarly journals BIMG-08. DEUTERIUM MAGNETIC RESONANCE SPECTROSCOPY USING 2H-PYRUVATE ALLOWS NON-INVASIVE IN VIVO IMAGING OF TERT EXPRESSION IN BRAIN TUMORS

2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i2-i2
Author(s):  
Georgios Batsios ◽  
Celine Taglang ◽  
Meryssa Tran ◽  
Anne Marie Gillespie ◽  
Joseph Costello ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
In Vivo Imaging ◽  
Lactate Production ◽  
Telomere Maintenance ◽  
Resonance Spectroscopy ◽  
Low Grade ◽  
Non Invasive ◽  
Tert Expression

Abstract Telomere shortening constitutes a natural barrier to uncontrolled proliferation and all tumors must find a mechanism of maintaining telomere length. Most human tumors, including high-grade primary glioblastomas (GBMs) and low-grade oligodendrogliomas (LGOGs) achieve telomere maintenance via reactivation of the expression of telomerase reverse transcriptase (TERT), which is silenced in normal somatic cells. TERT expression is, therefore, a driver of tumor proliferation and, due to this essential role, TERT is also a therapeutic target. However, non-invasive methods of imaging TERT are lacking. The goal of this study was to identify magnetic resonance spectroscopy (MRS)-detectable metabolic biomarkers of TERT expression that will enable non-invasive visualization of tumor burden in LGOGs and GBMs. First, we silenced TERT expression by RNA interference in patient-derived LGOG (SF10417, BT88) and GBM (GS2) models. Our results linked TERT silencing to significant reductions in steady-state levels of NADH in all models. NADH is essential for the conversion of pyruvate to lactate, suggesting that measuring pyruvate flux to lactate could be useful for imaging TERT status. Recently, deuterium (2H)-MRS has emerged as a novel, clinically translatable method of monitoring metabolic fluxes in vivo. However, to date, studies have solely examined 2H-glucose and the use of [U-2H]pyruvate for non-invasive 2H-MRS has not been tested. Following intravenous injection of a bolus of [U-2H]pyruvate, lactate production was higher in mice bearing orthotopic LGOG (BT88 and SF10417) and GBM (GS2) tumor xenografts relative to tumor-free mice, suggesting that [U-2H]pyruvate has the potential to monitor TERT expression in vivo. In summary, our study, for the first time, shows the feasibility and utility of [U-2H]pyruvate for in vivo imaging. Importantly, since 2H-MRS can be implemented on clinical scanners, our results provide a novel, non-invasive method of integrating information regarding a fundamental cancer hallmark, i.e. TERT, into glioma patient management.

scholarly journals Ex Vivo and In Vivo Imaging and Biodistribution of Aptamers Targeting the Human Matrix MetalloProtease-9 in Melanomas

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0149387 ◽  
Author(s):  
David Kryza ◽  
Frédéric Debordeaux ◽  
Laurent Azéma ◽  
Aref Hassan ◽  
Olivier Paurelle ◽  
...  
Keyword(s):  
In Vivo Imaging ◽  
Ex Vivo ◽  
Matrix Metalloprotease

Ex vivo measurement of tissue distribution of a nitroxide radical after intravenous injection and its in vivo imaging using a rapid scan ESR-CT system

2000 ◽  
Vol 18 (2) ◽  
pp. 151-156 ◽  
Author(s):  
Hitoshi Togashi ◽  
Taku Matsuo ◽  
Haruhide Shinzawa ◽  
Yoshio Takeda ◽  
Li Shao ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Intravenous Injection ◽  
In Vivo Imaging ◽  
Ex Vivo ◽  
Nitroxide Radical ◽  
Rapid Scan ◽  
Ct System

scholarly journals In Vivo Imaging of Peripheral Benzodiazepine Receptors in Mouse Lungs: A Biomarker of Inflammation

2005 ◽  
Vol 4 (4) ◽  
pp. 7290.2005.05133 ◽  
Author(s):  
Matthew J. Hardwick ◽  
Ming-Kai Chen ◽  
Kwamena Baidoo ◽  
Martin G. Pomper ◽  
Tomás R. Guilarte
Keyword(s):  
In Vivo Imaging ◽  
Ex Vivo ◽  
Inflammatory Diseases ◽  
Imaging Techniques ◽  
Benzodiazepine Receptors ◽  
Small Animal ◽  
Small Animal Pet ◽  
Planar Imaging ◽  
Peripheral Benzodiazepine Receptors

The ability to visualize the immune response with radioligands targeted to immune cells will enhance our understanding of cellular responses in inflammatory diseases. Peripheral benzodiazepine receptors (PBR) are present in monocytes and neutrophils as well as in lung tissue. We used lipopolysaccharide (LPS) as a model of inflammation to assess whether the PBR could be used as a noninvasive marker of inflammation in the lungs. Planar imaging of mice administrated 10 or 30 mg/kg LPS showed increased [123I]-( R)-PK11195 radioactivity in the thorax 2 days after LPS treatment relative to control. Following imaging, lungs from control and LPS-treated mice were harvested for ex vivo gamma counting and showed significantly increased radioactivity above control levels. The specificity of the PBR response was determined using a blocking dose of nonradioactive PK11195 given 30 min prior to radiotracer injection. Static planar images of the thorax of nonradioactive PK11195 pretreated animals showed a significantly lower level of radiotracer accumulation in control and in LPS-treated animals ( p < .05). These data show that LPS induces specific increases in PBR ligand binding in the lungs. We also used in vivo small-animal PET studies to demonstrate increased [11C]-( R)-PK11195 accumulation in the lungs of LPS-treated mice. This study suggests that measuring PBR expression using in vivo imaging techniques may be a useful biomarker to image lung inflammation.

scholarly journals Dynamic, Simultaneous Concentration Mapping of Multiple MRI Contrast Agents with Dual Contrast - Magnetic Resonance Fingerprinting

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Christian E. Anderson ◽  
Mette Johansen ◽  
Bernadette O. Erokwu ◽  
He Hu ◽  
Yuning Gu ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Contrast Agents ◽  
Ex Vivo ◽  
Single Agent ◽  
Mri Contrast Agents ◽  
Mri Contrast Agent ◽  
Spatiotemporal Resolution ◽  
Mri Contrast ◽  
Contrast Magnetic Resonance

AbstractSynchronous assessment of multiple MRI contrast agents in a single scanning session would provide a new “multi-color” imaging capability similar to fluorescence imaging but with high spatiotemporal resolution and unlimited imaging depth. This multi-agent MRI technology would enable a whole new class of basic science and clinical MRI experiments that simultaneously explore multiple physiologic/molecular events in vivo. Unfortunately, conventional MRI acquisition techniques are only capable of detecting and quantifying one paramagnetic MRI contrast agent at a time. Herein, the Dual Contrast – Magnetic Resonance Fingerprinting (DC-MRF) methodology was extended for in vivo application and evaluated by simultaneously and dynamically mapping the intra-tumoral concentration of two MRI contrast agents (Gd-BOPTA and Dy-DOTA-azide) in a mouse glioma model. Co-registered gadolinium and dysprosium concentration maps were generated with sub-millimeter spatial resolution and acquired dynamically with just over 2-minute temporal resolution. Mean tumor Gd and Dy concentration measurements from both single agent and dual agent DC-MRF studies demonstrated significant correlations with ex vivo mass spectrometry elemental analyses. This initial in vivo study demonstrates the potential for DC-MRF to provide a useful dual-agent MRI platform.

scholarly journals In vivo imaging techniques: a new era for histochemical analysis

2016 ◽  
Author(s):  
A. Busato ◽  
P. Fumene Feruglio ◽  
P.P. Parnigotto ◽  
P. Marzola ◽  
A. Sbarbati
Keyword(s):  
Magnetic Resonance ◽  
In Vivo Imaging ◽  
Diffusion Tensor ◽  
Technological Development ◽  
Imaging Techniques ◽  
Resonance Spectroscopy ◽  
Preclinical Research ◽  
Tissue Contrast ◽  
Magnetic Resonance Imaging Mri

In vivo imaging techniques can be integrated with classical histochemistry to create an actual histochemistry of water. In particular, Magnetic Resonance Imaging (MRI), an imaging technique primarily used as diagnostic tool in clinical/preclinical research, has excellent anatomical resolution, unlimited penetration depth and intrinsic soft tissue contrast. Thanks to the technological development, MRI is not only capable to provide morphological information but also and more interestingly functional, biophysical and molecular. In this paper we describe the main features of several advanced imaging techniques, such as MRI microscopy, Magnetic Resonance Spectroscopy, functional MRI, Diffusion Tensor Imaging and MRI with contrast agent as a useful support to classical histochemistry.

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