scholarly journals Non-invasive In Vivo Fluorescence Optical Imaging of Inflammatory MMP Activity Using an Activatable Fluorescent Imaging Agent

Author(s):  
Johannes Schwenck ◽  
Florian C. Maier ◽  
Manfred Kneilling ◽  
Stefan Wiehr ◽  
Kerstin Fuchs
2012 ◽  
Author(s):  
Ruiwu Liu ◽  
Wenwu Xiao ◽  
Fernanda C. Bononi ◽  
Eduardo Sanchez ◽  
Yanlei Liu ◽  
...  

Theranostics ◽  
2017 ◽  
Vol 7 (13) ◽  
pp. 3369-3386 ◽  
Author(s):  
Marcel Miampamba ◽  
Junjie Liu ◽  
Alec Harootunian ◽  
Andrew J Gale ◽  
Stephen Baird ◽  
...  

2004 ◽  
Vol 13 (3) ◽  
pp. 166-175 ◽  
Author(s):  
Hideo Shichinohe ◽  
Satoshi Kuroda ◽  
Jang-Bo Lee ◽  
Goro Nishimura ◽  
Shunsuke Yano ◽  
...  

2020 ◽  
Author(s):  
Elahe Ganji ◽  
C. Savio Chan ◽  
Christopher W. Ward ◽  
Megan L. Killian

AbstractOptogenetics is an emerging alternative to traditional electrical stimulation to initiate action potentials in activatable cells both ex vivo and in vivo. Optogenetics has been commonly used in mammalian neurons and more recently, it has been adapted for activation of cardiomyocytes and skeletal muscle. Therefore, the aim of this study was to evaluate the stimulation feasibility and sustain isometric muscle contraction and limit decay for an extended period of time (1s), using non-invasive transdermal light activation of skeletal muscle (triceps surae) in vivo. We used inducible Cre recombination to target expression of Channelrhodopsin-2 (ChR2(H134R)-EYFP) in skeletal muscle (Acta1-Cre) in mice. Fluorescent imaging confirmed that ChR2 expression is localized in skeletal muscle and does not have specific expression in sciatic nerve branch, therefore, allowing for non-nerve mediated optical stimulation of skeletal muscle. We induced muscle contraction using transdermal exposure to blue light and selected 10Hz stimulation after controlled optimization experiments to sustain prolonged muscle contraction. Increasing the stimulation frequency from 10Hz to 40Hz increased the muscle contraction decay during prolonged 1s stimulation, highlighting frequency dependency and importance of membrane repolarization for effective light activation. Finally, we showed that optimized pulsed optogenetic stimulation of 10 Hz resulted in comparable ankle torque and contractile functionality to that of electrical stimulation. Our results demonstrate the feasibility and repeatability of non-invasive optogenetic stimulation of muscle in vivo and highlight optogenetic stimulation as a powerful tool for non-invasive in vivo direct activation of skeletal muscle.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3068-3068 ◽  
Author(s):  
Floris Jan Voskuil ◽  
Pieter Jan Steinkamp ◽  
Marjory Koller ◽  
Bert van der Vegt ◽  
Jan Johannes Doff ◽  
...  

3068 Background: ONM-100, a micelle-based polymer imaging agent conjugated to indocyanine green (ICG) and with an exquisitely pH-sensitive binary activation mechanism, may be used for tumor detection. ONM-100 micelles dissociate in acidic environments resulting in activation of the fluorescent ICG tag. As nearly all solid cancer types are acidotic, ONM-100 has the potential to act as a broadly indicated tumor agnostic imaging agent. This first-in-human study investigates the safety and feasibility of ONM-100 as a tumor agnostic imaging agent for intra-operative fluorescent imaging of various solid tumors. Methods: ONM-100 was IV administered 24±8h prior to surgery in a dose escalation scheme (0.1-1.2mg/kg). Patients with histopathologically confirmed breast cancer (BC), head and neck squamous cell carcinoma (HNSCC), colorectal cancer (CRC) and esophageal cancer (EC) were included. Blood was drawn to assess safety and pharmacokinetic data. Intra-operative fluorescence images were collected before and after tumor excision. Post-excision fluorescence images were obtained from serially sliced specimens and correlated with standard histopathological assessment. Results: 30 patients (11 BC, 13 HNSCC, 3 EC, 3 CRC) were enrolled. No ONM-100 related serious adverse events were observed and the agent was well-tolerated. A strong and sharply demarcated fluorescent signal was observed in all patients with vital tumor tissue (median CNR ranging 1.85-14.05) which correlated with tumor on final histopathology. HNSCC and superficially located BC as well as peritoneal metastasis could be clearly visualized in vivo during surgery. In four patients (BC and HNSCC), perioperatively, tumors otherwise unnoticed by the surgeons were detected on the margin or wound bed using fluorescence imaging. Additionally, two BC tumor lesions were detected that were missed by conventional pre-operative imaging and pathological assessment. Conclusions: ONM-100 appears to be safe and enables fluorescent visualization of tumors both in vivo and ex vivo. The first-in-human data demonstrate the feasibility for potential use of ONM-100 for image guided surgery, margin assessment and detection of occult disease. Clinical trial information: NTR 7085.


BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jennifer Bourn ◽  
Kusum Rathore ◽  
Robert Donnell ◽  
Wesley White ◽  
Md. Jashim Uddin ◽  
...  

Abstract Background Conventional cystoscopy can detect advanced stages of bladder cancer; however, it has limitations to detect bladder cancer at the early stages. Fluorocoxib A, a rhodamine-conjugated analog of indomethacin, is a novel fluorescent imaging agent that selectively targets cyclooxygenase-2 (COX-2)-expressing cancers. Methods In this study, we have used a carcinogen N-butyl-N-4-hydroxybutyl nitrosamine (BBN)-induced bladder cancer immunocompetent mouse B6D2F1 model that resembles human high-grade invasive urothelial carcinoma. We evaluated the ability of fluorocoxib A to detect the progression of carcinogen-induced bladder cancer in mice. Fluorocoxib A uptake by bladder tumors was detected ex vivo using IVIS optical imaging system and Cox-2 expression was confirmed by immunohistochemistry and western blotting analysis. After ex vivo imaging, the progression of bladder carcinogenesis from normal urothelium to hyperplasia, carcinoma-in-situ and carcinoma with increased Ki67 and decreased uroplakin-1A expression was confirmed by histology and immunohistochemistry analysis. Results The specific uptake of fluorocoxib A correlated with increased Cox-2 expression in progressing bladder cancer. In conclusion, fluorocoxib A detected the progression of bladder carcinogenesis in a mouse model with selective uptake in Cox-2-expressing bladder hyperplasia, CIS and carcinoma by 4- and 8-fold, respectively, as compared to normal bladder urothelium, where no fluorocoxib A was detected. Conclusions Fluorocoxib A is a targeted optical imaging agent that could be applied for the detection of Cox-2 expressing human bladder cancer.


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