A Highly Selective Low-Background Fluorescent Imaging Agent for Nitric Oxide

2010 ◽  
Vol 132 (38) ◽  
pp. 13114-13116 ◽  
Author(s):  
Youjun Yang ◽  
Stephanie K. Seidlits ◽  
Michelle M. Adams ◽  
Vincent M. Lynch ◽  
Christine E. Schmidt ◽  
...  
Theranostics ◽  
2017 ◽  
Vol 7 (13) ◽  
pp. 3369-3386 ◽  
Author(s):  
Marcel Miampamba ◽  
Junjie Liu ◽  
Alec Harootunian ◽  
Andrew J Gale ◽  
Stephen Baird ◽  
...  

Talanta ◽  
2013 ◽  
Vol 117 ◽  
pp. 196-202 ◽  
Author(s):  
Ye-Yun Zhang ◽  
Ming Wu ◽  
Yan-Qin Wang ◽  
Xi-Wen He ◽  
Wen-You Li ◽  
...  

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.


2016 ◽  
Vol 104 ◽  
pp. 226-234 ◽  
Author(s):  
Eva J. ter Weele ◽  
Anton G.T. Terwisscha van Scheltinga ◽  
Matthijs D. Linssen ◽  
Wouter B. Nagengast ◽  
Ingo Lindner ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4340
Author(s):  
Mikhail Panfilov ◽  
Darya Chernova ◽  
Irina Khalfina ◽  
Alexander Moskalensky ◽  
Aleksey Vorob’ev

Nitric oxide (NO) is an important signaling molecule involved in a wide range of physiological and pathological processes. Fluorescent imaging is a useful tool for monitoring NO concentration, which could be essential in various biological and biochemical studies. Here, we report the design of a novel small-molecule fluorescent probe based on 9(10H)acridone moiety for nitric oxide sensing. 7,8-Diamino-4-carboxy-10-methyl-9(10H)acridone reacts with NO in aqueous media in the presence of O2, yielding a corresponding triazole derivative with fivefold increased fluorescence intensity. The probe was shown to be capable of nitric oxide sensing in living Jurkat cells.


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