232597-42-1Relevant articles and documents
Near-Infrared Photoactivatable Nitric Oxide Donors with Integrated Photoacoustic Monitoring
Zhou, Effie Y.,Knox, Hailey J.,Reinhardt, Christopher J.,Partipilo, Gina,Nilges, Mark J.,Chan, Jefferson
, p. 11686 - 11697 (2018)
Photoacoustic (PA) tomography is a noninvasive technology that utilizes near-infrared (NIR) excitation and ultrasonic detection to image biological tissue at centimeter depths. While several activatable small-molecule PA sensors have been developed for various analytes, the use of PA molecules for deep-tissue analyte delivery and monitoring remains an underexplored area of research. Herein, we describe the synthesis, characterization, and in vivo validation of photoNOD-1 and photoNOD-2, the first organic, NIR-photocontrolled nitric oxide (NO) donors that incorporate a PA readout of analyte release. These molecules consist of an aza-BODIPY dye appended with an aryl N-nitrosamine NO-donating moiety. The photoNODs exhibit chemostability to various biological stimuli, including redox-active metals and CYP450 enzymes, and demonstrate negligible cytotoxicity in the absence of irradiation. Upon single-photon NIR irradiation, photoNOD-1 and photoNOD-2 release NO as well as rNOD-1 or rNOD-2, PA-active products that enable ratiometric monitoring of NO release. Our in vitro studies show that, upon irradiation, photoNOD-1 and photoNOD-2 exhibit 46.6-fold and 21.5-fold ratiometric turn-ons, respectively. Moreover, unlike existing NIR NO donors, the photoNODs do not require encapsulation or multiphoton activation for use in live animals. In this study, we use PA tomography to monitor the local, irradiation-dependent release of NO from photoNOD-1 and photoNOD-2 in mice after subcutaneous treatment. In addition, we use a murine model for breast cancer to show that photoNOD-1 can selectively affect tumor growth rates in the presence of NIR light stimulation following systemic administration.
11C Radiolabeling of anle253b: a Putative PET Tracer for Parkinson's Disease That Binds to α-Synuclein Fibrils in vitro and Crosses the Blood-Brain Barrier
Bender, Dirk,Buss, Sabrina,Giese, Armin,Griesinger, Christian,Herfert, Kristina,Kuebler, Laura,Leonov, Andrei,Linder, Ruth,Maurer, Andreas,Pichler, Bernd J.,Ryazanov, Sergey,Schmidt, Felix,Weckbecker, Daniel
, (2020)
There is an urgent clinical need for imaging of α-synuclein (αSyn) fibrils, the hallmark biomarker for Parkinson's disease, in neurodegenerative disorders. Despite immense efforts, promising tracer candidates for nuclear imaging of αSyn are rare. Diphenyl pyrazoles are known modulators of αSyn aggregation and thus bear potential for non-invasive detection of this biomarker in vivo. Here we demonstrate high-affinity binding of the family member anle253b to fibrillar αSyn and present a high-yielding site-selective radiosynthesis route for 11C radiolabeling using in-situ generated [11C]formaldehyde and reductive methylation. Radio-HPLC of the tracer after incubation with rat serum in vitro shows excellent stability of the molecule. Positron emission tomography in healthy animals is used to assess the pharmacokinetics and biodistribution of the tracer, showing good penetration of the blood–brain barrier and low background binding to the non-pathological brain.
Near-infrared photoactivatable nitric oxide donors with photoacoustic readout
Zhou, Effie Y.,Knox, Hailey J.,Reinhardt, Christopher J.,Partipilo, Gina,Chan, Jefferson
, p. 113 - 147 (2020/06/27)
In this chapter, we motivate the need for photoactivatable NO donor molecules and give a brief survey of the existing chemical tools in the field. We then provide detailed protocols for the synthesis and validation of a near-infrared light-activated NO do
