scholarly journals Target-responsive vasoactive probes for ultrasensitive molecular imaging

2019 ◽  
Author(s):  
Robert Ohlendorf ◽  
Agata Wiśniowska ◽  
Mitul Desai ◽  
Ali Barandov ◽  
Adrian L. Slusarczyk ◽  
...  

ABSTRACTThe ability to monitor molecules volumetrically throughout the body could provide valuable biomarkers for studies of healthy function and disease, but noninvasive detection of molecular targets in living subjects often suffers from poor sensitivity or selectivity. Here we describe a family of potent imaging probes that can be activated by molecules of interest in deep tissue, providing a basis for mapping nanomolar-scale analytes without the radiation or heavy metal content associated with traditional molecular imaging agents. The probes are reversibly-caged vasodilators that induce responses detectable by hemodynamic imaging; they are constructed by combining vasoactive peptides with synthetic chemical appendages and protein blocking domains. We use this architecture to create ultrasensitive biotin-responsive imaging agents, which we apply for wide-field mapping of targets in rat brains using functional magnetic resonance imaging. We also adapt the sensor design for detecting the neurotransmitter dopamine, illustrating versatility of this approach for addressing biologically important molecules.

2016 ◽  
Vol 33 (6) ◽  
pp. 761-800 ◽  
Author(s):  
C. L. Charron ◽  
J. L. Hickey ◽  
T. K. Nsiama ◽  
D. R. Cruickshank ◽  
W. L. Turnbull ◽  
...  

Natural peptides possess a unique target specificity for their endogenous receptor that allows them to be exploited as diagnostic and therapeutic agents. This has led to the discovery and derivatization of various natural peptides into molecular imaging agents.


2020 ◽  
Vol 13 (8) ◽  
pp. 199
Author(s):  
Joseph Lau ◽  
Julie Rousseau ◽  
Daniel Kwon ◽  
François Bénard ◽  
Kuo-Shyan Lin

Kinins, bradykinin and kallidin are vasoactive peptides that signal through the bradykinin B1 and B2 receptors (B1R and B2R). B2R is constitutively expressed in healthy tissues and mediates responses such as vasodilation, fluid balance and retention, smooth muscle contraction, and algesia, while B1R is absent in normal tissues and is induced by tissue trauma or inflammation. B2R is activated by kinins, while B1R is activated by kinins that lack the C-terminal arginine residue. Perturbations of the kinin system have been implicated in inflammation, chronic pain, vasculopathy, neuropathy, obesity, diabetes, and cancer. In general, excess activation and signaling of the kinin system lead to a pro-inflammatory state. Depending on the disease context, agonism or antagonism of the bradykinin receptors have been considered as therapeutic options. In this review, we summarize molecular imaging agents targeting these G protein-coupled receptors, including optical and radioactive probes that have been used to interrogate B1R/B2R expression at the cellular and anatomical levels, respectively. Several of these preclinical agents, described herein, have the potential to guide therapeutic interventions for these receptors.


2016 ◽  
Vol 57 (10) ◽  
pp. 1583-1590 ◽  
Author(s):  
N. P. Withana ◽  
T. Saito ◽  
X. Ma ◽  
M. Garland ◽  
C. Liu ◽  
...  

2012 ◽  
Vol 13 (12) ◽  
pp. 16986-17005 ◽  
Author(s):  
Sung Kim ◽  
Mitsuru Hattori ◽  
Takeaki Ozawa

2017 ◽  
Vol 25 (3) ◽  
pp. 1163-1171 ◽  
Author(s):  
Victoria Calzada ◽  
María Moreno ◽  
Jessica Newton ◽  
Joel González ◽  
Marcelo Fernández ◽  
...  

Author(s):  
Eva M. Sevick-Muraca ◽  
Banghe Zhu ◽  
Barrett R. Harvey ◽  
Mary A. Hall ◽  
Kenneth L. Pinkston ◽  
...  

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