916687-71-3Relevant academic research and scientific papers
Modular Medical Imaging Agents Based on Azide–Alkyne Huisgen Cycloadditions: Synthesis and Pre-Clinical Evaluation of 18F-Labeled PSMA-Tracers for Prostate Cancer Imaging
B?hmer, Verena I.,Szymanski, Wiktor,van den Berg, Keimpe-Oeds,Mulder, Chantal,Kobauri, Piermichele,Helbert, Hugo,van der Born, Dion,Reeβing, Friederike,Huizing, Anja,Klopstra, Marten,Samplonius, Douwe F.,Antunes, Ines F.,Sijbesma, Jürgen W. A.,Luurtsema, Gert,Helfrich, Wijnand,Visser, Ton J.,Feringa, Ben L.,Elsinga, Philip H.
, p. 10871 - 10881 (2020)
Since the seminal contribution of Rolf Huisgen to develop the [3+2] cycloaddition of 1,3-dipolar compounds, its azide–alkyne variant has established itself as the key step in numerous organic syntheses and bioorthogonal processes in materials science and chemical biology. In the present study, the copper(I)-catalyzed azide–alkyne cycloaddition was applied for the development of a modular molecular platform for medical imaging of the prostate-specific membrane antigen (PSMA), using positron emission tomography. This process is shown from molecular design, through synthesis automation and in vitro studies, all the way to pre-clinical in vivo evaluation of fluorine-18- labeled PSMA-targeting ‘F-PSMA-MIC’ radiotracers (t1/2=109.7 min). Pre-clinical data indicate that the modular PSMA-scaffold has similar binding affinity and imaging properties to the clinically used [68Ga]PSMA-11. Furthermore, we demonstrated that targeting the arene-binding in PSMA, facilitated through the [3+2]cycloaddition, can improve binding affinity, which was rationalized by molecular modeling. The here presented PSMA-binding scaffold potentially facilitates easy coupling to other medical imaging moieties, enabling future developments of new modular imaging agents.
Chemical Targeting of Voltage Sensitive Dyes to Specific Cells and Molecules in the Brain
Fiala, Tomas,Wang, Jihang,Dunn, Matthew,?ebej, Peter,Choi, Se Joon,Nwadibia, Ekeoma C.,Fialova, Eva,Martinez, Diana M.,Cheetham, Claire E.,Fogle, Keri J.,Palladino, Michael J.,Freyberg, Zachary,Sulzer, David,Sames, Dalibor
, p. 9285 - 9301 (2020/06/04)
Voltage sensitive fluorescent dyes (VSDs) are important tools for probing signal transduction in neurons and other excitable cells. The impact of these highly lipophilic sensors has, however, been limited due to the lack of cell-specific targeting methods in brain tissue or living animals. We address this key challenge by introducing a nongenetic molecular platform for cell- and molecule-specific targeting of synthetic VSDs in the brain. We employ a dextran polymer particle to overcome the inherent lipophilicity of VSDs by dynamic encapsulation and high-affinity ligands to target the construct to specific neuronal cells utilizing only native components of the neurotransmission machinery at physiological expression levels. Dichloropane, a monoamine transporter ligand, enables targeting of dense dopaminergic axons in the mouse striatum and sparse noradrenergic axons in the mouse cortex in acute brain slices. PFQX in conjunction with ligand-directed acyl imidazole chemistry enables covalent labeling of AMPA-type glutamate receptors in the same brain regions. Probe variants bearing either a classical electrochromic ANEP dye or state-of-the-art VoltageFluor-type dye respond to membrane potential changes in a similar manner to the parent dyes, as shown by whole-cell patch recording. We demonstrate the feasibility of optical voltage recording with our probes in brain tissue with one-photon and two-photon fluorescence microscopy and define the signal limits of optical voltage imaging with synthetic sensors under a low photon budget determined by the native expression levels of the target proteins. This work demonstrates the feasibility of a chemical targeting approach and expands the possibilities of cell-specific imaging and pharmacology.
PROCESS FOR PRODUCING RADIOHALOGENATED BIOCONJUGATES AND PRODUCTS THEREOF
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Paragraph 0265; 0266, (2013/08/28)
The present invention relates to a new synthetic process in which an alkyne and an azide react to form a radioisotopic bioconjugate construct. The reaction is particularly useful for producing compounds for use in imaging and radiotherapy applications. The present invention also provides bioconjugate labels and further relates to the use of these compounds in diagnostic and therapeutic methods. In addition, the invention provides a related process for introducing a radioisotopic halogen atom into a terminal alkyne.
One-pot synthesis of an 125I-labeled trifunctional reagent for multiscale imaging with optical and nuclear techniques
Yan, Ran,El-Emir, Ethaar,Rajkumar, Vineeth,Robson, Mathew,Jathoul, Amit P.,Pedley, R. Barbara,Arstad, Erik
supporting information; experimental part, p. 6793 - 6795 (2011/09/13)
A highly efficient and rapid CuII-mediated three-component "click reaction" allows one-pot assembly of dual optical and nuclear labeling reagents. Proof-of-concept imaging studies demonstrate that the distribution of the dual-labeled antibody A
