- 标题
- 摘要
- 关键词
- 实验方案
- 产品
-
Modular medical imaging agents based on azidea??alkyne Huisgen cycloadditions: Synthesis and prea??clinical evaluation of 18Fa??labeled PSMAa??tracers for prostate cancer imaging.
摘要： 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 preclinical in vivo evaluation of fluorine-18– labeled PSMA-targeting ‘F-PSMA-MIC’ radiotracers (t? = 109.7 min). Preclinical 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.
关键词： prostate specific membrane antigen,positron emission tomography,fluorine-18,azide-alkyne Huisgen cycloaddition,modular imaging agents
更新于2025-09-23 15:19:57
-
Synthesis of novel small-molecule fluorescently labeled probes for the in vitro imaging of KCa3.1 channels
摘要： In order to facilitate the in vitro visualization of KCa3.1 channel-expressing cells, novel small-molecule imaging probes were designed and developed. Senicapoc showing high affinity and excellent selectivity towards the KCa3.1 channels was selected as targeting component. Different BODIPY dyes (15 - 20) were synthesized and connected by a Cu-catalyzed azide alkyne [3+2]cycloaddition with propargyl ether derivative 8 of senicapoc yielding fluorescently labeled ligands 21 - 26 targeting KCa3.1 channels. The novel dimethylpyrrole-based imaging probes 25 and 26 allow staining of KCa3.1 ion channels in NSCLC cells following a simple, fast and efficient protocol. The specificity was shown by removing the punctate staining pattern by pre-incubation with senicapoc. The density of KCa3.1 channels detected with fluorescent probe 25 and by immunostaining was identical. The punctate structure of the labeled channels could be observed in living cells as well. Molecular modeling studies showed binding of the senicapoc targeting component towards the binding site within the ion channel and orientation of the linker with the dye along the inner surface of the ion channel.
关键词： labeled ligands,KCa3.1 channel,fluorescent probes,non-small cell lung cancer cells,molecular modelling,imaging agents,cycloaddition
更新于2025-09-23 15:19:57
-
Imaging of Tie2 with a Fluorescently Labeled Small Molecule Affinity Ligand
摘要： The receptor tyrosine kinase inhibitor, Tie2, has significant roles in endothelial signaling and angiogenesis, and is relevant in the pathophysiology of several diseases. However, there are relatively few small molecule probes available to study Tie2, making evaluation of its activity in vivo difficult. Recently, it was discovered that the small molecule, rebastinib (DCC-2036), is a potent Tie2 inhibitor. We hypothesized that fluorescent derivatives of rebastinib could be used as imaging agents for Tie2. Based on crystallography structures, we synthesized three fluorescent derivatives, which we then evaluated in both in vitro and in vivo assays. We found that the Rebastinib-BODIPY TMR (Reb-TMR) derivative has superior imaging characteristics in vitro, and successfully labeled endothelial cells in vivo. We propose that this probe could be further used in in vivo applications for studying the role of Tie2 in disease.
关键词： small molecule probes,rebastinib,Tie2,imaging agents,fluorescent derivatives,receptor tyrosine kinase,angiogenesis
更新于2025-09-12 10:27:22
-
Al <sup>18</sup> F-NODA Benzothiazole Derivatives as Imaging Agents for Cerebrovascular Amyloid in Cerebral Amyloid Angiopathy
摘要： In this study, we synthesized four novel Al18/19F-labeled 2-phenylbenzothiazole derivatives conjugated to 1,4,7-triazacyclononane-1,4-diacetic acid via alkyl linkers and evaluated them as imaging agent targets to amyloid-β (Aβ) plaques deposited in the blood vessels of cerebral amyloid angiopathy (CAA) brain. The four ligands exhibited moderate-to-high binding ability to Aβ1?42 aggregates, of which complex 17 possessing the most potent affinity (Ki = 11.3 nM) was selected for further biological evaluations. In vitro fluorescent staining and in vitro autoradiography studies on brain sections from CAA patients proved that this ligand could label Aβ deposits in blood vessels selectively. In biodistribution study, [18F]17 can hardly penetrate the blood?brain barrier (brain2 min = 0.3% ID/g) and displayed a rapid blood washout rate (blood2 min/blood60 min = 25.2), which is favorable as CAA imaging agents. In conclusion, this Al18F-labeled 2-phenylbenzothiazole complex was developed and proved to be a promising CAA positron emission tomography agent.
关键词： Al18F-NODA,cerebrovascular amyloid,benzothiazole derivatives,cerebral amyloid angiopathy,imaging agents
更新于2025-09-10 09:29:36
-
Perfluorocarbon‐Based <sup>19</sup> F?MRI Nanoprobes for In?Vivo Multicolor Imaging
摘要： In vivo multicolor imaging is important for monitoring multiple biomolecular or cellular processes in biology. 19F magnetic resonance imaging (MRI) is an emerging in vivo imaging technique because it can non-invasively visualize 19F nuclei without endogenous background signals. Therefore, 19F MRI probes capable of multicolor imaging are in high demand. Herein, we report five types of perfluorocarbon-encapsulated silica nanoparticles that show 19F NMR peaks with different chemical shifts. Three of the nanoprobes, which show spectrally distinct 19F NMR peaks with sufficient sensitivity, were selected for in vivo multicolor 19F MRI. The nanoprobes exhibited 19F MRI signals with three colors in a living mouse. Our in vivo multicolor system could be utilized for evaluating the effect of surface functional groups on the hepatic uptake in a mouse. This novel multicolor imaging technology will be a practical tool for elucidating in vivo biomolecular networks by 19F MRI.
关键词： multicolor imaging,fluorine,magnetic resonance imaging,nanoparticles,imaging agents
更新于2025-09-04 15:30:14