383-50-6Relevant articles and documents
Radiosynthesis and preliminary evaluation of an 18F-labeled tubastatin A analog for PET imaging of histone deacetylase 6
Ishii, Kenji,Tago, Tetsuro,Toyohara, Jun
, (2019)
Histone deacetylase 6 (HDAC6) is a unique member of the HDAC family because of its characteristics, namely, its cytoplasmic localization and ubiquitin binding. HDAC6 has been implicated in cancer metastasis and neurodegeneration. In the present study, we performed radiosynthesis and biological evaluation of a fluorine-18–labeled ligand [18F]3, which is an analog of the HDAC6-selective inhibitor tubastatin A, for positron emission tomography (PET) imaging. [18F]3 was synthesized by a two-step reaction composed of 18F-fluorination and formation of a hydroxamic acid group. IC50 values of 3 against HDAC1 and HDAC6 activities were 996 nM and 33.1 nM, respectively. A biodistribution study in mice demonstrated low brain uptake of [18F]3. Furthermore, bone radioactivity was stable at around 2% ID/g after injection, suggesting high tolerance to defluorination. Regarding metabolic stability, 70% of the compound was observed as the unchanged form at 30 minutes post injection in mouse plasma. A small animal PET study in mice showed that pretreatment with cyclosporine A had no effect on initial brain uptake of [18F]3, suggesting low brain uptake of [18F]3 was not caused by the P-glycoprotein–mediated efflux. While PET imaging using [18F]3 has a limitation with respect to neurodegenerative diseases, further studies evaluating its utility for certain cancers are worth evaluating.
An unusual substitution reaction directed by an intramolecular re-arrangement
Parenty, Alexis D.C.,Smith, Louise V.,Cronin, Leroy
, p. 8410 - 8418 (2005)
Secondary amines and thiols undertake a substitution reaction on the side chain of 2-bromoethyl-pyridinium derivatives 'directed' by an intramolecular re-arrangement. Experimental investigations strongly indicate that the reaction is initiated by an alpha
Radiosynthesis of [18F]DPA-714, a selective radioligand for imaging the translocator protein (18 kDa) with PET
Damont, Annelaure,Hinnen, Francoise,Kuhnast, Bertrand,Schoellhorn-Peyronneau, Marie-Anne,James, Michelle,Luus, Christopher,Tavitian, Bertrand,Kassiou, Michael,Dolle, Frederic
, p. 286 - 292 (2008)
Recently, a novel series of 2-phenylpyrazolo[1,5-α] pyrimidineacetamides has been reported as selective ligands of the translocator protein (18 kDa). Within this series, DPA-714 (N,N-diethyl-2-(2-(4-(2- fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-α]pyri
Synthesis and biological evaluation of PET tracers designed for imaging of calcium activated potassium channel 3.1 (KCa3.1) channels: In vivo
B?rgel, Frederik,Br?mmel, Kathrin,Budde, Thomas,Bulk, Etmar,Konken, Christian Paul,Obeng-Darko, Henry,Sch?fers, Michael,Schelhaas, Sonja,Schwab, Albrecht,Wünsch, Bernhard
, p. 30295 - 30304 (2021/10/25)
Expression of the Ca2+ activated potassium channel 3.1 (KCa3.1) channel (also known as the Gàrdos channel) is dysregulated in many tumor entities and has predictive power with respect to patient survival. Therefore, a positron emission tomography (PET) tracer targeting this ion channel could serve as a potential diagnostic tool by imaging the KCa3.1 channel in vivo. It was envisaged to synthesize [18F]senicapoc ([18F]1) since senicapoc (1) shows high affinity and excellent selectivity towards the KCa3.1 channels. Because problems occurred during 18F-fluorination, the [18F]fluoroethoxy senicapoc derivative [18F]28 was synthesized to generate an alternative PET tracer targeting the KCa3.1 channel. Inhibition of the KCa3.1 channel by 28 was confirmed by patch clamp experiments. In vitro stability in mouse and human serum was shown for 28. Furthermore, biodistribution experiments in wild type mice were performed. Since [18F]fluoride was detected in vivo after application of [18F]28, an in vitro metabolism study was conducted. A potential degradation route of fluoroethoxy derivatives in vivo was found which in general should be taken into account when designing new PET tracers for different targets with a [18F]fluoroethoxy moiety as well as when using the popular prosthetic group [18F]fluoroethyl tosylate for the alkylation of phenols.
Development of Novel 18F-PET Agents for Tumor Hypoxia Imaging
Wang, Li,Wang, Hui,Shen, Kun,Park, Hyejin,Zhang, Tao,Wu, Xuedan,Hu, Mei,Yuan, Hong,Chen, Yue,Wu, Zhanhong,Wang, Qiu,Li, Zibo
, p. 5593 - 5602 (2021/05/31)
Tumor hypoxia is a major factor responsible for tumor progression, metastasis, invasion, and treatment resistance, leading to low local tumor control and recurrence after radiotherapy in cancers. Here,18F-positron emission tomography (PET) probes are developed for visualizing viable hypoxic cells in biopsies. Pimonidazole derivatives and nitroimidazole-based agents bearing sulfonyl linkers were evaluated. A small-animal PET study showed that the tumor uptake of [18F]-23 [poly(ethylene glycols) (PEG)-sulfonyl linker] of 3.36 ± 0.29%ID/g was significantly higher (P 0.01) than that of [18F]-20 (piperazine-linker tracer, 2.55 ± 0.49%ID/g) at 2 h postinjection in UPPL tumors. The tumor-to-muscle uptake ratio of [18F]-23 (2.46 ± 0.48 at 2 h pi) was well improved compared with that of [18F]-FMISO (1.25 ± 0.14 at 2 h pi). A comparable distribution pattern was observed between ex vivo autoradiography of [18F]-23 and pimonidazole staining of the neighboring slice, indicating that [18F]-23 is a promising PET agent for hypoxia imaging.