Synthesis and Monkey-PET Study of (R)- and (S)-18F-Labeled 2-Arylbenzoheterocyclic Derivatives as Amyloid Probes with Distinctive in Vivo Kinetics

Yang, Yanping; Wang, Xuedan; Yang, Hui; Fu, Hualong; Zhang, Jinming; Zhang, Xiaojun; Dai, Jiapei; Zhang, Zhiyong; Lin, Chunping; Guo, Yanbao; Cui, Mengchao

doi:10.1021/acs.molpharmaceut.6b00643

Cited by 14 publications

(12 citation statements)

References 37 publications

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“…In this synthesis, the resulting [ 18 F]5 radiolabeling agent was puri ed by distillation from the (Bruehlmeier et al 2004;Eschmann et al 2005); [18F]THK-5351 (Harada et al 2016;Tago et al 2016); [18F]FC1195S (Byun et al 2017;Lee et al 2016;Yang et al 2016);…”

Section: Resultsmentioning

confidence: 99%

“…Among these PET tracers, [ 18 F]FEDAA1106 (Fujimura et al 2006), [ 18 F]FE-SPARQ (Haneda et al 2007), [ 18 F]FMeNER-d 2 (Arakawa et al 2008), [ 18 F]FEPE2I (Sasaki et al 2012), and [ 18 F]FEDAC (Chung et al 2018;Xie et al 2012) have been synthesized for clinical applications in our PET center. (Bruehlmeier et al 2004;Eschmann et al 2005), [ 18 F]THK-5351 (Harada et al 2016;Tago et al 2016), [ 18 F]FC1195S (Byun et al 2017;Lee et al 2016;Yang et al 2016), [ 18 F]SMBT-1 (Harada et al 2021), and [ 18 F]PM-PBB3 (Tagai et al 2021) (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

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Automated radiosynthesis of two 18F-labeled tracers containing 3-fluoro-2-hydroxypropyl moiety, [18F]FMISO and [18F]PM-PBB3, via [18F]epifluorohydrin

Kawamura

Ohkubo

Kurihara

et al. 2021

Preprint

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Background [18F]Fluoromisonidazole ([18F]FMISO) and 1-[18F]fluoro-3-((2-((1E,3E)-4-(6-(methylamino)pyridine-3-yl)buta-1,3-dien-1-yl)benzo[d]thiazol-6-yl)oxy)propan-2-ol ([18F]PM-PBB3 or [18F]APN-1607) are clinically used radiotracers for imaging for hypoxia and tau pathology, respectively. Both radiotracers were produced by direct [18F]fluorination using the corresponding tosylate precursors 1 or 2 and [18F]F−, followed by the removal of protecting groups. In this study, we synthesized [18F]FMISO and [18F]PM-PBB3 by [18F]fluoroalkylation using [18F]epifluorohydrin ([18F]5) for clinical applications. Results First, [18F]5 was synthesized by the reaction of 1,2-epoxypropyl tosylate (8) with [18F]F− and was purified by distillation. Subsequently, [18F]5 was reacted with 2-nitroimidazole (6) or PBB3 (7) as a precursor for 18F-labeling, and each reaction mixture was refined by semipreparative high-performance liquid chromatography and formulation to obtain the [18F]FMISO or [18F]PM-PBB3 injection. All synthetic sequences were performed using an automated 18F-labeling synthesizer. The [18F]FMISO thus obtained showed sufficient radioactivity (0.83 ± 0.20 GBq at the end of synthesis; n = 8) with appropriate radiochemical yield based on [18F]F− (26 ± 7.5% at the end of irradiation with decay-corrected; n = 8). [18F]PM-PBB3 thus obtained showed sufficient radioactivity (0.79 ± 0.10 GBq; n = 11) with appropriate radiochemical yield based on [18F]F− (16 ± 3.2% at the end of irradiation with decay-corrected; n = 11). Conclusions Both [18F]FMISO and [18F]PM-PBB3 injections were successfully synthesized with sufficient radioactivity by [18F]fluoroalkylation using [18F]5.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Automated radiosynthesis of two 18F-labeled tracers containing 3-fluoro-2-hydroxypropyl moiety, [18F]FMISO and [18F]PM-PBB3, via [18F]epifluorohydrin

Kawamura

Ohkubo

Kurihara

et al. 2021

Preprint

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“…These ligands ( 1 – 4 ) have substituents, such as 2-(2-fluoroethoxy)ethoxy or 3-fluoro-2-hydroxypropoxy group at the para -position of one of the phenyl rings (Figs 2–4). These substituents have been introduced to radioligands for improvement of in vivo properties as well as radiolabeling with 18 F, as shown in the studies of radioligands for Aβ plaque imaging 18–20 .…”

Section: Discussionmentioning

confidence: 99%

“…As an alternative, we synthesized a precursor, which was obtained from several steps including the reaction with (±)-epichlorohydrin. However, the epoxide ring opening by n -Bu 4 N[ 18 F]F was not successful 20,21 . Therefore, a two-step reaction consisting of [ 18 F]fluorination of 10 , followed by aldol condensation with 8 was conducted and gave [ 18 F] 2 in relatively high yield (Fig.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and in vivo characterization of 18F-labeled difluoroboron-curcumin derivative for β-amyloid plaque imaging

Kim

Ahn

et al. 2019

Sci Rep

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Positron emission tomography imaging of β-amyloid (Aβ) plaques has proven useful in the diagnosis of Alzheimer’s disease. A previous study from our group showed that 4′- O -[ 18 F]fluoropropylcurcumin has poor brain permeability, which is thought to be due to its rapid metabolism. In this study, we synthesized difluoroboron complexes of fluorine-substituted curcumin derivatives ( 1 – 4 ) and selected one of them based on the in vitro binding assays. The selected ligand 2 was found to distinctively stain Aβ plaques in APP/PS1 transgenic mouse brain sections. Radioligand [ 18 F] 2 was synthesized via a two-step reaction consisting of [ 18 F]fluorination and subsequent aldol condensation. Biodistribution and metabolism studies indicated that radioligand [ 18 F] 2 was converted to polar radioactive products and trapped in the normal mouse brain. In contrast, optical images of mice acquired after injection of 2 showed moderate fluorescence signal intensity in the mouse brain at 2 min with a decrease in the signal within 30 min. In the ex vivo optical images, the fluorescence signals in major tissues disappeared within 30 min. Taken together, these results suggest that [ 18 F] 2 may be converted to polar 18 F-labeled blue-shifted fluorescent products. Further structural modifications are thus needed to render the radioligand metabolically stable.

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“…The 18 F-3-fluoro-2-hydroxypropyl ( 18 F-FHP) moiety was used instead of the aforementioned conventional 18 F-fluoroalkyl moieties. Many PET tracers containing the 18 F-FHP moiety have been developed, some of which have been used in clinical studies, such as [ 18 F]FMISO (Bruehlmeier et al 2004 ; Eschmann et al 2005 ), [ 18 F]THK-5351 (Harada et al 2016 ; Tago et al 2016 ), [ 18 F]FC1195S (Byun et al 2017 ; Lee et al 2016 ; Yang et al 2016 ), [ 18 F]SMBT-1 (Harada et al 2021 ), and [ 18 F]PM-PBB3 (Tagai et al 2021 ; Kawamura et al 2021 ) (Fig. 1 ).…”

Section: Introductionmentioning

confidence: 99%

Automated radiosynthesis of two 18F-labeled tracers containing 3-fluoro-2-hydroxypropyl moiety, [18F]FMISO and [18F]PM-PBB3, via [18F]epifluorohydrin

Ohkubo

Kurihara

Ogawa

et al. 2021

EJNMMI radiopharm. chem.

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Background [18F]Fluoromisonidazole ([18F]FMISO) and 1-[18F]fluoro-3-((2-((1E,3E)-4-(6-(methylamino)pyridine-3-yl)buta-1,3-dien-1-yl)benzo[d]thiazol-6-yl)oxy)propan-2-ol ([18F]PM-PBB3 or [18F]APN-1607) are clinically used radiotracers for imaging hypoxia and tau pathology, respectively. Both radiotracers were produced by direct 18F-fluorination using the corresponding tosylate precursors 1 or 2 and [18F]F−, followed by the removal of protecting groups. In this study, we synthesized [18F]FMISO and [18F]PM-PBB3 by 18F-fluoroalkylation using [18F]epifluorohydrin ([18F]5) for clinical applications. Results First, [18F]5 was synthesized by the reaction of 1,2-epoxypropyl tosylate (8) with [18F]F− and was purified by distillation. Subsequently, [18F]5 was reacted with 2-nitroimidazole (6) or PBB3 (7) as a precursor for 18F-labeling, and each reaction mixture was purified by preparative high-performance liquid chromatography and formulated to obtain the [18F]FMISO or [18F]PM-PBB3 injection. All synthetic sequences were performed using an automated 18F-labeling synthesizer. The obtained [18F]FMISO showed sufficient radioactivity (0.83 ± 0.20 GBq at the end of synthesis (EOS); n = 8) with appropriate radiochemical yield based on [18F]F− (26 ± 7.5 % at EOS, decay-corrected; n = 8). The obtained [18F]PM-PBB3 also showed sufficient radioactivity (0.79 ± 0.10 GBq at EOS; n = 11) with appropriate radiochemical yield based on [18F]F− (16 ± 3.2 % at EOS, decay-corrected; n = 11). Conclusions Both [18F]FMISO and [18F]PM-PBB3 injections were successfully synthesized with sufficient radioactivity by 18F-fluoroalkylation using [18F]5.

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Synthesis and Monkey-PET Study of (R)- and (S)-¹⁸F-Labeled 2-Arylbenzoheterocyclic Derivatives as Amyloid Probes with Distinctive in Vivo Kinetics

Cited by 14 publications

References 37 publications

Automated radiosynthesis of two 18F-labeled tracers containing 3-fluoro-2-hydroxypropyl moiety, [18F]FMISO and [18F]PM-PBB3, via [18F]epifluorohydrin

Automated radiosynthesis of two 18F-labeled tracers containing 3-fluoro-2-hydroxypropyl moiety, [18F]FMISO and [18F]PM-PBB3, via [18F]epifluorohydrin

Synthesis and in vivo characterization of 18F-labeled difluoroboron-curcumin derivative for β-amyloid plaque imaging

Automated radiosynthesis of two 18F-labeled tracers containing 3-fluoro-2-hydroxypropyl moiety, [18F]FMISO and [18F]PM-PBB3, via [18F]epifluorohydrin

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