Radiosynthesis of a carbon-11 labeled tetrahydrobenzisoxazole derivative as a new PET probe for γ-secretase imaging in Alzheimer's disease

Zhidong Xu, Caihong Miao, Fugui Dong, Limeng Jia, Wei Li, Min Wang, Wenqing Liu, Qi Huang Zheng

Research output: Contribution to journalArticle

Abstract

To develop PET radiotracers for imaging of Alzheimer's disease, a new carbon-11 labeled potent and selective γ-secretase modulator (GSM) has been synthesized. The reference standard tetrahydrobenzisoxazole derivative 8 and its desmethylated precursor 9 were synthesized from cyclohex-2-en-1-one and 3-hydroxy-4-nitrobenzaldehyde in eight and nine steps with 11% and 5% overall chemical yield, respectively. The radiotracer [11C]8 was prepared from its corresponding precursor 9 with [11C]CH3OTf through O–11C-methylation and isolated by RP-HPLC combined with SPE in 45–50% radiochemical yield, based on [11C]CO2 and decay corrected to EOB. The radiochemical purity was >99%, and the molar activity (Am) at EOB was 555–740 GBq/μmol.

Original languageEnglish (US)
Article number108915
JournalApplied Radiation and Isotopes
Volume155
DOIs
StatePublished - Jan 2020

Fingerprint

Radioactive tracers
Positron emission tomography
Methylation
alkylation
Alkylation
Global system for mobile communications
Modulators
Derivatives
Imaging techniques
Carbon
methylation
probes
carbon
modulators
purity
decay

Keywords

  • Alzheimer's disease (AD)
  • Carbon-11 labeled γ-secretase modulator (GSM)
  • Positron emission tomography (PET)
  • Radiosynthesis
  • γ-Secretase

ASJC Scopus subject areas

  • Radiation

Cite this

Radiosynthesis of a carbon-11 labeled tetrahydrobenzisoxazole derivative as a new PET probe for γ-secretase imaging in Alzheimer's disease. / Xu, Zhidong; Miao, Caihong; Dong, Fugui; Jia, Limeng; Li, Wei; Wang, Min; Liu, Wenqing; Zheng, Qi Huang.

In: Applied Radiation and Isotopes, Vol. 155, 108915, 01.2020.

Research output: Contribution to journalArticle

@article{e70dcdba4fcc4f05846a6a32c40848ba,
title = "Radiosynthesis of a carbon-11 labeled tetrahydrobenzisoxazole derivative as a new PET probe for γ-secretase imaging in Alzheimer's disease",
abstract = "To develop PET radiotracers for imaging of Alzheimer's disease, a new carbon-11 labeled potent and selective γ-secretase modulator (GSM) has been synthesized. The reference standard tetrahydrobenzisoxazole derivative 8 and its desmethylated precursor 9 were synthesized from cyclohex-2-en-1-one and 3-hydroxy-4-nitrobenzaldehyde in eight and nine steps with 11{\%} and 5{\%} overall chemical yield, respectively. The radiotracer [11C]8 was prepared from its corresponding precursor 9 with [11C]CH3OTf through O–11C-methylation and isolated by RP-HPLC combined with SPE in 45–50{\%} radiochemical yield, based on [11C]CO2 and decay corrected to EOB. The radiochemical purity was >99{\%}, and the molar activity (Am) at EOB was 555–740 GBq/μmol.",
keywords = "Alzheimer's disease (AD), Carbon-11 labeled γ-secretase modulator (GSM), Positron emission tomography (PET), Radiosynthesis, γ-Secretase",
author = "Zhidong Xu and Caihong Miao and Fugui Dong and Limeng Jia and Wei Li and Min Wang and Wenqing Liu and Zheng, {Qi Huang}",
year = "2020",
month = "1",
doi = "10.1016/j.apradiso.2019.108915",
language = "English (US)",
volume = "155",
journal = "Applied Radiation and Isotopes",
issn = "0969-8043",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Radiosynthesis of a carbon-11 labeled tetrahydrobenzisoxazole derivative as a new PET probe for γ-secretase imaging in Alzheimer's disease

AU - Xu, Zhidong

AU - Miao, Caihong

AU - Dong, Fugui

AU - Jia, Limeng

AU - Li, Wei

AU - Wang, Min

AU - Liu, Wenqing

AU - Zheng, Qi Huang

PY - 2020/1

Y1 - 2020/1

N2 - To develop PET radiotracers for imaging of Alzheimer's disease, a new carbon-11 labeled potent and selective γ-secretase modulator (GSM) has been synthesized. The reference standard tetrahydrobenzisoxazole derivative 8 and its desmethylated precursor 9 were synthesized from cyclohex-2-en-1-one and 3-hydroxy-4-nitrobenzaldehyde in eight and nine steps with 11% and 5% overall chemical yield, respectively. The radiotracer [11C]8 was prepared from its corresponding precursor 9 with [11C]CH3OTf through O–11C-methylation and isolated by RP-HPLC combined with SPE in 45–50% radiochemical yield, based on [11C]CO2 and decay corrected to EOB. The radiochemical purity was >99%, and the molar activity (Am) at EOB was 555–740 GBq/μmol.

AB - To develop PET radiotracers for imaging of Alzheimer's disease, a new carbon-11 labeled potent and selective γ-secretase modulator (GSM) has been synthesized. The reference standard tetrahydrobenzisoxazole derivative 8 and its desmethylated precursor 9 were synthesized from cyclohex-2-en-1-one and 3-hydroxy-4-nitrobenzaldehyde in eight and nine steps with 11% and 5% overall chemical yield, respectively. The radiotracer [11C]8 was prepared from its corresponding precursor 9 with [11C]CH3OTf through O–11C-methylation and isolated by RP-HPLC combined with SPE in 45–50% radiochemical yield, based on [11C]CO2 and decay corrected to EOB. The radiochemical purity was >99%, and the molar activity (Am) at EOB was 555–740 GBq/μmol.

KW - Alzheimer's disease (AD)

KW - Carbon-11 labeled γ-secretase modulator (GSM)

KW - Positron emission tomography (PET)

KW - Radiosynthesis

KW - γ-Secretase

UR - http://www.scopus.com/inward/record.url?scp=85072794987&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072794987&partnerID=8YFLogxK

U2 - 10.1016/j.apradiso.2019.108915

DO - 10.1016/j.apradiso.2019.108915

M3 - Article

C2 - 31590101

AN - SCOPUS:85072794987

VL - 155

JO - Applied Radiation and Isotopes

JF - Applied Radiation and Isotopes

SN - 0969-8043

M1 - 108915

ER -