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Title: Synthesis of Diverse 11C-Labeled PET Radiotracers via Direct Incorporation of [11C]CO2

Abstract

Three new positron emission tomography (PET) radiotracers of interest to our functional neuroimaging and translational oncology programs have been prepared through new developments in [11C]CO2 fixation chemistry. [11C]QZ (glutaminyl cyclase) was prepared via a tandem trapping of [11C]CO2/intramolecular cyclization; [11C]tideglusib (glycogen synthase kinase-3) was synthesized through a tandem trapping of [11C]CO2 followed by an intermolecular cycloaddition between a [11C]isocyanate and an isothiocyanate to form the 1,2,4-thiadiazolidine-3,5-dione core; [11C]ibrutinib (Bruton’s tyrosine kinase) was synthesized through a HATU peptide coupling of an amino precursor with [11C]acrylic acid (generated from [11C]CO2 fixation with vinylmagnesium bromide). All radiochemical syntheses are fully-automated on commercial radiochemical synthesis modules and provide radiotracers in 1 – 5% radiochemical yield (non-corrected, based upon [11C]CO2). In addition, all three radiotracers have advanced to rodent imaging studies and preliminary PET imaging results are also reported.

Authors:
 [1];  [1];  [1];  [1];  [1];  [2];  [2];  [3];  [1]
  1. Univ. of Michigan Medical School, Ann Arbor, MI (United States). Division of Nuclear Medicine and Dept. of Radiology
  2. Bristol-Myers Squibb Research and Development, Princeton, NJ (United States). Discovery Chemistry Platforms and PET Radiochemical Synthesis
  3. Univ. of Michigan Medical School, Ann Arbor, MI (United States). The Interdepartmental Program in Medicinal Chemistry, Division of Nuclear Medicine and Dept. of Radiology
Publication Date:
Research Org.:
Univ. of Michigan Medical School, Ann Arbor, MI (United States)
Sponsoring Org.:
USDOE; National Institutes of Health (NIH); Alzheimer’s Association
OSTI Identifier:
1467011
Grant/Contract Number:  
SC0012484; T32-EB005172; NIRP-14-305669
Resource Type:
Accepted Manuscript
Journal Name:
Bioconjugate Chemistry
Additional Journal Information:
Journal Volume: 27; Journal Issue: 5; Journal ID: ISSN 1043-1802
Publisher:
American Chemical Society
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

Mossine, Andrew V., Brooks, Allen F., Jackson, Isaac M., Quesada, Carole A., Sherman, Phillip, Cole, Erin L., Donnelly, David J., Scott, Peter J. H., and Shao, Xia. Synthesis of Diverse 11C-Labeled PET Radiotracers via Direct Incorporation of [11C]CO2. United States: N. p., 2016. Web. doi:10.1021/acs.bioconjchem.6b00163.
Mossine, Andrew V., Brooks, Allen F., Jackson, Isaac M., Quesada, Carole A., Sherman, Phillip, Cole, Erin L., Donnelly, David J., Scott, Peter J. H., & Shao, Xia. Synthesis of Diverse 11C-Labeled PET Radiotracers via Direct Incorporation of [11C]CO2. United States. doi:10.1021/acs.bioconjchem.6b00163.
Mossine, Andrew V., Brooks, Allen F., Jackson, Isaac M., Quesada, Carole A., Sherman, Phillip, Cole, Erin L., Donnelly, David J., Scott, Peter J. H., and Shao, Xia. Mon . "Synthesis of Diverse 11C-Labeled PET Radiotracers via Direct Incorporation of [11C]CO2". United States. doi:10.1021/acs.bioconjchem.6b00163. https://www.osti.gov/servlets/purl/1467011.
@article{osti_1467011,
title = {Synthesis of Diverse 11C-Labeled PET Radiotracers via Direct Incorporation of [11C]CO2},
author = {Mossine, Andrew V. and Brooks, Allen F. and Jackson, Isaac M. and Quesada, Carole A. and Sherman, Phillip and Cole, Erin L. and Donnelly, David J. and Scott, Peter J. H. and Shao, Xia},
abstractNote = {Three new positron emission tomography (PET) radiotracers of interest to our functional neuroimaging and translational oncology programs have been prepared through new developments in [11C]CO2 fixation chemistry. [11C]QZ (glutaminyl cyclase) was prepared via a tandem trapping of [11C]CO2/intramolecular cyclization; [11C]tideglusib (glycogen synthase kinase-3) was synthesized through a tandem trapping of [11C]CO2 followed by an intermolecular cycloaddition between a [11C]isocyanate and an isothiocyanate to form the 1,2,4-thiadiazolidine-3,5-dione core; [11C]ibrutinib (Bruton’s tyrosine kinase) was synthesized through a HATU peptide coupling of an amino precursor with [11C]acrylic acid (generated from [11C]CO2 fixation with vinylmagnesium bromide). All radiochemical syntheses are fully-automated on commercial radiochemical synthesis modules and provide radiotracers in 1 – 5% radiochemical yield (non-corrected, based upon [11C]CO2). In addition, all three radiotracers have advanced to rodent imaging studies and preliminary PET imaging results are also reported.},
doi = {10.1021/acs.bioconjchem.6b00163},
journal = {Bioconjugate Chemistry},
number = 5,
volume = 27,
place = {United States},
year = {2016},
month = {4}
}

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Works referencing / citing this record:

Recent progress in [ 11 C]carbon dioxide ([ 11 C]CO 2 ) and [ 11 C]carbon monoxide ([ 11 C]CO) chemistry
journal, February 2018

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