Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jul 16;27(40):10369-10376.
doi: 10.1002/chem.202100690. Epub 2021 Jun 2.

Broad Scope and High-Yield Access to Unsymmetrical Acyclic [11 C]Ureas for Biomedical Imaging from [11 C]Carbonyl Difluoride

Jimmy E Jakobsson  1 , Sanjay Telu  1 , Shuiyu Lu  1 , Susovan Jana  1 , Victor W Pike  1
Affiliations

Broad Scope and High-Yield Access to Unsymmetrical Acyclic [11 C]Ureas for Biomedical Imaging from [11 C]Carbonyl Difluoride

Jimmy E Jakobsson et al. Chemistry. .

Abstract

Effective methods are needed for labelling acyclic ureas with carbon-11 (t1/2 =20.4 min) as potential radiotracers for biomedical imaging with positron emission tomography (PET). Herein, we describe the rapid and high-yield syntheses of unsymmetrical acyclic [11 C]ureas under mild conditions (room temperature and within 7 min) using no-carrier-added [11 C]carbonyl difluoride with aliphatic and aryl amines. This methodology is compatible with diverse functionality (e. g., hydroxy, carboxyl, amino, amido, or pyridyl) in the substrate amines. The labelling process proceeds through putative [11 C]carbamoyl fluorides and for primary amines through isolable [11 C]isocyanate intermediates. Unsymmetrical [11 C]ureas are produced with negligible amounts of unwanted symmetrical [11 C]urea byproducts. Moreover, the overall labelling method tolerates trace water and the generally moderate to excellent yields show good reproducibility. [11 C]Carbonyl difluoride shows exceptional promise for application to the synthesis of acyclic [11 C]ureas as new radiotracers for biomedical imaging with PET.

Keywords: [11C]carbonyl difluoride; carbon 11; positron emission tomography; radiochemistry; ureas.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest

The authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
Comparison of prominent methods for the synthesis of acyclic [11C]ureas from amines.
See this image and copyright information in PMC

References

    1. Phelps ME, Proc. Natl. Acad. Sci. USA 2000, 97, 9226–9233. - PMC - PubMed
    1. Chua S, Groves A, Biomedical imaging: applications and advances, Elsevier, Cambridge, Waltham, 2014, p. 3–40;
    2. Heurling K, Leuzy A, Jonasson M, Frick A, Zimmer ER, Nordberg A, Lubberink M, Brain Res. 2017, 1670, 220–234; - PubMed
    3. Villemagne VL, Doré V, Burnham SC, Masters CL, Rowe CC, Nat. Rev. Neurol. 2018, 14, 225–236; - PubMed
    4. Slifstein M, Abi-Dargham A, Semin. Nucl. Med. 2017, 47, 54–63. - PubMed
    1. Herholz K, Heiss WD, Mol. Imaging Biol. 2004, 6, 239–269; - PubMed
    2. Gallamini A, Zwarthoed C, Borra A, Cancers (Basel). 2014, 6, 1821–1889. - PMC - PubMed
    1. McCluskey SP, Plisson C, Rabiner EA, Howes O, Eur. J. Nucl. Med. Mol. Imaging 2019, 47, 451–489; - PMC - PubMed
    2. Matthews PM, Rabiner EA, Passchier J, Gunn RN, Br. J. Clin. Pharmacol. 2011, 73, 175–186. - PMC - PubMed
    1. Ametamey SM, Honer M, Schubiger PA, Chem. Rev. 2008, 108, 1501–1516; - PubMed
    2. Pike VW, Curr. Med. Chem. 2016, 23, 1818–1869; - PMC - PubMed
    3. Lu S, Simeon FB, Telu S, Cai L, Pike VW, The Chemistry of labelling heterocycles with carbon-11 and fluorine-18 for biomedical imaging, Advances in Heterocyclic Chemistry, volume 132, Scriven EFV, Ramsden CA (eds), Academic Press, Cambridge, 2020, p 241–384.

LinkOut - more resources