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
Review
. 2017 Nov 7;23(62):15553-15577.
doi: 10.1002/chem.201701581. Epub 2017 Sep 1.

18 F-Labeling of Sensitive Biomolecules for Positron Emission Tomography

Hema S Krishnan  1 , Longle Ma  1 , Neil Vasdev  1 , Steven H Liang  1
Affiliations
Review

18 F-Labeling of Sensitive Biomolecules for Positron Emission Tomography

Hema S Krishnan et al. Chemistry. .

Abstract

Positron emission tomography (PET) imaging study of fluorine-18 labeled biomolecules is an emerging and rapidly growing area for preclinical and clinical research. The present review focuses on recent advances in radiochemical methods for incorporating fluorine-18 into biomolecules via "direct" or "indirect" bioconjugation. Recently developed prosthetic groups and pre-targeting strategies, as well as representative examples in 18 F-labeling of biomolecules in PET imaging research studies are highlighted.

Keywords: bioconjugation; biomolecules; click chemistry; fluorine-18; positron emission tomography.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Direct18F-Labeling Through C–18F Bond Formation. Radiochemical conversion, RCC; radiochemical yield, RCY.
Figure 2
Figure 2
Direct18F-Labeling Through Aziridine Ring-Opening and C–18F Bond Formation.
Figure 3
Figure 3
Biocatalytic [18F]Fluorination of Peptide Using Fluorinase.
Figure 4
Figure 4
Direct 18F-Labeling Through B–18F Bond Formation.
Figure 5
Figure 5. Direct 18F-Labeling Through 19F–18F Isotope Exchange
Figure 6
Figure 6
Direct 18F-Labeling Through Si–18F Bond Formation.
Figure 7
Figure 7
Direct 18F-Labeling Through Al–18F Chelation.
Figure 8
Figure 8. Examples of NH2-selective 18F-Prosthetic Groups
Figure 9
Figure 9
Fluorine-18 Containing Prosthetic Groups for Oxime Formation.
Figure 10
Figure 10. Fluorine-18 labeling of Biomolecules involving Oxime Formation
Figure 11
Figure 11
Fluorine-18 labeling of Biomolecules using [18F]Fluorosugars.
Figure 12
Figure 12
Thiol-selective Prosthetic Groups.
Figure 13
Figure 13. Fluorine-18 Labeling Methods Involving Sulfur-containing Prosthetic Groups
Figure 14
Figure 14. Recent Thiol-Selective Fluorine-18 Radiolabeling
Figure 15
Figure 15
Cyanobenzothiazole Prosthetic Groups for Fluorine-18 labeling of Cysteine-containing Biomolecules.
Figure 16
Figure 16
Fluorine-18 Labeling via X-Csp2Bond Formation with Prosthetic Groups.
Figure 17
Figure 17
Fluorine-18 Labeled Alkyne Building Blocks.
Figure 18
Figure 18
Fluorine-18 Labeling of Biomolecules via CuAAC Between Azide Containing Biomolecules and Labeled Alkynes.
Figure 19
Figure 19
A) Synthesis of [18F]FEA;B) Examples of Radiotracers Synthesized with [18F]FEA Building Block; C) Some Representative Fluorine-18 labeled Azides in Click Chemistry.
Figure 20
Figure 20
Fluorine-18 Radiolabeling of Biomolecules via Spirocyclic Iodonium Ylides.
Figure 21
Figure 21
Silicon–18F Based Building Block for Biomolecule Labeling via CuAAC.
Figure 22
Figure 22. Fluorine-18 Labeled ADIBO Prosthetic Groups for SPAAC
Figure 23
Figure 23
Fluorine-18 Labeling of Azide-Terminated Peptide Containing PEG Linker via SPAAC.
Figure 24
Figure 24
Alkyne-ADIBO Building Block for Fluorine-18 Labeling of Biomolecules.
Figure 25
Figure 25
Traceless Staudinger Ligation to Radiolabel Biomolecules.
Figure 26
Figure 26
Synthesis of Fluorine-18 Labeled Amino Acid Derivatives from Diarylphosphine Based Thioesters.
Figure 27
Figure 27
A) Synthesis of Fluorine-18 Labeled TCO, [18F]16. B) Fluorine-18 Labeling of Cyclic-RGD peptide via Tetrazine Ligation.
Figure 28
Figure 28
Comparison of Fluorine-18 Labeling by Tetrazine Ligation and Conventional Labeling Strategies.
Figure 29
Figure 29
A Fluorine-18 labeled PEG-TCO Prosthetic Group with Improved Pharmacokinetics.
Figure 30
Figure 30
Bioconjugation through Tetrazine-Alkyne IEDDA Reactions.
Figure 31
Figure 31
Synthesis of Fluorine-18 Labeled Tetrazine Building Blocks.
Figure 32
Figure 32
Radiolabeling of TCO-terminated Biomolecules in vivo with Fluorine-18 Labeled Tetrazine Building Blocks.
Figure 33
Figure 33
[3+2] Cycloaddition of Dipolarophiles with 4-[18F]Fluorobenzonitrile Oxide.
See this image and copyright information in PMC

References

    1. Ametamey SM, Honer M, Schubiger PA. Chem Rev. 2008;108:1501–1516. - PubMed
    1. Gambhir SS. J Nucl Med. 2006;47:557–558. - PubMed
    2. Jacobson O, Chen X. Pharmacol Rev. 2013;65:1214–1256. - PMC - PubMed
    3. Kuhnast B, de Bruin B, Hinnen F, Tavitian B, Dollé F. Bioconjugate Chem. 2004;15:617–627. - PubMed
    4. Shi H, He X, Wang K, Wu X, Ye X, Guo Q, Tan W, Qing Z, Yang X, Zhou B. Proc Natl Acad Sci. 2011;108:3900–3905. - PMC - PubMed
    5. Vaidyanathan G, Zalutsky MR. Nucl Med Biol. 1997;24:171–178. - PubMed
    6. Wester HJ, Hamacher K, Stöcklin G. Nucl Med Biol. 1996;23:365–372. - PubMed
    7. Kühnast B, Dollé F, Terrazzino S, Rousseau B, Loc'h C, Vaufrey F, Hinnen F, Doignon I, Pillon F, David C. Bioconjugate Chem. 2000;11:627–636. - PubMed
    1. Hoffman JM, Gambhir SS. Radiology. 2007;244:39–47. - PubMed
    2. Adam MJ, Wilbur DS. Chem Soc Rev. 2005;34:153–163. - PubMed
    3. Mankoff DA, Eary JF, Link JM, Muzi M, Rajendran JG, Spence AM, Krohn KA. Clin Cancer Res. 2007;13:3460–3469. - PubMed
    1. Fowler JS, Wolf AP. Acc Chem Res. 1997;30:181–188.
    1. Phelps ME. Proc Natl Acad Sci. 2000;97:9226–9233. - PMC - PubMed