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
. 2019 Mar 15;9(15):8638-8649.
doi: 10.1039/c8ra10541c. eCollection 2019 Mar 12.

Fully automated peptide radiolabeling from [18F]fluoride

Ryan A Davis  1   2 , Chris Drake  3 , Robin C Ippisch  2 , Melissa Moore  3 , Julie L Sutcliffe  1   2   4
Affiliations

Fully automated peptide radiolabeling from [18F]fluoride

Ryan A Davis et al. RSC Adv. .

Abstract

The biological properties of receptor-targeted peptides have made them popular diagnostic imaging and therapeutic agents. Typically, the synthesis of fluorine-18 radiolabeled receptor-targeted peptides for positron emission tomography (PET) imaging is a time consuming, complex, multi-step synthetic process that is highly variable based on the peptide. The complexity associated with the radiolabeling route and lack of robust automated protocols can hinder translation into the clinic. A fully automated batch production to radiolabel three peptides (YGGFL, cRGDyK, and Pyr-QKLGNQWAVGHLM) from fluorine-18 using the ELIXYS FLEX/CHEM® radiosynthesizer in a two-step process is described. First, the prosthetic group, 6-[18F]fluoronicotinyl-2,3,5,6-tetrafluorophenyl ester ([18F]FPy-TFP) was synthesized and subsequently attached to the peptide. The [18F]FPy-peptides were synthesized in 13-26% decay corrected yields from fluorine-18 with high molar activity 1-5 Ci μmol-1 and radiochemical purity of >99% in an overall synthesis time of 97 ± 3 minutes.

PubMed Disclaimer

Conflict of interest statement

Drs Drake and Moore are employees and owners of SOFIE Co.

Figures

Fig. 1
Fig. 1. Structures of the target peptides.
Scheme 1
Scheme 1. (A) Radiolabeling of peptides with [18F]FPy-TFP (5). (B) Structures of radiolabeled [18F]FPy-peptides (6–8). Reagents and conditions: (a) [18F]F, K222, K2CO3, 4 : 1 tBuOH : MeCN, 40 °C, 10 min or (b) [18F]F, TBA-HCO3, 4 : 1 tBuOH : MeCN, 40 °C, 10 min. (c) Peptide (1 mg), DMSO, DIPEA, 40 °C, 15 min.
Fig. 2
Fig. 2. (A) ELIXYS FLEX/CHEM® radiosynthesizer (B) zoom-in of a reagent cassette above one of the reactors containing the v-vial.
Fig. 3
Fig. 3. Diagram of gross dilution set-up. Set-up allows [18F]FPy-TFP (5) purification via a 15 mL water dilution in an external flask, trapping on an Oasis MCX cartridge followed by a 5 mL water wash and 3 mL acetonitrile elution. All operations are fully automated via ELIXYS FLEX/CHEM® radiosynthesizer and no manual interventions required.
Fig. 4
Fig. 4. Mechanism for by-product (11) formation during [18F]FPy-TFP (5) synthesis.
Fig. 5
Fig. 5. [18F]FPy-TFP (5) HPLC-chromatograms (PMT (gamma)-red, UV (220 nm)-green). (A) Crude HPLC chromatogram (peak ●-6-[18F]fluoronicotinic acid, peak *-PyTFP-precursor (4), peak ■-2,3,5,6-tetrafluorophenol (9), peak ▲-[18F]FPy-TFP (5)). (B) HPLC chromatogram after MCX-cartridge purification (peak ●-6-[18F]fluoronicotinic acid, peak ■-2,3,5,6-tetrafluorophenol (9), peak ▲-[18F]FPy-TFP (5)). (C) HPLC chromatogram after MCX-C18SepPak double cartridge purification (peak ●-6-[18F]fluoronicotinic acid, peak ■-2,3,5,6-tetrafluorophenol (9), peak ▲-[18F]FPy-TFP (5)). (D) Purified HPLC-chromatogram co-injected with [19F]FPy-TFP (peak ▲-[18F]FPyTFP (5)).
Fig. 6
Fig. 6. HPLC chromatogram of radiolabeled [18F]FPy-YGGFL (6) (PMT(gamma)-red, UV(220 nm)-green). (A) Crude radioHPLC chromatogram (peak ●-6-[18F]fluoronicotinic acid, peak ♦-[18F]FPy-YGGFL (6)). (B) Purified HPLC chromatogram co-injected with [19F]FPy-YGGFL (peak ♦-[18F]FPy-YGGFL (6)).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kaspar A. A. Reichert J. M. Future directions for peptide therapeutics development. Drug Discovery Today. 2013;18(17):807–817. doi: 10.1016/j.drudis.2013.05.011. - DOI - PubMed
    1. Fosgerau K. Hoffmann T. Peptide therapeutics: current status and future directions. Drug Discovery Today. 2015;20(1):122–128. doi: 10.1016/j.drudis.2014.10.003. - DOI - PubMed
    1. Fani M. Maecke H. R. Okarvi S. M. Radiolabeled peptides: Valuable tools for the detection and treatment of cancer. Theranostics. 2012;2(5):481–501. doi: 10.7150/thno.4024. - DOI - PMC - PubMed
    1. Richter S. Wuest F. 18F-Labeled peptides: The future is bright. Molecules. 2014;19(12):20536–20556. doi: 10.3390/molecules191220536. - DOI - PMC - PubMed
    1. Hu L. Y. Kelly K. A. Sutcliffe J. L. High-throughput approaches to the development of molecular imaging agents. Mol. Imaging Biol. 2017;19(2):163–182. doi: 10.1007/s11307-016-1016-z. - DOI - PubMed