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
. 2024 Feb 23;9(1):16.
doi: 10.1186/s41181-024-00245-3.

Radiosynthesis, structural identification and in vitro tissue binding study of [18F]FNA-S-ACooP, a novel radiopeptide for targeted PET imaging of fatty acid binding protein 3

Pyry Dillemuth #  1 , Tuomas Karskela #  1 , Abiodun Ayo  2 , Jesse Ponkamo  1 , Jonne Kunnas  1   3 , Johan Rajander  4 , Olli Tynninen  5 , Anne Roivainen  6   7   8 , Pirjo Laakkonen  2   9   10 , Anu J Airaksinen  1 , Xiang-Guo Li  11   12   13
Affiliations

Radiosynthesis, structural identification and in vitro tissue binding study of [18F]FNA-S-ACooP, a novel radiopeptide for targeted PET imaging of fatty acid binding protein 3

Pyry Dillemuth et al. EJNMMI Radiopharm Chem. .

Abstract

Background: Fatty acid binding protein 3 (FABP3) is a target with clinical relevance and the peptide ligand ACooP has been identified for FABP3 targeting. ACooP is a linear decapeptide containing a free amino and thiol group, which provides opportunities for conjugation. This work is to develop methods for radiolabeling of ACooP with fluorine-18 (18F) for positron emission tomography (PET) applications, and evaluate the binding of the radiolabeled ACooP in human tumor tissue sections with high FABP3 expression.

Results: The prosthetic compound 6-[18F]fluoronicotinic acid 4-nitrophenyl ester was conveniently prepared with an on-resin 18F-fluorination in 29.9% radiochemical yield and 96.6% radiochemical purity. Interestingly, 6-[18F]fluoronicotinic acid 4-nitrophenyl ester conjugated to ACooP exclusively by S-acylation instead of the expected N-acylation, and the chemical identity of the product [18F]FNA-S-ACooP was confirmed. In the in vitro binding experiments, [18F]FNA-S-ACooP exhibited heterogeneous and high focal binding in malignant tissue sections, where we also observed abundant FABP3 positivity by immunofluorescence staining. Blocking study further confirmed the [18F]FNA-S-ACooP binding specificity.

Conclusions: FABP3 targeted ACooP peptide was successfully radiolabeled by S-acylation using 6-[18F]fluoronicotinic acid 4-nitrophenyl ester as the prosthetic compound. The tissue binding and blocking studies together with anti-FABP3 immunostaining confirmed [18F]FNA-S-ACooP binding specificity. Further preclinical studies of [18F]FNA-S-ACooP are warranted.

Keywords: ACooP; Autoradiography; Fatty acid binding protein 3; Fluorine-18; PET; Peptide; Peptide radiolabeling; S-acylation.

PubMed Disclaimer

Conflict of interest statement

XGL is an Editorial Board member of EJNMMI Radiopharmacy and Chemistry. Other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Examples of 18F-prosthetic groups for N-acylation of biomolecules
Fig. 2
Fig. 2
Radiosynthesis of [18F]FNA-S-ACooP
Fig. 3
Fig. 3
Identification and quality control of [18F]FNA-S-ACooP. HPLC chromatograms of [18F]FNA-S-ACooP under radioactivity detection (A) and reference compound FNA-N-ACooP (B) and [18F]FNA-S-ACooP (C) under UV detection
Fig. 4:
Fig. 4:
1H NMR spectra of FNA-N-ACooP and FNA-S-ACooP
Fig. 5
Fig. 5
In vitro binding studies of [18F]FNA-S-ACooP in brain metastasis tissue sections from a patient with lung cancer. A Autoradiography, B immunofluorescence, C histology of adjacent sections. Left panels: whole tissue section; middle and right panels: high-power views of the areas within the red or black rectangles
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Basuli F, Zhang X, Jagoda EM, Choyke P, Swenson RE. Facile room temperature synthesis of fluorine-18 labeled fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester without azeotropic drying of fluorine-18. Nucl Med Biol. 2016;43:770–772. doi: 10.1016/j.nucmedbio.2016.08.008. - DOI - PMC - PubMed
    1. Basuli F, Zhang X, Phelps TE, Jagoda EM, Choyke PL, Swenson RE. Automated synthesis of fluorine-18 labeled CXCR4 ligand via the conjugation with nicotinic acid N-hydroxysuccinimide ester (6-[18F]SFPy) Molecules. 2020;25:3924. doi: 10.3390/molecules25173924. - DOI - PMC - PubMed
    1. Feng XX, Gao T, Kang D, Jiang D, Yao J, Jing Y, et al. Mammary-derived growth inhibitor-modified PEG-PLA nanoparticles for enhanced targeted glioblastoma therapy. Bioconjug Chem. 2015;26:1850–1861. doi: 10.1021/acs.bioconjchem.5b00379. - DOI - PubMed
    1. Haskali MB, Farnsworth AL, Roselt PD, Hutton CA. 4-Nitrophenyl activated esters are superior synthons for indirect radiofluorination of biomolecules. RSC Med Chem. 2020;11:919–922. doi: 10.1039/D0MD00140F. - DOI - PMC - PubMed
    1. Hyvönen M, Enbäck J, Huhtala T, Lammi J, Sihto H, Weisell J, et al. Novel target for peptide-based imaging and treatment of brain tumors. Mol Cancer Ther. 2014;13:996–1007. doi: 10.1158/1535-7163.MCT-13-0684. - DOI - PMC - PubMed

LinkOut - more resources