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. 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.

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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

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