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.
| Original language | English |
|---|---|
| Article number | 16 |
| Pages (from-to) | 16 |
| Journal | EJNMMI Radiopharmacy and Chemistry |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 23 Feb 2024 |
| MoE publication type | A1 Journal article-refereed |
Funding
Tissue staining was digitized using a 3DHISTECH Pannoramic 250 FLASH II slide scanner at the Genome Biology Unit supported by HiLIFE and the Faculty of Medicine, University of Helsinki and Biocenter Finland. Mass spectrometry analyses were performed at the Turku Proteomics Facility supported by Biocenter Finland. H&E staining was performed at the Histocore unit, University of Turku. NMR analysis was performed in Turku Centre for Chemical and Molecular Analytics, Åbo Akademi University and Univeristy of Turku, Turku, Finland. We thank the research grants from the Finnish Cancer Foundation, the Finnish Cultural Foundation, the Turku University Foundation, Turku University Hospital and Sigrid Jusélius Foundation. This research was partially supported by the Research Council of Finland’s Flagship InFLAMES and the funding Decision Numbers were 337530 and 357910.