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

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 ( 18 F) 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- 18 Ffluoronicotinic acid 4-nitrophenyl ester was conveniently prepared with an on-resin 18 F-fluorination in 29.9% radiochemical yield and 96.6% radiochemical purity. Interestingly, 6- 18 Ffluoronicotinic acid 4-nitrophenyl ester conjugated to ACooP exclusively by S -acylation instead of the expected N -acylation, and the chemical identity of the product 18 FFNA- S -ACooP was confirmed. In the in vitro binding experiments, 18 FFNA- 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 18 FFNA- S -ACooP binding specificity. Conclusions FABP3 targeted ACooP peptide was successfully radiolabeled by S -acylation using 6- 18 Ffluoronicotinic acid 4-nitrophenyl ester as the prosthetic compound. The tissue binding and blocking studies together with anti-FABP3 immunostaining confirmed 18 FFNA- S -ACooP binding specificity. Further preclinical studies of 18 FFNA- S -ACooP are warranted.