Switching the Chemoselectivity in the Preparation of [18F]FNA-N-CooP, a Free Thiol-Containing Peptide for Targeted Positron Emission Tomography Imaging of Fatty Acid Binding Protein 3 - UTU Research Portal

A1 Refereed original research article in a scientific journal

Switching the Chemoselectivity in the Preparation of [18F]FNA-N-CooP, a Free Thiol-Containing Peptide for Targeted Positron Emission Tomography Imaging of Fatty Acid Binding Protein 3

Authors: Dillemuth, Pyry; Lövdahl, Petter; Karskela, Tuomas; Ayo, Abiodun; Ponkamo, Jesse; Liljenbäck, Heidi; Paunonen, Sami; Kunnas, Jonne; Rajander, Johan; Tynninen, Olli; Rosenholm, Jessica M.; Roivainen, Anne; Laakkonen, Pirjo; Airaksinen, Anu J.; Li, Xiang-Guo

Publisher: American Chemical Society

Publication year: 2024

Journal: Molecular Pharmaceutics

Journal name in source: Molecular pharmaceutics

Journal acronym: Mol Pharm

Volume: 21

Issue: 8

First page : 4147

Last page: 4156

ISSN: 1543-8384

eISSN: 1543-8392

DOI: https://doi.org/10.1021/acs.molpharmaceut.4c00546

Web address : https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.4c00546

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/457242500

Abstract

Fatty acid binding protein 3 (FABP3) is expressed both in tumor cells and in the tumor vasculature, making it a potential target for medical imaging and therapy. In this study, we aimed to radiolabel a CooP peptide with a free amino and thiol group, and evaluate the radiolabeled product [¹⁸F]FNA-N-CooP for imaging FABP3 expression in breast cancer brain metastases by positron emission tomography. [¹⁸F]FNA-N-CooP was prepared by highly chemoselective N-acylation and characterized using different chemical approaches. We validated its binding to the target using in vitro tissue section autoradiography and performed stability tests in vitro and in vivo. [¹⁸F]FNA-N-CooP was successfully synthesized in 16.8% decay-corrected radiochemical yield with high radiochemical purity (98.5%). It exhibited heterogeneous binding on brain metastasis tissue sections from a patient with breast cancer, with foci of radioactivity binding corresponding to FABP3 positivity. Furthermore, the tracer binding was reduced by 55% in the presence of nonradioactive FNA-N-CooP a blocker, indicating specific tracer binding and that FABP3 is a viable target for [¹⁸F]FNA-N-CooP. Favorably, the tracer did not bind to necrotic tumor tissue. However, [¹⁸F]FNA-N-CooP displayed limited stability both in vitro in mouse plasma or human serum and in vivo in mouse, therefore further studies are needed to improve the stability [¹⁸F]FNA-N-CooP to be used for in vivo applications.

Funding information in the publication:
Research funded by Research Council of Finland (337530,350117,357910) | Turun Yliopistollinen Keskussairaala (11009)