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

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

Research output: Contribution to journalArticleScientificpeer-review

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.

Original languageEnglish
JournalMolecular Pharmaceutics
Volume21
Issue number8
Pages (from-to)4147-4156
Number of pages10
ISSN1543-8384
DOIs
Publication statusPublished - 2024
MoE publication typeA1 Journal article-refereed

Bibliographical note

Publisher Copyright:
© 2024 American Chemical Society.

Fields of Science

  • F-labeling
  • autoradiography
  • brain metastasis
  • CooP peptide
  • fatty acid binding protein 3
  • positron emission tomography
  • 317 Pharmacy

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