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 language | English |
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Journal | Molecular Pharmaceutics |
Volume | 21 |
Issue number | 8 |
Pages (from-to) | 4147-4156 |
Number of pages | 10 |
ISSN | 1543-8384 |
DOIs | |
Publication status | Published - 2024 |
MoE publication type | A1 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