دورية
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
| العنوان: | 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 |
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| المؤلفون: | 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 |
| المصدر: | Molecular Pharmaceutics; 20240101, Issue: Preprints |
| مستخلص: | 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. |
| قاعدة البيانات: | Supplemental Index |
Find this issue from the American Chemical Society | تدمد: | 15438384 15438392 |
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| DOI: | 10.1021/acs.molpharmaceut.4c00546 |