Switching the Chemoselectivity in the Preparation of [ 18 F]FNA- N -CooP, a Free Thiol-Containing Peptide for Targeted Positron Emission Tomography Imaging of Fatty Acid Binding Protein 3.
Pyry DillemuthPetter LövdahlTuomas KarskelaAbiodun AyoJesse PonkamoHeidi LiljenbäckSami PaunonenJonne KunnasJohan RajanderOlli TynninenJessica M RosenholmAnne RoivainenPirjo LaakkonenAnu J AiraksinenXiang-Guo LiPublished in: Molecular pharmaceutics (2024)
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 [ 18 F]FNA- N -CooP for imaging FABP3 expression in breast cancer brain metastases by positron emission tomography. [ 18 F]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. [ 18 F]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 [ 18 F]FNA- N -CooP. Favorably, the tracer did not bind to necrotic tumor tissue. However, [ 18 F]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 [ 18 F]FNA- N -CooP to be used for in vivo applications.
Keyphrases
- binding protein
- positron emission tomography
- fine needle aspiration
- computed tomography
- pet imaging
- fatty acid
- high resolution
- ultrasound guided
- pet ct
- brain metastases
- healthcare
- poor prognosis
- case report
- young adults
- white matter
- fluorescence imaging
- resting state
- mass spectrometry
- climate change
- risk assessment
- functional connectivity
- human health
- molecularly imprinted
- subarachnoid hemorrhage
- tandem mass spectrometry