Preparation and preliminary biological evaluation of Gluc-Lys([Al18F]NOTA)-KE108

Abstract

BackgroundRadionuclide labeled somatostatin analogs can specifically bind to somatostatin receptors (SSTRs) on the cell surface of neuroendocrine tumors (NETs), hence be used for imaging or treatment of NETs.PurposeThis study aims to label glycosylated KE108 protein with 18F nuclide, and to investigate the distributions and PET imaging of this probe in mice in vivo.MethodsA novel 18F-radiolabeled somatostatin analogue probe Gluc-Lys([Al18F]NOTA)-KE108 was designed and synthesized, which linked 18F nuclide and glycosylated KE108 protein by coupling bifunctional chelator (NOTA) to target SSTR positive tumors. The in vitro physicochemical properties, in vitro cell binding, ex vivo biodistribution and in vivo imaging of Gluc-Lys([Al18F]NOTA)-KE108 were further investigated to evaluate the SSTR targeting ability and feasibility of PET imaging in the diagnosis of NETs.ResultsThe efficiency of Gluc-Lys([Al18F]NOTA)-KE108 obtained with moderate labelling is (30±5)% without corrected (n=6), and the radiochemical purity is higher than >95%. The radiochemical yield is ((20±5)%, uncorrected) (n=6), and the total synthesis time is about 20 min. The specific activity is more than 1.37 GBq∙μmol-1. The probe shows expected nanomolar binding affinity in SSTR-positive AR42J and BON1 tumor cells, which Kd values are (152.3±49.1) nmol∙L-1 and (45.5±13.6) nmol∙L-1, respectively, and can be specifically inhibited, showing high SSTR targeting ability. In PET imaging of AR42J tumor bearing mice, Gluc-Lys([Al18F]NOTA)-KE108 has a high uptake of radioactivity and a high ratio of tumor to muscle uptake.ConclusionsGluc-Lys([Al18F]NOTA)-KE108 has high hydrophilicity and good stability in vitro, hence be served as a potential imaging agent for SSTR-positive tumors.

Keywords

• somatostatin receptor (sstr)
• complex aluminum fluoride
• neuroendocrine tumors (nets)
• ke108 peptides