Preparation and biological evaluation of [(99m)Tc/EDDA/Tricine/HYNIC(0), BzThi(3)]-octreotide for somatostatin receptor-positive tumor imaging.

Somatostatin-derived analogues play an important role in the diagnosis and treatment of neuroendocrine tumors. The aim of this study was to evaluate a new somatostatin analogue designed for labeling with (99m)Tc: [6-hydrazinopyridine-3-carboxylic acid (HYNIC(0)), β-(3-benzothienyl)-Ala (BzThi(3))]-octreotide ([HYNIC]-BOC), using ethylenediamine-N,N'-diacetic acid (EDDA) and tricine as coligands. Synthesis was performed on a solid phase using a standard Fmoc strategy. The HYNIC-peptide conjugate was radiolabeled with (99m)Tc and characterized by ITLC and high-performance liquid chromatography (HPLC). In vitro studies were carried out in sstr2 expressing AR4-2J cell lines. In vivo distribution studies were performed in rats bearing the AR4-2J tumor. The radiolabeled complex could be prepared at high-specific activities and >95% radiochemical yield as determined by HPLC. The peptide conjugate showed high-affinity binding for sstr2. The radioligand showed high and specific internalization into AR4-2J cells (18.19%±0.21% at 4 hours). In vivo distribution studies in rats bearing tumor have shown a receptor-specific uptake of radioactivity in somatostatin receptor-positive organs. After 4 hours, uptake in the AR4-2J tumor was 1.71%±0.36% injected dose per gram tissue (%ID/g). These data show that [(99m)Tc/EDDA/Tricine/HYNIC(0), BzThi(3)]-octreotide is a specific radioligand for the somatostatin receptor-positive tumors and is a suitable candidate for clinical studies.