Synthesis and preliminary in vivo studies of radiopharmaceuticals based on metallocomplexes of technetium-99m radionuclide with somatostatin analogues

Neuroendocrine tumors are heterogeneous group of malignant neoplasms, originating from neuro-endocrine cells. Their key feature is the overexpression of somatostatin receptors, which can serve as molecular targets and provide the possibility of radiopharmaceuticals (RPs) targeting. The use of synthetic peptide-based somatostatin analogues RPs, labelled with technetium-99m (99mTc), allows to determine the localization of the primary tumor focus and metastasis, and also to monitor the response of treatment with subsequent observation of disease recurrence. The aim of this study was to synthesize 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE metal complexes and to evaluate their biodistribution in vivo. The metal complexes 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE were synthesized using EDDA and tricine as co-ligands with heating to 95 oC and adding of tin chloride SnCl2·2H2O. The radiochemical purity of 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE was higher than 90%. A single intravenous injection of metal complexes in mice with transplanted SK-Mel-28 xenografts demonstrated increased accumulation of both RPs in tumor as compared with majority of organs and tissues, except kidneys. The uptake of 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE in kidneys were 1.366-49.637 %/g and 4.797-46.661 %/g, respectively. No statistically significant differences in 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE accumulation in organs and tissues were observed. The obtained results demonstrate the possibility of further RPs application for neuroendocrine tumors imaging.