METHOD OF PRODUCING A TECHNETIUM-99M COMPLEX WITH AN OCTREOTIDE DERIVATIVE FOR DIAGNOSING NEUROENDOCRINE TUMORS Russian patent published in 2019 - IPC C07K7/06 C07F13/00 A61K51/08 A61K103/10 A61K38/08 A61P35/00 

FIELD: chemistry; technological processes.

SUBSTANCE: invention relates to a method of producing a technetium-99m complex with an octreotide derivative for diagnosing neuroendocrine tumors, comprising mixing a phosphate-buffer solution of octreotide with pH 7.5–9.0 and a solution of acetonitrile containing 9-fluorenylmethyloxycarbonyl chloride (Fmoc-Cl), in molar ratio of 1:1–1.2, stirred for 15–60 minutes at temperature 20–60 °C. Mixture is purified by semi-preparative liquid chromatography. Fractions corresponding to Fmoc-(L-Lys)-octreotide are combined and lyophilized. Obtained Fmoc-(L-Lys)-octreotide is dissolved in dimethylformamide and succinimid-1-yl-6-(bis(pyridin-2-ylmethyl)amino)hexanoate is added in the presence of triethylamine for 6–10 hours while stirring, cleaning is carried out semi-preparatory liquid chromatography. Fractions corresponding to DPAH-(D-Phe)-Fmoc-(L-Lys)-octreotide are combined and lyophilized. Obtained DPAH-(D-Phe)-Fmoc-(L-Lys)-octreotide is hydrolyzed by dissolving it in a mixture of dimethylformamide and piperidine, and incubated for at least 30 min at room temperature, purifying by semi-preparative liquid chromatography and lyophilizing. To obtained DPAH-(D-Phe)-octreotide there added is solution of carbonyl technetium-99m with activity of technetium-99m 1 GBq, mixture is incubated at 40 °C for 60 minutes, solid-phase extraction is carried out, eluted with ethanol, diluted with sodium chloride solution.

EFFECT: high output of DPAH-modified octreotide, high radiochemical purity of the technetium-99m complex with DPAH-modified octreotide.

1 cl, 6 dwg, 15 ex