Development of a method for preparing octreotide derivative for diagnosis of neuroendocrine tumors

• Published in: Bi͡u︡lletenʹ Sibirskoĭ medit͡s︡iny Vol. 18; no. 3; pp. 72 - 80
• Main Authors: Larkina, M. S., Podrezova, E. V., Bragina, O. D., Tagirova, E. A., Chernov, V. I., Yusubov, M. S., Nesterov, E. A., Skuridin, V. S., Krivoshchekov, S. V., Yanovskaya, E. A., Gurto, R. V., Belousov, M. V.
• Format: Journal Article
• Language: English
• Published: Siberian State Medical University (Tomsk) 27-10-2019
• Subjects: нейроэндокринные опухоли; октреотид; офэкт; соматостатиновые рецепторы; технеций-99м; хелатирующий агент
• ISSN: 1682-0363; 1819-3684
• DOI: 10.20538/1682-0363-2019-3-72-80

Currently the development of technologies for labeling somatostatin with technetium-99m for diagnosing radionuclide neuroendocrine tumors is under way. Somatostatin analogues are binded with technetium99m only by the preliminary addition of a chelating agent. Therefore, it is important to develop a method for preparation of an octreotide derivative by modifying octreotide with precursors: ligands with high chelating ability for its tight binding with technetium-99m. ω-Bis(pyridin-2-ylmethyl)amino)aliphatic acids can be used successfully as such precursors.
The purpose of the study
was to develop a method for obtaining a new octreotide derivative for diagnosing neuroendocrine tumors.
Materials and methods
. The somatostatin octreotide analogue was used as the object of the study; succinimid-1-yl 6-(bis(pyridin-2-ylmethyl)amino)hexanoate was used as a chelating agent. Methods of high performance liquid chromatography and mass spectrometry were used to separate and analyze the synthesized compounds.
Results
. A method to produce an original octreotide derivative using a succinimid-1-yl 6-(bis(pyridin2-ylmethyl)amino)hexanoate as a chelating agent was proposed. The conditions of analytical and semipreparative HPLC for the analysis and purification of the active octreotide derivative (a monosubstituted derivative of the amino acid residue of D-phenylalanine) were suggested.
Conclusion
. The synthesized derivative of octreotide has a chelating center for strong binding to technetium-99m in its structure, which can be useful for diagnosing neuroendocrine tumors.