From octreotide to shorter analogues: Synthesis, radiolabeling, stability

Autor:	Nikolay Titchenko, B. V. Egorova, D. S. Khachatryan, Natalya Podkhalyuzina, Dmitry Avdeev, Stepan N. Kalmykov, Ekaterina V. Matazova, Anzhelika Yakusheva, Vasily Nikolaevich Osipov, G.A. Posypanova
Rok vydání:	2019
Předmět:	Conjugated system Octreotide Mass spectrometry 01 natural sciences Biochemistry High-performance liquid chromatography Pentapeptide repeat 030218 nuclear medicine & medical imaging Analytical Chemistry Heterocyclic Compounds 1-Ring 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Stability Drug Discovery Animals DOTA Radiology Nuclear Medicine and imaging Chelation Amino Acid Sequence neoplasms Spectroscopy Radiochemistry Tetrapeptide 010405 organic chemistry Chemistry Organic Chemistry 0104 chemical sciences Isotope Labeling Positron-Emission Tomography Radiopharmaceuticals Conjugate Nuclear chemistry
Zdroj:	Journal of Labelled Compounds and Radiopharmaceuticals. 62:718-728
ISSN:	0362-4803
DOI:	10.1002/jlcr.3799
Popis:	This study aims at analyzing complexation properties of two new short somatostatin analogues, their synthesis, radiolabeling with 44 Sc, 207 Bi, and 152 Eu and stability in vitro. Short tetrapeptide Phe-d-Trp-Lys-Thr and pentapeptide Thz-Phe-d-Trp-Lys-Thr were first conjugated with the DOTA macrocyclic chelator. These conjugates were radiolabeled with 44 Sc, 207 Bi, and 152 Eu and characterized by thin-layer chromatography (TLC) and HPLC. The radiochemical purity was measured using digital autoradiography and gamma spectrometry. Optimum conditions of DOTA-conjugate labeling were found: 0.1mM, pH 8.0 to 8.4 at 90°C for DOTA-tetrapeptide complexes with 207 Bi and 152 Eu; 0.05mM, pH 4.0 to 5.0 at 90°C for 44 Sc-DOTA-tetrapeptide; 0.2mM, pH 4.0 to 5.0 at 90°C for 44 Sc-DOTA-pentapeptide. Complexes of DOTA-pentapeptide with 207 Bi and 152 Eu of radiochemical purity more than 95% were probably unstable at temperature higher than 37°C and were obtained at 37°C, pH 8.0 to 8.4 within 4 days. Mass spectra of the Eu-DOTA-pentapeptide revealed the presence of small fragments of the pentapeptide conjugate in the complex solution. in vitro stability studies were performed in saline in the presence of serum proteins and biologically relevant metal cations. All complexes demonstrated no cation release in vitro within 1 to 4 hours.
Databáze:	OpenAIRE
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