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 TLC and HPLC. The radiochemical purity was measured using digital autoradiography and gamma-spectrometry. Optimum conditions of DOTA-conjugate labeling were found: 0.1 mM, pH 8.0-8.4 at 90°C for DOTA-tetrapeptide complexes with 207 Bi and 152 Eu; 0.05 mM, pH 4.0-5.0 at 90°C for 44 Sc-DOTA-tetrapeptide; 0.2 mM, pH 4.0-5.0 at 90°C for 44 Sc-DOTA-pentapeptide. Complexes of DOTA-pentapeptide with 207 Bi and 152 Eu of radiochemical purity ˃ 95% were probably unstable at temperature higher than 37°C and were obtained at 37°C, pH 8.0-8.4 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 1-4 hours.

中文翻译：

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从奥曲肽到更短的类似物：合成、放射性标记、稳定性

本研究旨在分析两种新的短促生长抑素类似物的络合特性、它们的合成、44 Sc、207 Bi 和 152 Eu 的放射性标记以及体外稳定性。短四肽 Phe-D-Trp-Lys-Thr 和五肽 Thz-Phe-D-Trp-Lys-Thr 首先与 DOTA 大环螯合剂结合。这些缀合物用 44 Sc、207 Bi 和 152 Eu 进行放射性标记，并通过 TLC 和 HPLC 进行表征。放射化学纯度使用数字放射自显影和伽马光谱法测量。发现 DOTA 偶联物标记的最佳条件：0.1 mM，pH 8.0-8.4，90°C 下，含有 207 Bi 和 152 Eu 的 DOTA-四肽复合物；对于 44 Sc-DOTA-四肽，0.05 mM，pH 4.0-5.0，90°C；对于 44 Sc-DOTA-五肽，0.2 mM，pH 4.0-5.0，90°C。DOTA-五肽与 207 Bi 和 152 Eu 的放射化学纯度 ˃ 95% 的复合物可能在高于 37°C 的温度下不稳定，并在 37°C、pH 8.0-8.4 下在 4 天内获得。Eu-DOTA-五肽的质谱显示在复合溶液中存在五肽缀合物的小片段。在存在血清蛋白和生物学相关金属阳离子的情况下，在盐水中进行体外稳定性研究。所有复合物在体外 1-4 小时内均未显示出阳离子释放。在存在血清蛋白和生物学相关金属阳离子的情况下，在盐水中进行体外稳定性研究。所有复合物在体外 1-4 小时内均未显示出阳离子释放。在存在血清蛋白和生物学相关金属阳离子的情况下，在盐水中进行体外稳定性研究。所有复合物在体外 1-4 小时内均未显示出阳离子释放。