Department of Pharmacy & Pharmacology, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, the Netherlands.
Department of Nuclear Medicine, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, the Netherlands.
J Chromatogr B Analyt Technol Biomed Life Sci. 2021 May 1;1171:122605. doi: 10.1016/j.jchromb.2021.122605. Epub 2021 Feb 27.
Lutetium-177 [Lu] tetra-azacyclododecanetetra-acetic acid [DOTA]-(Tyr3)-octreotate [TATE] ([Lu]Lu-DOTA-TATE) is a radiopeptide used for peptide receptor radionuclide therapy in patients with neuroendocrine tumours (NETs). This radiopeptide is made by labelling the ligand octreotate with Lutetium-177 using the linker DOTA. After labelling, and before clinical application quality control of the radiopeptide is needed and the radiochemical purity is assessed. Acceptance limits for radiochemical purity should be within 90-110% of the label claim for radiopharmaceuticals for diagnostic use and within 95-105% of the label claim for radiopharmaceuticals for therapeutic use. Moreover, the amount of unlabelled [Lu]LuCl cannot exceed 2% of the radioactive dose. Since no monograph is available for [Lu]Lu-DOTA-TATE in the European Pharmacopeia (Ph Eur), this article describes the development and validation of a high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection and radiodetection. A Waters Acquity Arc UHPLC system equipped with a Waters 2998 photodiode array (PDA) detector was used coupled to a Berthold Lb 514 Flowstar detector equipped with a BGO-X gamma measuring cell. A reversed phase Symmetry Shield C18 column (4.6 mm × 250 mm, 5 µm) was used for chromatographic separation. A flow of 1.5 mL/min was maintained during analysis, using 0.1% TFA in water as mobile phase A and 0.1% TFA in ACN as mobile phase B. The retention time was around 1.7 min and 13.5 min for [Lu]LuCl and [Lu]Lu-HA-DOTA-TATE, respectively. Stock solutions of [Lu]LuCl were made by serial dilution and were injected to test for linearity, accuracy and precision, carry over and signal-to-noise ratio. A [Lu]Lu-HA-DOTA-TATE sample was prepared and injected to determine the carry over. The results showed that the method is linear over a range of 0.300-130 MBq/mL, which covers the range for clinical samples, provided that the clinical sample is diluted ten times before analysis. The LLOQ can be measured accurately even after dilution, with a signal-to-noise ratio of at least 5. In short, the method is accurate, precise and sensitive and can be implemented as part of the quality control of [Lu]Lu-HA-DOTA-TATE.
镥-177[Lu]四氮杂环十二烷四乙酸[DOTA]-(Tyr3)-奥曲肽[TATE]（[Lu]Lu-DOTA-TATE）是一种放射性肽，用于神经内分泌肿瘤（NETs）患者的肽受体放射性核素治疗。这种放射性肽是通过用配体奥曲肽标记镥-177，然后使用连接体 DOTA 制成的。标记后，在临床应用之前，需要对放射性肽进行质量控制，并评估放射化学纯度。用于诊断用途的放射性药物的放射化学纯度接受限值应为标签声称值的 90-110%，用于治疗用途的放射性药物的放射化学纯度接受限值应为标签声称值的 95-105%。此外，未标记的[Lu]LuCl 的量不得超过放射性剂量的 2%。由于欧洲药典（Ph Eur）中没有[Lu]Lu-DOTA-TATE 的专论，因此本文描述了一种使用带有紫外（UV）检测和放射检测的高效液相色谱（HPLC）方法的开发和验证。使用配备 Waters 2998 光电二极管阵列（PDA）检测器的 Waters Acquity Arc UHPLC 系统，与配备 BGO-X 伽马测量池的 Berthold Lb 514 Flowstar 检测器耦合。使用反相 Symmetry Shield C18 柱（4.6mm×250mm，5μm）进行色谱分离。在分析过程中保持 1.5mL/min 的流速，使用水作为流动相 A 的 0.1%TFA 和作为流动相 B 的 ACN 中的 0.1%TFA。[Lu]LuCl 和[Lu]Lu-HA-DOTA-TATE 的保留时间分别约为 1.7 分钟和 13.5 分钟。通过连续稀释制备[Lu]LuCl 储备溶液，并进行线性、准确性和精密度、携带和信噪比测试。制备[Lu]Lu-HA-DOTA-TATE 样品并进行进样以确定携带。结果表明，该方法在 0.300-130MBq/mL 的范围内呈线性，这涵盖了临床样本的范围，前提是临床样本在分析前稀释十倍。即使在稀释后，LLOQ 也可以准确测量，信噪比至少为 5。简而言之，该方法准确、精密且灵敏，可作为[Lu]Lu-HA-DOTA-TATE 质量控制的一部分实施。
