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Study of Binding Kinetics and Specificity of 99mTc-SSS-Complex and 99mTc-HMPAO to Blood Cells

机译:99mTc-SSS-Complex和99mTc-HMPAO与血细胞的结合动力学和特异性研究

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摘要

Nuclear medicine offers several techniques and procedures to image infection, but radiolabelled autologous white blood cells (WBCs) are still the gold standard. These cells are usually labelled with 111In or 99mTc bound to a hydrophobic chelating agent that allows these isotopes to pass through the plasma membrane and enter in the cytoplasm. The most common compound in Europe is HMPAO that efficiently chelates 99mTc. However, up to 20–40% of the complex is released from the cells in the first few hours. The aim of this study was to radiolabel a new compound, (S3CPh)2 (S2CPh)-complex (SSS-complex) with 99mTc and compare its binding kinetics and specificity for WBC with HMPAO. The SSS-complex was labelled with 99mTc and analysed by iTLC and RP-HPLC. In vitro quality controls included a stability assay in serum and saline. Results showed a labelling efficiency of 95 ± 1.2% and 98 ± 1.4% for 99mTc-SSS-complex and 99mTc-HMPAO, respectively (p=ns). 99mTc-SSS-complex was stable in serum and in saline up to 24 h (94 ± 0.1%). Cell labelling experiments showed a higher incorporation of 99mTc-SSS-complex than 99mTc-HMPAO by granulocytes (62.6 ± 17.8% vs 40.5 ± 15%, p=0.05), lymphocytes (59.9 ± 22.2% vs 29.4 ± 13.5%; p=0.03), and platelets (44.4 ± 24% vs 20.5 ± 10.7%; p=ns), but the release of radiopharmaceutical from granulocytes at 1 h was lower for HMPAO than for SSS-complex (10.3 ± 1.9% vs 21.3 ± 1.8%; p=0.001). In conclusion, 99mTc-SSS-complex, although showing high labelling efficiency, radiochemical purity, and stability, is not a valid alternative to 99mTc-HMPAO, for example, in vivo white blood cells labelling because of high lymphocyte and platelet uptake and rapid washout from granulocytes.
机译:核医学提供了几种对感染进行成像的技术和程序,但是放射性标记的自体白细胞(WBC)仍然是金标准。这些细胞通常用与疏水性螯合剂结合的 111 In或 99m Tc进行标记,疏水性螯合剂使这些同位素能够穿过质膜进入细胞质。欧洲最常见的化合物是HMPAO,可有效螯合 99m Tc。但是,在最初的几个小时内,高达20–40%的复合物会从细胞中释放出来。这项研究的目的是放射性标记具有 99m Tc的新化合物(S3CPh)2(S2CPh)-复合物(SSS-complex),并比较其与WMP和HMPAO的结合动力学和特异性。用 99m Tc标记SSS复合物,并通过iTLC和RP-HPLC分析。体外质量控制包括在血清和盐水中的稳定性测定。结果显示, 99m Tc-SSS-complex和 99m Tc-HMPAO的标记效率分别为95±1.2%和98±1.4%(p = ns)。 99m Tc-SSS-复合物在血清和盐水中稳定至24 h(94±0.1%)。细胞标记实验显示,粒细胞将 99m Tc-SSS-complex掺入的纤维比 99m Tc-HMPAO高(62.6±17.8%vs 40.5±15%,p = 0.05) ,淋巴细胞(59.9±22.2%vs 29.4±13.5%; p = 0.03)和血小板(44.4±24%vs 20.5±10.7%; p = ns),但对于HMPAO,在1ocyteh时粒细胞的放射性药物释放较低相比于SSS-complex(10.3±1.9%vs 21.3±1.8%; p = 0.001)。总之, 99m Tc-SSS-complex尽管显示出高标记效率,放射化学纯度和稳定性,但不是 99m Tc-HMPAO的有效替代品,例如,体内白细胞标记的原因是高淋巴细胞和血小板摄取以及粒细胞的快速清除。

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