Synthesis and Optimization of the Labeling Procedure of 99mTc-Hynic-Interleukin-2 for In vivo Imaging of Activated T lymphocytes
Synthesis and Optimization of the Labeling Procedure of 99mTc-Hynic-Interleukin-2 for In vivo Imaging of Activated T lymphocytes
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DOI：
10.1007/s11307-009-0285-1
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发表时间：
2010-10-01
影响因子：
3.1
通讯作者：
Signore, Alberto
中科院分区：
文献类型：
--
作者：
D'Alessandria, Calogero;di Gialleonardo, Valentina;Signore, Alberto
我们以前描述了用I-123和Tc-99 m-N3 S标记白细胞介素-2（IL-2）。这两种放射性药物已成功应用于人体，对几种炎性病变和自身免疫性疾病进行成像，其特征在于表达IL 2受体（CD 25）的组织浸润淋巴细胞。然而，这两种放射性药物都有一些特定的缺点，如成本和合成时间。在这里，我们描述了一种新的改进的方法标记的白细胞介素-2与Tc-99 m使用HYNIC-NHS和tricine作为共配体。对试剂浓度和标记条件进行了几次优化，以使程序标准化。标记后，IL 2纯化的TC 2反相色谱和测试在体外和体内，在小鼠和正常志愿者。结果表明，这种标记方法是廉价的，快速的，可靠的，和可重复的，导致产品具有高比活性（153 A μ Ci/A μ g），高稳定性和能够在体外结合到CD 25阳性细胞。在小鼠和人志愿者体内的生物分布与Tc-99 m-N3 S-IL 2没有显示任何显著差异。总之，优化的Tc-99 m-HYNIC-IL 2在生产成本和时间方面具有很大的优势，并且可以考虑将简单的试剂盒制剂常规应用于受自身免疫性疾病、移植排斥或其他慢性炎症性疾病影响的患者的研究。
We have previously described the labeling of interleukin-2 (IL2) with I-123 and Tc-99m-N3S. Both radiopharmaceuticals were successfully applied in humans to image several inflammatory lesions and autoimmune diseases characterized by tissue infiltrating lymphocytes expressing the IL2 receptor (CD25). However, both radiopharmaceuticals had some specific disadvantages, such as cost and time of synthesis.Here, we describe a new improved method for labeling interleukin-2 with Tc-99m using HYNIC-NHS and tricine as coligand. Several optimizations of reagent concentrations and labeling conditions were performed in order to standardize the procedure. After labeling, IL2 was purified by tC2 reverse-phase chromatography and tested in vitro and in vivo, in mice and in a normal volunteer. Results showed that this labeling procedure is cheap, fast, reliable, and reproducible, leading to a product with high specific activity (153 A mu Ci/A mu g), high stability and capable of binding in vitro to CD25 positive cells. In vivo biodistribution in mice and human volunteer did not show any significant different from Tc-99m-N3S-IL2.In conclusion, the optimization of Tc-99m-HYNIC-IL2 has a great advantage in terms of cost and time of production and a simple kit formulation can be considered for routine application to study patients affected by autoimmune diseases, graft rejection, or other chronic inflammatory disorders.