Initial evaluation of 99m Tc‐labeled anti‐carcinoembryonic antigen single‐chain fragment variable for micro‐single‐photon emission computed tomography imaging in mice with colorectal cancer
Initial evaluation of 99m Tc‐labeled anti‐carcinoembryonic antigen single‐chain fragment variable for micro‐single‐photon emission computed tomography imaging in mice with colorectal cancer
复制标题
99m Tc标记抗癌胚抗原单链片段变量对结直肠癌小鼠微单光子发射计算机断层扫描成像的初步评价
DOI：
10.1002/jlcr.3960
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发表时间：
2022
影响因子：
1.8
通讯作者：
Zhi Yang
中科院分区：
文献类型：
--
作者：
Xue Qin;Xiangxi Meng;Yao Xiong;Xiaoyi Guo;Yanan Ren;Li Wen;Qian Zhang;Hua Zhu;Zhi Yang
癌胚抗原（CEA）已成为多种肿瘤疾病的重要分子靶点，包括CEA过表达的结直肠癌。在这项研究中，我们报道了一种新的抗CEA单链片段变量（scFv‐96NRT，最大效果的50%浓度为46 ng/ml）的产生和放射性标记，并评估了[99mTc]Tc‐scFv‐96NRT在CEA表达的无创检测中的作用。[99mTc]Tc - scFv - 96NRT采用一步还原法合成，标记率为>95%，放射化学纯度为>98%，摩尔活性为10-11 GBq/μmol。[99mTc]Tc‐scFv‐96NRT在0.01 M磷酸盐缓冲盐水（PBS）和5%人血清白蛋白（HSA）中表现出很高的稳定性。它在CEA过表达细胞中表现出高摄取。BALB/c小鼠的生物分布研究表明，该探针可迅速从血液中清除，并在肾脏中观察到最高的滞留。[99mTc]Tc - scFv - 96NRT的微单光子发射计算机断层扫描（micro - SPECT）成像显示出特定的积累模式，因为过量scFv - 96NRT阻断实验抑制了肿瘤的摄取。这些初步结果表明，[99mTc]Tc‐scFv‐96NRT是一种潜在的非侵入性分子探针，用于CEA过表达肿瘤的成像。
Carcinoembryonic antigen (CEA) has emerged as an important molecular target for several neoplastic diseases, including colorectal cancer with CEA over‐expression. In this study, we report the production and radiolabeling of a novel anti‐CEA single‐chain fragment variable (scFv‐96NRT, concentration for 50% of maximal effect 46 ng/ml), and evaluation of [99mTc]Tc‐scFv‐96NRT in non‐invasive detection of CEA expression. [99mTc]Tc‐scFv‐96NRT was synthesized by one step reduction in labeling yield of >95% with radiochemical purity of >98% and molar activity of 10–11 GBq/μmol. [99mTc]Tc‐scFv‐96NRT showed high stability in 0.01 M phosphate‐buffered saline (PBS) and 5% human serum albumin (HSA). It exhibited elevated uptake in CEA over‐expressing cells. Biodistribution studies in BALB/c mice revealed that the probe was cleared from blood rapidly, and the highest retention was observed in the kidneys. The micro‐single‐photon emission computed tomography (micro‐SPECT) imaging of [99mTc]Tc‐scFv‐96NRT showed a specific accumulation pattern, as blocking experiment with excess scFv‐96NRT suppressed the tumor uptake. These preliminary results suggest that [99mTc]Tc‐scFv‐96NRT is a potential non‐invasive molecular probe for imaging tumors with CEA over‐expression.