A novel Buthus martensiiKarsch chlorotoxin derivative for glioma SPECT imaging
A novel Buthus martensiiKarsch chlorotoxin derivative for glioma SPECT imaging
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一种用于神经胶质瘤 SPECT 成像的新型马氏螳螂卡氏氯毒素衍生物
DOI：
10.1039/d0nj03302b
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发表时间：
2020
影响因子：
3.3
通讯作者：
Zhao Jinhua
中科院分区：
文献类型：
--
作者：
Zhao Lingzhou;Zhu Jingyi;Wang Tiantian;Liu Changcun;Song Ningning;Wu Shan;Qiao Wenli;Yang Jiqin;Zhu Meilin;Zhao Jinhua
越来越多的研究表明，蝎子毒液和毒素在癌症中的诊断和治疗潜力，包括代表最致命的原发性脑肿瘤的恶性胶质瘤。蝎毒氯毒素（Chlorotoxin，CTX）和蝎毒氯毒素样肽（Buthus martensii Karsch chlorotoxin，BmK CT）是一种特异性胶质瘤显像剂和治疗剂。本研究根据天然CTX和BmK CT的氨基酸序列设计并制备了一种新的BmK CT衍生物（BmK CT-D），并探讨了99 mTc标记的BmK CT-D作为单正电子发射计算机断层扫描（SPECT）显像剂用于胶质瘤诊断的可能性。结果表明，BmK CT-D肽具有较好的细胞相容性，与BmK CT相比，其细胞摄取明显提高，且能被99 mTc-三羰基化学标记，放化产率高，体外稳定性好。此外，所形成的99 mTc-BmK CT-D能够用作体外胶质瘤细胞和荷瘤小鼠体内SPECT成像的探针，表明所设计的肽是一种有前途的肿瘤成像靶向剂。
An increasing number of studies show the diagnostic and therapeutic potential of scorpion venoms and toxins in cancer, including malignant glioma that represents the most fatal primary brain tumors. Chlorotoxin (CTX) and a CTX-like peptide Buthus martensii Karsch chlorotoxin (BmK CT) derived from scorpion venoms, have been identified as glioma-specific agents for imaging and therapy. In this study, we designed and manufactured a new BmK CT derivative (BmK CT-D) according to the amino acid sequences of native CTX and BmK CT and investigated the possibility of 99mTc-labeled BmK CT-D as a single-positron emission computed tomography (SPECT) imaging agent for glioma diagnosis. The data indicated that the BmK CT-D peptide had good cytocompatibility, improved cellular uptake compared to BmK CT, and could be readily radiolabeled by 99mTc via99mTc-tricarbonyl chemistry with high radiochemical yield and stability in vitro. Moreover, the formed 99mTc-BmK CT-D was able to be used as a probe for SPECT imaging of glioma cells in vitro and in tumor-bearing mice in vivo, indicating that the designed peptide is a promising targeting agent for tumor imaging.