Chlorotoxin-Conjugated Multifunctional Dendrimers Labeled with Radionuclide 131I for Single Photon Emission Computed Tomography Imaging and Radiotherapy of Gliomas

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• 作者：Lingzhou Zhao ; Jingyi Zhu ; Yongjun Cheng ; Zhijuan Xiong ; Yueqin Tang ; Lilei Guo ; Xiangyang Shi ; Jinhua Zhao
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2015
• 出版时间：September 9, 2015
• 年：2015
• 卷：7
• 期：35
• 页码：19798-19808
• 全文大小：636K
• ISSN：1944-8252

文摘

Chlorotoxin-conjugated multifunctional dendrimers labeled with radionuclide ¹³¹I were synthesized and utilized for targeted single photon emission computed tomography (SPECT) imaging and radiotherapy of cancer. In this study, generation five amine-terminated poly(amidoamine) dendrimers were used as a platform to be sequentially conjugated with polyethylene glycol (PEG), targeting agent chlorotoxin (CTX), and 3-(4鈥?hydroxyphenyl)propionic acid-OSu (HPAO). This was followed by acetylation of the remaining dendrimer terminal amines and radiolabeling with ¹³¹I to form the targeted theranostic dendrimeric nanoplatform. We show that the dendrimer platform possessing approximately 7.7 CTX and 21.1 HPAO moieties on each dendrimer displays excellent cytocompatibility in a given concentration range (0鈥?0 渭M) and can specifically target cancer cells overexpressing matrix metallopeptidase 2 (MMP2) due to the attached CTX. With the attached HPAO moiety having the phenol group, the dendrimer platform can be effectively labeled with radioactive ¹³¹I with good stability and high radiochemical purity. Importantly, the ¹³¹I labeling renders the dendrimer platform with an ability to be used for targeted SPECT imaging and radiotherapy of an MMP2-overexpressing glioma model in vivo. The developed radiolabeled multifunctional dendrimeric nanoplatform may hold great promise to be used for targeted theranostics of human gliomas.