Chlorotoxin-Conjugated Multifunctional Dendrimers Labeled with Radionuclide 131I for Single Photon Emission Computed Tomography Imaging and Radiotherapy of Gliomas.
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'-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 (0-20 μM) 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.
Department of Nuclear Medicine, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University , Shanghai 200080, People's Republic of China.
Lingzhou
L
Zhao
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University , Shanghai 201620, People's Republic of China.
Jingyi
J
Zhu
Department of Nuclear Medicine, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University , Shanghai 200080, People's Republic of China.
Yongjun
Y
Cheng
College of Chemistry, Chemical Engineering and Biotechnology, Donghua University , Shanghai 201620, People's Republic of China.
Zhijuan
Z
Xiong
Experiment Center, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University , Shanghai 200080, People's Republic of China.
Yueqin
Y
Tang
Department of Nuclear Medicine, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University , Shanghai 200080, People's Republic of China.
Lilei
L
Guo
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University , Shanghai 201620, People's Republic of China.|College of Chemistry, Chemical Engineering and Biotechnology, Donghua University , Shanghai 201620, People's Republic of China.
Xiangyang
X
Shi
Department of Nuclear Medicine, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University , Shanghai 200080, People's Republic of China.
Jinhua
J
Zhao
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry* / Q000633:toxicity; D005260:Female; D005910:Glioma / Q000175:diagnosis* / Q000401:mortality / Q000532:radiotherapy; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D011092:Polyethylene Glycols / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D012604:Scorpion Venoms / Q000737:chemistry* / Q000633:toxicity; D015996:Survival Rate; D015899:Tomography, Emission-Computed, Single-Photon
D050091:Dendrimers; D007457:Iodine Radioisotopes; C104700:PAMAM Starburst; D019275:Radiopharmaceuticals; D012604:Scorpion Venoms; C091539:Chlorotoxin; D011092:Polyethylene Glycols; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
SPECT imaging; chlorotoxin; dendrimers; glioma; radiotherapy