title: Radionuclide (131)I-labeled multifunctional dendrimers for targeted SPECT imaging and radiotherapy of tumors.
abstract: We report the synthesis, characterization, and utilization of radioactive (131)I-labeled multifunctional dendrimers for targeted single-photon emission computed tomography (SPECT) imaging and radiotherapy of tumors. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5·NH2) were sequentially modified with 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO) and folic acid (FA) linked with polyethylene glycol (PEG), followed by acetylation modification of the dendrimer remaining surface amines and labeling of radioactive iodine-131 ((131)I). The generated multifunctional (131)I-G5·NHAc-HPAO-PEG-FA dendrimers were characterized via different methods. We show that prior to (131)I labeling, the G5·NHAc-HPAO-PEG-FA dendrimers conjugated with approximately 9.4 HPAO moieties per dendrimer are noncytotoxic at a concentration up to 20 μM and are able to target cancer cells overexpressing FA receptors (FAR), thanks to the modified FA ligands. In the presence of a phenol group, radioactive (131)I is able to be efficiently labeled onto the dendrimer platform with good stability and high radiochemical purity, and render the platform with an ability for targeted SPECT imaging and radiotherapy of an FAR-overexpressing xenografted tumor model in vivo. The designed strategy to use the facile dendrimer nanotechnology may be extended to develop various radioactive theranostic nanoplatforms for targeted SPECT imaging and radiotherapy of different types of cancer.
authors.affiliation: 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.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Nuclear Medicine, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, People's Republic of China. zhaojinhua1963@126.com.
authors.forename: Lingzhou
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Nuclear Medicine, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, People's Republic of China. zhaojinhua1963@126.com.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China. xshi@dhu.edu.cn.
authors.forename: Zhijuan
authors.initials: Z
authors.lastname: Xiong
authors.affiliation: Experiment Center, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, People's Republic of China.
authors.forename: Yueqin
authors.initials: Y
authors.lastname: Tang
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China. xshi@dhu.edu.cn.
authors.forename: Mingwu
authors.initials: M
authors.lastname: Shen
authors.affiliation: Department of Nuclear Medicine, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, People's Republic of China. zhaojinhua1963@126.com.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Zhao
authors.affiliation: 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 and College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China. xshi@dhu.edu.cn.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Shi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005492:Folic Acid / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000532:radiotherapy; D011073:Polyamines / Q000737:chemistry / Q000494:pharmacology; D011859:Radiography; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: D050091:Dendrimers; D007457:Iodine Radioisotopes; C531249:Poly(amidoamine); D011073:Polyamines; D005492:Folic Acid