title: A Novel Copolymer-Based Functional SPECT/MR Imaging Agent for Asialoglycoprotein Receptor Targeting.
abstract: The aim of this study is to develop a copolymer-based single-photon emission computed tomography/magnetic resonance (SPECT/MR) dual-modality imaging agent that can be labeled with both technetium-99m (99mTc) and gadolinium (Gd) and target asialoglycoprotein receptor (ASGPR) via galactose. Monomers of N-p-vinylbenzyl-6-(2-(4-dimethylamino)benzaldehydehydrazono) nicotinate (VNI) for labeling of99mTc, 5,8-bis(carboxymethyl)-3-oxo-11-(2-oxo-2-((4-vinylbenzyl)amino)ethyl)-1-(4-vinylphenzyl)-2,5,8,11-tetraazatridecan-13-oic acid (V2DTPA) for labeling of Gd, and vinylbenzyl-O-β-d-galactopyranosyl-d-gluconamide (VLA) for targeting ASGPR were synthesized, respectively. Then the copolymer P(VLA-co-VNI-co-V2DTPA) (pVLND2) was synthesized and characterized by gel permeation chromatography, dynamic light scattering, and high-performance liquid chromatography analysis. After labeling with99mTc and Gd simultaneously, the radiochemical purity, toxicity, relaxivity (r1), and in vivo SPECT/MR imaging in mice were evaluated. Single-photon emission computed tomography/magnetic resonance imaging and biodistribution results showed that pVLND2could target ASGPR well. The significantly improved signal to noise ratio was observed in mice liver during MR imaging. All the results suggest that this novel kind of copolymer has the potential to be further developed as a functional SPECT/MR imaging agent.
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.|Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Zhide
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Deliang
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, China.
authors.forename: Guibing
authors.initials: G
authors.lastname: Chen
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Rongqiang
authors.initials: R
authors.lastname: Zhuang
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Manli
authors.initials: M
authors.lastname: Song
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wu
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China zhangxzh@xmu.edu.cn.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000378:metabolism*; D002251:Carbon Tetrachloride / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000000981:diagnostic imaging* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005682:Gadolinium / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D051379:Mice; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000737:chemistry*; D059629:Signal-To-Noise Ratio; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D037263:Asialoglycoprotein Receptor; D011108:Polymers; D019275:Radiopharmaceuticals; D013667:Technetium; D005682:Gadolinium; D002251:Carbon Tetrachloride
keywords: SPECT/MR imaging agent; copolymer; dual modality; hepatic asialoglycoprotein receptor; molecular imaging