title: Synthesis and preliminary evaluation of a99mTc-labeled folate-PAMAM dendrimer for FR imaging.
abstract: Folate receptor is an ideal target for tumor-specific diagnostic and therapeutic. The aim of this study was to synthesize99mTc-labeled folate-polyamidoamine dendrimer modified with 2-hydrazinonicotinic acid (99mTc-HP3FA) for FR imaging. The99mTc-HP3FA conjugate was prepared using N-tris-(hydroxymethyl)-methylglycine and trisodium triphenylphosphine-3,3',3″-trisulfonate as coligands. Physicochemical properties, in vitro cell uptake study, and in vivo micro-single-photon emission computed tomography/CT imaging were performed. The radiolabeled99mTc-HP3FA conjugate was prepared with high radiolabeling yield, good stability, and water solubility (logP = -1.70 ± 0.21). In cell uptake study, the radiolabeled conjugate showed high uptakes in the FR-abundant KB cells and could be blocked significantly by excess folic acid. The 7721 cells which served as control group substantially had no uptakes. The results of micro-single-photon emission computed tomography/CT imaging exhibited that high accumulation of activity was found in FR-overexpressed KB tumor, and the tumor-to-muscle ratio was approximately 25.78, while, using free FA as inhibitor, the uptakes of99mTc-HP3FA in KB tumor and kidney were obviously inhibited. In summary, a new radiocompound was synthesized successfully with specific FR targeting ability. The feasibility of99mTc-HP3FA for early diagnosis of FR-positive tumors with non-invasive single-photon emission computed tomography imaging was demonstrated and the possibility of imaging-guided drug delivery based on multifunctional polyamidoamine will be studied in the future.
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: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.|Department of Isotope, China Institute of Atomic Energy, Beijing, 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: Mengna
authors.initials: M
authors.lastname: Gao
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: Changrong
authors.initials: C
authors.lastname: Shi
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: Duo
authors.initials: D
authors.lastname: Xu
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: Linyi
authors.initials: L
authors.lastname: You
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: Xiaowei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital Affiliated of Xiamen University, Xiamen, China.
authors.forename: Xinhui
authors.initials: X
authors.lastname: Su
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: Department of Nuclear Medicine, the Affiliated Hospital of Hainan Medical College, Haikou, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Pan
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: Ting
authors.initials: T
authors.lastname: Liu
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: Xianzhong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry*; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000000981:diagnostic imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D013667:Technetium / Q000737:chemistry; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D014183:Transplantation, Heterologous
chemical_list: D050091:Dendrimers; C104700:PAMAM Starburst; D019275:Radiopharmaceuticals; D013667:Technetium; D005492:Folic Acid
keywords: KB tumor-bearing mice; PAMAM dendrimer; SPECT imaging; folate receptor; technetium-99m