title: In Vivo 3-Dimensional Radiopharmaceutical-Excited Fluorescence Tomography.
abstract: Cerenkov luminescence imaging can image radiopharmaceuticals using a high-sensitivity charge-coupled device camera. However, Cerenkov luminescence emitted from the radiopharmaceuticals is weak and has low penetration depth in biologic tissues, which severely limits the sensitivity and accuracy of Cerenkov luminescence imaging. This study presents 3-dimensional (3D) radiopharmaceutical-excited fluorescence tomography (REFT) using europium oxide (EO) nanoparticles, which enhances the Cerenkov luminescence signal intensity, improves the penetration depth, and obtains more accurate 3D distribution of radiopharmaceuticals.
  
  
  METHODS
  The enhanced optical signals of various radiopharmaceuticals (including Na131I,18F-FDG,68GaCl3, Na99mTcO4) by EO nanoparticles were detected in vitro. The location and 3D distribution of the radiopharmaceuticals of REFT were then reconstructed and compared with those of Cerenkov luminescence tomography through the experiments with the phantom, artificial source-implanted mouse models, and mice bearing hepatocellular carcinomas.
  
  
  RESULTS
  The mixture of68GaCl3and EO nanoparticles possessed the strongest optical signals compared with the other mixtures. The in vitro phantom and implanted mouse studies showed that REFT revealed more accurate 3D distribution of68GaCl3REFT can detect more tumors than small-animal PET in hepatocellular carcinoma-bearing mice and achieved more accurate 3D distribution information than Cerenkov luminescence tomography.
  
  
  CONCLUSIONS
  REFT with EO nanoparticles significantly improves accuracy of localization of radiopharmaceuticals and can precisely localize the tumor in vivo.
authors.affiliation: Key Laboratory of Molecular Imaging of Chinese Academy of Sciences, Institute of Automation, Chinese Academy of Sciences, Beijing, China.|The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Mingxuan
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, General Hospital of Chinese Armed Police Forces, Beijing, China; and.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Department of Nuclear Medicine, Chinese PLA General Hospital, Beijing, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Mingru
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Imaging of Chinese Academy of Sciences, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
authors.forename: Muhan
authors.initials: M
authors.lastname: Liu
authors.affiliation: Key Laboratory of Molecular Imaging of Chinese Academy of Sciences, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Guo
authors.affiliation: Key Laboratory of Molecular Imaging of Chinese Academy of Sciences, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
authors.forename: Zeyu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China yangwd1971@163.com tian@ieee.org.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China yangwd1971@163.com tian@ieee.org.
authors.forename: Weidong
authors.initials: W
authors.lastname: Yang
authors.affiliation: Key Laboratory of Molecular Imaging of Chinese Academy of Sciences, Institute of Automation, Chinese Academy of Sciences, Beijing, China yangwd1971@163.com tian@ieee.org.|The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tian
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000000981:diagnostic imaging*; D045744:Cell Line, Tumor; D007089:Image Enhancement / Q000379:methods; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008297:Male; D053768:Metal Nanoparticles / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence / Q000295:instrumentation / Q000379:methods*; D057054:Molecular Imaging / Q000295:instrumentation / Q000379:methods*; D019047:Phantoms, Imaging; D049268:Positron-Emission Tomography / Q000295:instrumentation / Q000379:methods*; D019275:Radiopharmaceuticals / Q000032:analysis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D041622:Tomography, Optical / Q000295:instrumentation / Q000379:methods; D051598:Whole Body Imaging / Q000295:instrumentation / Q000379:methods
chemical_list: D019275:Radiopharmaceuticals
keywords: Cerenkov luminescence imaging (CLI); PET; hepatocellular carcinoma (HCC); radionuclides; radiopharmaceutical excitation fluorescence tomography (REFT)