title: Prospective Study of (68)Ga-NOTA-NFB: Radiation Dosimetry in Healthy Volunteers and First Application in Glioma Patients.
abstract: OBJECTIVE
  The chemokine receptor CXCR4 is overexpressed in various types of human cancers. As a specific imaging agent of CXCR4, (68)Ga-NOTA-NFB was investigated in this study to assess its safety, biodistribution and dosimetry properties in healthy volunteers, and to preliminarily evaluate its application in glioma patients.
  
  
  METHODS
  Six healthy volunteers underwent whole-body PET scans at 0, 0.5, 1, 2 and 3 h after (68)Ga-NOTA-NFB injection (mean dose, 182.4 ± 3.7 MBq (4.93 ± 0.10 mCi)). For time-activity curve calculations, 1 mL blood samples were obtained at 1, 3, 5, 10, 30, 60, 90, 120, 150 and 180 min after the injection. The estimated radiation doses were calculated by OLINDA/EXM software. Eight patients with glioma were enrolled and underwent both (68)Ga-NOTA-NFB and (18)F-FDG PET/CT scans before surgery. The expression of CXCR4 on the resected brain tumor tissues was determined by immunohistochemical staining.
  
  
  RESULTS
  (68)Ga-NOTA-NFB was safe and well tolerated by all subjects. A rapid activity clearance from the blood circulation was observed. The organs with the highest absorbed doses were spleen (193.8 ± 32.5 μSv/MBq) and liver (119.3 ± 25.0 μSv/MBq). The mean effective dose was 25.4 ± 6.1 μSv/MBq. The maximum standardized uptake values (SUVmax) and the maximum target to non-target ratios (T/NTmax) of (68)Ga-NOTA-NFB PET/CT in glioma tissues were 4.11 ± 2.90 (range, 0.45-8.21) and 9.21 ± 8.75 (range, 3.66-24.88), respectively, while those of (18)F-FDG PET/CT were 7.34 ± 2.90 (range, 3.50-12.27) and 0.86 ± 0.41 (range, 0.35-1.59). The histopathological staining confirmed that CXCR4 was overexpressed on resected tumor tissues with prominent (68)Ga-NOTA-NFB uptake.
  
  
  CONCLUSIONS
  With a favorable radiation dosimetry profile, (68)Ga-NOTA-NFB is safe for clinical imaging. Compared to (18)F-FDG PET/CT, (68)Ga-NOTA-NFB PET/CT is more sensitive in detecting glioma and could have potential in diagnosing and treatment planning for CXCR4 positive patients.
authors.affiliation: 1. Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: 1. Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Mingru
authors.initials: M
authors.lastname: Zhang
authors.affiliation: 2. Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: 1. Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Shengjun
authors.initials: S
authors.lastname: Wang
authors.affiliation: 1. Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Kang
authors.affiliation: 1. Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Guoquan
authors.initials: G
authors.lastname: Li
authors.affiliation: 3. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland 20892, United States.
authors.forename: Orit
authors.initials: O
authors.lastname: Jacobson
authors.affiliation: 3. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland 20892, United States.
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.affiliation: 1. Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Yang
authors.affiliation: 1. Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: 3. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland 20892, United States.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005710:Gallium Radioisotopes / Q000008:administration & dosage*; D005910:Glioma / Q000175:diagnosis*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D011446:Prospective Studies; D011874:Radiometry / Q000379:methods*; D019718:Receptors, CXCR4 / Q000032:analysis*
chemical_list: C527276:CXCR4 protein, human; D005710:Gallium Radioisotopes; D019718:Receptors, CXCR4
keywords: 68Ga-NOTA-NFB; CXCR4; PET/CT; glioma; internal dosimetry