title: Automated PET Radiotracer Manufacture on the BG75 System and Imaging Validation Studies of [18F]fluoromisonidazole ([18F]FMISO).
abstract: OBJECTIVE
  The hypoxia PET tracer, 1-[18F]fluoro-3-(2-nitro-1Himidazol- 1-yl)-propan-2-ol ([18F]FMISO) is the first radiotracer developed for hypoxia PET imaging and has shown promising for cancer diagnosis and prognosis. However, access to [18F]FMISO radiotracer is limited due to the needed cyclotron and radiochemistry expertise. The study aimed to develop the automated production method on the [18F]FMISO radiotracer with the novel fully automated platform of the BG75 system and validate its usage on animal tumor models.
  
  
  METHODS
  [18F]FMISO was produced with the dose synthesis cartridge automatically on the BG75 system. Validation of [18F]FMISO hypoxia imaging functionality was conducted on two tumor mouse models (FaDu/U87 tumor). The distribution of [18F]FMISO within tumor was further validated by the standard hypoxia marker EF5.
  
  
  RESULTS
  The average radiochemical purity was (99±1) % and the average pH was 5.5±0.2 with other quality attributes passing standard criteria (n=12). Overall biodistribution for [18F]FMISO in both tumor models was consistent with reported studies where bladder and large intestines presented highest activity at 90 min post injection. High spatial correlation was found between [18F]FMISO autoradiography and EF5 hypoxia staining, indicating high hypoxia specificity of [18MF]FMISO.
  
  
  CONCLUSIONS
  This study shows that qualified [18F]FMISO can be efficiently produced on the BG75 system in an automated "dose-on-demand" mode using single dose disposable cards. The possibilities of having a low-cost, automated system manufacturing ([18F]Fluoride production + synthesis + QC) different radiotracers will greatly enhance the potential for PET technology to reach new geographical areas and underserved patient populations.
authors: University of North Carolina at Chapel Hill, Campus box #7513, Chapel Hill, NC 27599, USA.
authors: Hong
authors: H
authors: Yuan
authors: Jonathan E
authors: JE
authors: Frank
authors: Joseph R
authors: JR
authors: Merrill
authors: Daniel A
authors: DA
authors: Hillesheim
authors: Mark H
authors: MH
authors: Khachaturian
authors: ABT Molecular Imaging Inc., 3024 Topside Business Park Dr., Louisville, TN 37777, USA.
authors: Atilio I
authors: AI
authors: Anzellotti
mesh_terms: D000818:Animals; D001345:Autoradiography; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D005909:Glioblastoma / Q000000981:diagnostic imaging*; D006801:Humans; D051379:Mice; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000072078:Positron Emission Tomography Computed Tomography; D011857:Radiographic Image Interpretation, Computer-Assisted; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000494:pharmacology*; D014018:Tissue Distribution
chemical_list: D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D008920:Misonidazole
keywords: PET; [18F]FMISO; hypoxia; solid-phase extraction; system BG75; tumor hypoxia.