title: [(124)I]FIAU: Human dosimetry and infection imaging in patients with suspected prosthetic joint infection.
abstract: BACKGROUND
  Fialuridine (FIAU) is a nucleoside analog that is a substrate for bacterial thymidine kinase (TK). Once phosphorylated by TK, [(124)I]FIAU becomes trapped within bacteria and can be detected with positron emission tomography/computed tomography (PET/CT). [(124)I]FIAU PET/CT has been shown to detect bacteria in patients with musculoskeletal bacterial infections. Accurate diagnosis of prosthetic joint infections (PJIs) has proven challenging because of the lack of a well-validated reference. In the current study, we assessed biodistribution and dosimetry of [(124)I]FIAU, and investigated whether [(124)I]FIAU PET/CT can diagnose PJIs with acceptable accuracy.
  
  
  METHODS
  To assess biodistribution and dosimetry, six subjects with suspected hip or knee PJI and six healthy subjects underwent serial PET/CT after being dosed with 74MBq (2mCi) [(124)I]FIAU intravenously (IV). Estimated radiation doses were calculated with the OLINDA/EXM software. To determine accuracy of [(124)I]FIAU, 22 subjects with suspected hip or knee PJI were scanned at 2-6 and 24-30h post IV injection of 185MBq (5mCi) [(124)I]FIAU. Images were interpreted by a single reader blinded to clinical information. Representative cases were reviewed by 3 additional readers. The utility of [(124)I]FIAU to detect PJIs was assessed based on the correlation of the patient's infection status with imaging results as determined by an independent adjudication board (IAB).
  
  
  RESULTS
  The kidney, liver, spleen, and urinary bladder received the highest radiation doses of [(124)I]FIAU. The effective dose was 0.16 to 0.20mSv/MBq and doses to most organs ranged from 0.11 to 0.76mGy/MBq. PET image quality obtained from PJI patients was confounded by metal artifacts from the prostheses and pronounced FIAU uptake in muscle. Consequently, a correlation with infection status and imaging results could not be established.
  
  
  CONCLUSIONS
  [(124)I]FIAU was well-tolerated in healthy volunteers and subjects with suspected PJI, and had acceptable dosimetry. However, the utility of [(124)I]FIAU for the clinical detection of PJIs is limited by poor image quality and low specificity.
authors.affiliation: BioMed Valley Discoveries Inc., Kansas City, Missouri. Electronic address: mzhang@biomed-valley.com.
authors.forename: Xiaoyan M
authors.initials: XM
authors.lastname: Zhang
authors.affiliation: BioMed Valley Discoveries Inc., Kansas City, Missouri.
authors.forename: Halle H
authors.initials: HH
authors.lastname: Zhang
authors.affiliation: Covance, Princeton, New Jersey.
authors.forename: Patrick
authors.initials: P
authors.lastname: McLeroth
authors.affiliation: Phoenix Clinical Research, Tamarac, Florida.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Berkowitz
authors.affiliation: The Rubin Institute for Advanced Orthopedics, Sinai Hospital, Baltimore, Maryland.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Mont
authors.affiliation: Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Stabin
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Barry A
authors.initials: BA
authors.lastname: Siegel
authors.affiliation: Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Abass
authors.initials: A
authors.lastname: Alavi
authors.affiliation: Mission Hospital, Ashville, North Carolina.
authors.forename: T Marc
authors.initials: TM
authors.lastname: Barnett
authors.affiliation: Covance, Princeton, New Jersey.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Gelb
authors.affiliation: Covance, Princeton, New Jersey.
authors.forename: Chantal
authors.initials: C
authors.lastname: Petit
authors.affiliation: Covance, Princeton, New Jersey.
authors.forename: John
authors.initials: J
authors.lastname: Spaltro
authors.affiliation: Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Steve Y
authors.initials: SY
authors.lastname: Cho
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
authors.affiliation: ICON Medical Imaging, Warrington, Pennsylvania.
authors.forename: James J
authors.initials: JJ
authors.lastname: Conklin
authors.affiliation: Department of Neurology, The Johns Hopkins Medical Institutes, Baltimore, Maryland.
authors.forename: Chetan
authors.initials: C
authors.lastname: Bettegowda
authors.affiliation: BioMed Valley Discoveries Inc., Kansas City, Missouri. Electronic address: ssaha@biomed-valley.com.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Saha
mesh_terms: D000328:Adult; D001086:Arabinofuranosyluracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007592:Joint Diseases / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D000072078:Positron Emission Tomography Computed Tomography / Q000009:adverse effects / Q000379:methods*; D016459:Prosthesis-Related Infections / Q000000981:diagnostic imaging* / Q000378:metabolism; D011874:Radiometry; D012449:Safety; D014018:Tissue Distribution
chemical_list: D001086:Arabinofuranosyluracil; C043457:fialuridine
keywords: Diagnosis; FIAU; PET/CT; Prosthetic joint infection