title: Biodistribution and Radiation Dosimetry for the Novel SV2A Radiotracer [(18)F]UCB-H: First-in-Human Study.
abstract: OBJECTIVE
  [(18)F]UCB-H is a novel radiotracer with a high affinity for synaptic vesicle glycoprotein 2A (SV2A), a protein expressed in synaptic vesicles. SV2A is the binding site of levetiracetam, a "first-in-class" antiepileptic drug with a distinct but still poorly understood mechanism of action. The objective of this study was to determine the biodistribution and radiation dosimetry of [(18)F]UCB-H in a human clinical trial and to establish injection limits according to biomedical research guidelines. Additionally, the clinical radiation dosimetry results were compared to estimations in previously published preclinical data.
  
  
  METHODS
  Dynamic whole body positron emission tomography/X-ray computed tomography (PET/CT) imaging was performed over approximately 110 min on five healthy male volunteers after injection of 144.5 ± 7.1 MBq (range, 139.1-156.5 MBq) of [(18)F]UCB-H. Major organs were delineated on CT images, and time-activity curves were obtained from co-registered dynamic PET emission scans. The bladder could only be delineated on PET images. Time-integrated activity coefficients were calculated as area under the curve using trapezoidal numerical integration. Urinary excretion data based on PET activities including voiding was also simulated using the dynamic bladder module of OLINDA/EXM. The radiation dosimetry was calculated using OLINDA/EXM.
  
  
  RESULTS
  The effective dose to the OLINDA/EXM 70-kg standard male was 1.54 × 10(-2) ± 6.84 × 10(-4) millisieverts (mSv)/MBq, with urinary bladder wall, gallbladder wall, and the liver receiving the highest absorbed dose. The brain, the tracer's main organ of interest, received an absorbed dose of 1.89 × 10(-2) ± 2.32 × 10(-3) mGy/MBq.
  
  
  CONCLUSIONS
  This first human dosimetry study of [(18)F]UCB-H indicated that the tracer shows similar radiation burdens to widely used common clinical tracers. Single injections of at maximum 672 MBq for US practice and 649 MBq for European practice keep radiation exposure below recommended limits. Recently published preclinical dosimetry data extrapolated from mice provided satisfactory prediction of total body and effective dose but showed significant differences in organ absorbed doses compared to human data.
authors.affiliation: Cyclotron Research Centre, University of Liège, Allée du 6 Août, Sart Tilman B30, 4000, Liège, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Bretin
authors.forename: M A
authors.initials: MA
authors.lastname: Bahri
authors.forename: C
authors.initials: C
authors.lastname: Bernard
authors.forename: G
authors.initials: G
authors.lastname: Warnock
authors.forename: J
authors.initials: J
authors.lastname: Aerts
authors.forename: N
authors.initials: N
authors.lastname: Mestdagh
authors.forename: T
authors.initials: T
authors.lastname: Buchanan
authors.forename: C
authors.initials: C
authors.lastname: Otoul
authors.forename: F
authors.initials: F
authors.lastname: Koestler
authors.forename: F
authors.initials: F
authors.lastname: Mievis
authors.forename: F
authors.initials: F
authors.lastname: Giacomelli
authors.forename: C
authors.initials: C
authors.lastname: Degueldre
authors.forename: R
authors.initials: R
authors.lastname: Hustinx
authors.forename: A
authors.initials: A
authors.lastname: Luxen
authors.forename: A
authors.initials: A
authors.lastname: Seret
authors.forename: A
authors.initials: A
authors.lastname: Plenevaux
authors.forename: E
authors.initials: E
authors.lastname: Salmon
mesh_terms: D000818:Animals; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D011725:Pyridines / Q000493:pharmacokinetics*; D011760:Pyrrolidinones / Q000493:pharmacokinetics*; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D051598:Whole Body Imaging / Q000379:methods
chemical_list: D005462:Fluorine Radioisotopes; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D011725:Pyridines; D011760:Pyrrolidinones; D019275:Radiopharmaceuticals; C000599325:UCB-H compound; C076414:SV2A protein, human