title: Biodistribution and radiation dosimetry of the glycine transporter-1 ligand 11C-GSK931145 determined from primate and human whole-body PET.
abstract: OBJECTIVE
  (11)C-GSK931145 is a novel radioligand suitable for imaging the glycine transporter 1 (GlyT-1) in brain. In the present study, human dosimetry is estimated from baboon and human biodistribution data.
  
  
  METHODS
  Three baboons and eight healthy human volunteers underwent whole-body positron emission tomography (PET) scans. Human dosimetry was estimated using three different region-of-interest (ROI) delineation methods that ranged in their complexity and execution time: ROIs drawn on anterior-posterior compressed PET images, on subsamples of the organs, and covering the whole-organ. Residence times for each organ were calculated as the area under the time-activity curves divided by the injected activity. Radiation dose estimates were calculated from organ residence times using the OLINDA/EXM software package.
  
  
  RESULTS
  The overall distribution of activity was similar in baboons and humans. Early scans presented high activity in the liver, and moderate activity in the lungs and kidneys. The principal route of clearance was intestinal and no urinary excretion was observed. The limiting organ with the highest radiation-absorbed dose was the liver. The mean effective dose in humans was 4.02 μSv/MBq (male phantom) and 4.95 μSv/MBq (female phantom) (ROIs drawn on subsamples of the organs). The human effective dose estimated from baboon data was ~15% larger than the effective dose estimated from human data.
  
  
  CONCLUSIONS
  Human PET imaging of the glycine transporter-1 with (11)C-GSK931145 results in a moderate effective human radiation dose, which allows for multiple PET examinations in the same individual. Among the three methods compared to delineate ROIs, the organ subsampling method shows the best balance between quantitative accuracy and practical application.
authors: Molecular Imaging Centre (CRC-CIM), Barcelona Biomedical Research Park, Barcelona, Spain. sbullich@crccorp.es
authors: Santiago
authors: S
authors: Bullich
authors: Mark
authors: M
authors: Slifstein
authors: Jan
authors: J
authors: Passchier
authors: N Venkatesha
authors: NV
authors: Murthy
authors: Lawrence S
authors: LS
authors: Kegeles
authors: Jong-Hoon
authors: JH
authors: Kim
authors: Xiaoyan
authors: X
authors: Xu
authors: Roger N
authors: RN
authors: Gunn
authors: Raul
authors: R
authors: Herance
authors: Juan Domingo
authors: JD
authors: Gispert
authors: Antonio
authors: A
authors: Gutiérrez
authors: Magí
authors: M
authors: Farré
authors: Marc
authors: M
authors: Laruelle
authors: Ana M
authors: AM
authors: Catafau
mesh_terms: D000042:Absorption; D000328:Adult; D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D050487:Glycine Plasma Membrane Transport Proteins / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity; D010215:Papio / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D011868:Radioisotopes / Q000493:pharmacokinetics*; D011874:Radiometry / Q000379:methods*; D013997:Time Factors; D014018:Tissue Distribution; D014915:Whole-Body Counting; D055815:Young Adult
chemical_list: D001549:Benzamides; C561922:GSK 931145; D050487:Glycine Plasma Membrane Transport Proteins; D008024:Ligands; D011868:Radioisotopes