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Radiation Dosimetry of a Novel Adenosine A 2A Receptor Radioligand [ 11 C]Preladenant Based on PET/CT Imaging and Ex Vivo Biodistribution in Rats.
Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging 2017 April
PURPOSE: [11 C]Preladenant was developed as a novel adenosine A2A receptor PET radioligand. The aim of this study was to determine the radiation dosimetry of [11 C]preladenant and to investigate whether dosimetry estimation based on organ harvesting can be replaced by positron emission tomography (PET)/x-ray computed tomography (CT) imaging in rats.
PROCEDURES: Male Wistar rats (n = 35) were i.v. injected with [11 C]preladenant. The tracer biodistribution was determined by organ harvesting at 1, 5, 15, 30, 60, and 90 min post injection. Hollow organs including the stomach, intestines, and urinary bladder were harvested with contents. In 10 rats, a 90-min dynamic PET/CT scan of the torso was acquired. Twenty volumes of interest (VOIs) were manually drawn on the PET image using the CT image of the same animal as anatomical reference. The dynamic time-activity curves were used to calculate organ residence times (RTs). Human radiation dosimetry estimates, derived from rat data, were calculated with OLINDA/EXM 1.1.
RESULTS: PET-imaging and organ-harvesting estimated comparable organ RTs, with differences of 6-27 %, except for the lungs, pancreas, and urinary bladder, with differences of 48, 53, and 60, respectively. The critical organ was the small intestine with a dose of 25 μSv/MBq. The effective doses (EDs) calculated from imaging-based and organ-harvesting-derived data were 5.5 and 5.6 μSv/MBq, respectively, using the International Commission on Radiological Protection 60 tissue weighting factors.
CONCLUSIONS: The ED of [11 C]preladenant (2 mSv for a 370-MBq injected dose) is comparable with other C-11-labeled PET tracers. Estimation of the radiation dosimetry of [11 C]preladenant by PET/CT imaging in rats is feasible and gives comparable results to organ harvesting, provided that small VOIs are used and the content of hollow organs is taken into account. Dosimetry by PET imaging can strongly reduce the number of laboratory animals required.
PROCEDURES: Male Wistar rats (n = 35) were i.v. injected with [11 C]preladenant. The tracer biodistribution was determined by organ harvesting at 1, 5, 15, 30, 60, and 90 min post injection. Hollow organs including the stomach, intestines, and urinary bladder were harvested with contents. In 10 rats, a 90-min dynamic PET/CT scan of the torso was acquired. Twenty volumes of interest (VOIs) were manually drawn on the PET image using the CT image of the same animal as anatomical reference. The dynamic time-activity curves were used to calculate organ residence times (RTs). Human radiation dosimetry estimates, derived from rat data, were calculated with OLINDA/EXM 1.1.
RESULTS: PET-imaging and organ-harvesting estimated comparable organ RTs, with differences of 6-27 %, except for the lungs, pancreas, and urinary bladder, with differences of 48, 53, and 60, respectively. The critical organ was the small intestine with a dose of 25 μSv/MBq. The effective doses (EDs) calculated from imaging-based and organ-harvesting-derived data were 5.5 and 5.6 μSv/MBq, respectively, using the International Commission on Radiological Protection 60 tissue weighting factors.
CONCLUSIONS: The ED of [11 C]preladenant (2 mSv for a 370-MBq injected dose) is comparable with other C-11-labeled PET tracers. Estimation of the radiation dosimetry of [11 C]preladenant by PET/CT imaging in rats is feasible and gives comparable results to organ harvesting, provided that small VOIs are used and the content of hollow organs is taken into account. Dosimetry by PET imaging can strongly reduce the number of laboratory animals required.
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