PURPOSE: (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. PROCEDURES: 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. CONCLUSION: 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.
PURPOSE: (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. PROCEDURES: 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. CONCLUSION: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: Vanessa L Cropley; Masahiro Fujita; John L Musachio; Jinsoo Hong; Subroto Ghose; Janet Sangare; Pradeep J Nathan; Victor W Pike; Robert B Innis Journal: J Nucl Med Date: 2006-01 Impact factor: 10.057
Authors: Noora M Scheinin; Tuula K Tolvanen; Ian A Wilson; Eveliina M Arponen; Kjell A Någren; Juha O Rinne Journal: J Nucl Med Date: 2007-01 Impact factor: 10.057
Authors: Ramin V Parsey; Marie-Jose Belanger; Gregory M Sullivan; Norman R Simpson; Michael G Stabin; Ronald Van Heertum; J John Mann Journal: J Nucl Med Date: 2005-04 Impact factor: 10.057
Authors: Marie-José Bélanger; Norman R Simpson; Theodore Wang; Ronald L Van Heertum; J John Mann; Ramin V Parsey Journal: Nucl Med Biol Date: 2004-11 Impact factor: 2.408
Authors: Koen Van Laere; Michel Koole; Sandra M Sanabria Bohorquez; Karolien Goffin; Ilonka Guenther; Marie J Belanger; Josee Cote; Paul Rothenberg; Inge De Lepeleire; Igor D Grachev; Richard J Hargreaves; Guy Bormans; H Donald Burns Journal: J Nucl Med Date: 2008-02-20 Impact factor: 10.057
Authors: David R Sprague; Masahiro Fujita; Yong Hoon Ryu; Jeih-San Liow; Victor W Pike; Robert B Innis Journal: Nucl Med Biol Date: 2008-05 Impact factor: 2.408
Authors: F Bretin; M A Bahri; C Bernard; G Warnock; J Aerts; N Mestdagh; T Buchanan; C Otoul; F Koestler; F Mievis; F Giacomelli; C Degueldre; R Hustinx; A Luxen; A Seret; A Plenevaux; E Salmon Journal: Mol Imaging Biol Date: 2015-08 Impact factor: 3.488
Authors: E M P Poels; L S Kegeles; J T Kantrowitz; M Slifstein; D C Javitt; J A Lieberman; A Abi-Dargham; R R Girgis Journal: Mol Psychiatry Date: 2013-10-29 Impact factor: 15.992
Authors: Lucas Rischka; Matej Murgaš; Verena Pichler; Chrysoula Vraka; Ivo Rausch; Dietmar Winkler; Lukas Nics; Sazan Rasul; Leo Robert Silberbauer; Murray Bruce Reed; Godber Mathis Godbersen; Jakob Unterholzner; Patricia Handschuh; Gregor Gryglewski; Thomas Mindt; Markus Mitterhauser; Andreas Hahn; Simon Mensah Ametamey; Wolfgang Wadsak; Rupert Lanzenberger; Marcus Hacker Journal: EJNMMI Res Date: 2022-08-26 Impact factor: 3.434