Biodistribution and radiation dosimetry of the glycine transporter-1 ligand 11C-GSK931145 determined from primate and human whole-body PET.
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.
Bullich
Santiago
S
Molecular Imaging Centre (CRC-CIM), Barcelona Biomedical Research Park, Barcelona, Spain. sbullich@crccorp.es
Slifstein
Mark
M
Passchier
Jan
J
Murthy
N Venkatesha
NV
Kegeles
Lawrence S
LS
Kim
Jong-Hoon
JH
Xu
Xiaoyan
X
Gunn
Roger N
RN
Herance
Raul
R
Gispert
Juan Domingo
JD
Gutiérrez
Antonio
A
Farré
Magí
M
Laruelle
Marc
M
Catafau
Ana M
AM
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
D001549:Benzamides; C561922:GSK 931145; D050487:Glycine Plasma Membrane Transport Proteins; D008024:Ligands; D011868:Radioisotopes