Biodistribution and Radiation Dosimetry of the Serotonin 5-HT6 Ligand [11C]GSK215083 Determined from Human Whole-Body PET
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We measured the whole-body distribution of IV-injected [11C]GSK215083, a new 5-HT6 antagonist PET tracer, as a function of time in adult subjects, in order to determine the radiation exposure.
After injection with a single bolus of [11C]GSK215083 (range 330–367 MBq; mean 346 MBq), PET emission data were acquired for approximately 120 min in six subjects (three males and three females). Five organs were identified as exhibiting uptake above background. For these, regions of interest were delineated on emission images, and time–activity curves (TAC) generated. Residence times were calculated as the area under the curve of the TAC, normalized to injected activities and standard values of organ volumes. Dosimetry calculations were then performed using the computer program OLINDA/EXM 1.0.
The mean effective dose averaged over both males and females (±standard deviation) was estimated to be 7.7 ± 1.0 μSv/MBq (male 7.0 ± 0.4; female 8.5 ± 0.6). For the effective dose equivalent, the corresponding values are 7.8 ± 1.2 μSv/MBq (male 6.8 ± 0.5; female 8.9 ± 0.1). The organ receiving the highest dose was the lung, with an average equivalent dose of 25.6 ± 6.9 μSv/MBq (male 20.8 ± 5.6; female 30.4 ± 4.4).
The estimated radiation dose for [11C]GSK215083 is consistent with those for other neuroreceptor ligands labeled with carbon-11. The somewhat higher dose estimate for females compared to males may reflect the difference in observed residence times and representative differences in the male and female phantoms used for dosimetry calculations. Based on conventionally accepted dose limits, [11C]GSK215083 may be used for multiple PET scans in the same subject.
Key wordsBiodistribution Dosimetry Positron emission tomography [11C]GSK215083 5-HT6 antagonist
The authors would like to gratefully acknowledge the help of the following staff at the CAMH PET center who were instrumental in conducting this piece of work: Peter Bloomfield, Jeannie Fong, Armando Garcia, Winston Stableford, and Min Wong. In addition we would like to acknowledge the support of Jan Passchier of GlaxoSmithKline for the many helpful conversations over the years concerning the role of radiation protection in our research studies.
Conflict of Interest
At the time this work was conducted. RAC, CS, WH, NK, EAR and ML were employees of and owners of stock/options in GlaxoSmithKline. AAW and SH have received grants from GlaxoSmithKline.
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