title: Dosimetry of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 in rodents, pigs, non-human primates and human - repeated scanning in human is possible.
abstract: Quantitative PET imaging with [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 has potential use in diabetes and cancer. However, the radiation dose to the kidneys has been a concern for the possibility of repeated imaging studies in humans. Therefore, we investigated the dosimetry of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 based on the biodistribution data in rats, pigs, non-human primates (NHP) and a human.Organ distribution of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 in rats (Male Lewis; n=12; 30, 60, and 80 min) was measured ex vivo. The dynamic uptake of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 in the abdomen was assessed by PET/CT scanning of pigs (male; n = 4, 0-60 min), NHP (Female; cynomolgus; n=3; 0-90 min), and human (female; n=1; 0-40, 100, 120 min).The organ distribution data in each species were extrapolated to those of a human, assuming similar distribution between the species. Residence times were assessed by trapezoidal approximation of the kinetic data. Organ doses (mGy/MBq) and the whole body effective dose (mSv/MBq), was extrapolated by using the OLINDA/EXM 1.1 software. The extrapolated human whole body effective dose was 0.017 ± 0.004 (rats), 0.014 ± 0.004 (pigs), 0.017 ± 0.004 (NHP), and 0.016 (human) mSv/MBq. The absorbed dose to the kidneys was limiting:0.33 ± 0.06 (rats), 0.28±0.05 (pigs), 0.65 ± 0.11 (NHP), and 0.28 (human) mGy/MBq, which corresponded to the maximum yearly administered amounts of 455 (rat), 536 (pig), 231 (NHP), and 536 (human) MBq before reaching the yearly kidney limiting dose of 150 mGy. More than 200 MBq of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 can be administered yearly in a human, allowing for repeated (2-4 times) scanning. This potentially enables longitudinal clinical PET imaging studies of the GLP-1R in the pancreas, transplanted islets, or insulinoma.
authors.affiliation: Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University Uppsala, Sweden.
authors.forename: Ram Kumar
authors.initials: RK
authors.lastname: Selvaraju
authors.affiliation: Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University Uppsala, Sweden.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Bulenga
authors.affiliation: Department of Medical Cell Biology, Uppsala University Uppsala, Sweden ; Department of Medical Sciences, Uppsala University Uppsala, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Espes
authors.affiliation: Department of Surgical Sciences, Radiology, Uppsala University Uppsala, Sweden ; PET Centre, Centre for Medical Imaging, Uppsala University Hospital Uppsala, Sweden.
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
authors.affiliation: PET Centre, Centre for Medical Imaging, Uppsala University Hospital Uppsala, Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Sörensen
authors.affiliation: Department of Medical Sciences, Uppsala University Uppsala, Sweden.
authors.forename: Barbro
authors.initials: B
authors.lastname: Eriksson
authors.affiliation: Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University Uppsala, Sweden.
authors.forename: Sergio
authors.initials: S
authors.lastname: Estrada
authors.affiliation: Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University Uppsala, Sweden ; Department of Surgical Sciences, Radiology, Uppsala University Uppsala, Sweden ; PET Centre, Centre for Medical Imaging, Uppsala University Hospital Uppsala, Sweden.
authors.forename: Irina
authors.initials: I
authors.lastname: Velikyan
authors.affiliation: Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University Uppsala, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Eriksson
keywords: Dosimetry; GLP-1R; PET; [68Ga]Ga-DO3A-VS-Cys40-Exendin-4; insulinoma; islet imaging