Dosimetry of [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 in rat, non-human primate and human

Objectives Quantitative PET imaging with Exendin-4 analogues have potential use in cancer and diabetes as well as in the development of novel pharmaceuticals targeting glucagon like peptide-1 receptor (GLP-1R).Selective binding of [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 to GLP-1R in insulinoma and in the pancreas in vivo has been reported earlier[1,2]. However, the radiation dose to the kidneys has been a concern for the possibility of repeated imaging studies in humans. Here, the dosimetry of [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 in rats, non-human primate and human was investigated.

Methods The dynamic uptake of (68Ga)Ga-DO3A-VS-Cys40-Exendin-4 in the abdomen was assessed by PET/CT scanning of non-human primates (NHP, cynomolgus; n=4; 0-90 min) and human (female; n=1; 0-35, 60, 120 min), and by post mortem organ distribution studies in rats (Male Lewis; n=12; 30, 60 and 80 min). Organ doses (mSv/MBq) and the administered dose (MBq) required to reach the yearly acceptable organ dose in humans was extrapolated by using the OLINDA software.

Results The whole body effective dose was 0.0112 mSv/MBq (rat and NHP) or 0.0138 mSv/MBq based on clinical data (corresponding to a maximum yearly administered amount of 725 MBq). The local dose to kidneys was limiting - 0.246 (rat), 0.748 (NHP) and 0.543 (human) mSv/MBq, which corresponded to maximum yearly administered amounts of 610 (rat), 201 (NHP) and 276 (human) MBq. The expected administered dose is expected to fall in the range of 50-100 MBq based on a specific radioactivity of 50-100 MBq/nmol.

Conclusions [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 can be administered repeatedly (2-4 times) yearly also in healthy volunteers without reaching limiting radiation doses in the kidneys. This potentially enables longitudinal clinical PET imaging studies of the GLP-1R in pancreas or transplanted islets.

Research Support Barndiabetesfonden, ExoDiab.