Dosimetry and pharmacokinetics of 177LuLu-satoreotide tetraxetan in patients with progressive neuroendocrine tumours

To evaluate the dosimetry and pharmacokinetics of the novel radiolabelled somatostatin receptor antagonist 177LuLu-satoreotide tetraxetan in patients with advanced neuroendocrine tumours (NETs). This study was part of a phase I/II trial of 177LuLu-satoreotide tetraxetan, administered at a median cumulative activity of 13.0 GBq over three planned cycles (median activity/cycle: 4.5 GBq), in 40 patients with progressive NETs. Organ absorbed doses were monitored at each cycle using patient-specific dosimetry; the cumulative absorbed-dose limits were set at 23.0 Gy for the kidneys and 1.5 Gy for bone marrow. Absorbed dose coefficients (ADCs) were calculated using both patient-specific and model-based dosimetry for some patients. In all evaluated organs, maximum 177LuLu-satoreotide tetraxetan uptake was observed at the first imaging timepoint (4 h after injection), followed by an exponential decrease. Kidneys were the main route of elimination, with a cumulative excretion of 57-66% within 48 h following the first treatment cycle. At the first treatment cycle, 177LuLu-satoreotide tetraxetan showed a median terminal blood half-life of 127 h and median ADCs of 177LuLu-satoreotide tetraxetan were 5.0 Gy/GBq in tumours, 0.1 Gy/GBq in the bone marrow, 0.9 Gy/GBq in kidneys, 0.2 Gy/GBq in the liver and 0.8 Gy/GBq in the spleen. Using image-based dosimetry, the bone marrow and kidneys received median cumulative absorbed doses of 1.1 and 10.8 Gy, respectively, after three cycles. 177LuLu-satoreotide tetraxetan showed a favourable dosimetry profile, with high and prolonged tumour uptake, supporting its acceptable safety profile and promising efficacy. NCT02592707. Registered October 30, 2015.