Dosimetry and pharmacokinetics of [177Lu]Lu-satoreotide tetraxetan in patients with progressive neuroendocrine tumours

• Published in: European journal of nuclear medicine and molecular imaging 2024-07, Vol.51 (8), p.2428-2441
• Main Authors: Schürrle, Seval Beykan, Eberlein, Uta, Ansquer, Catherine, Beauregard, Jean-Mathieu, Durand-Gasselin, Lucie, Grønbæk, Henning, Haug, Alexander, Hicks, Rodney J., Lenzo, Nat P., Navalkissoor, Shaunak, Nicolas, Guillaume P., Pais, Ben, Volteau, Magali, Wild, Damian, McEwan, Alexander, Lassmann, Michael
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Bone marrow; Bone tumors; Cardiology; Disease Progression; Dosimeters; Dosimetry; Female; Humans; Imaging; Kidneys; Lutetium - pharmacokinetics; Lutetium isotopes; Male; Medicine; Medicine & Public Health; Middle Aged; Neuroendocrine tumors; Neuroendocrine Tumors - diagnostic imaging; Neuroendocrine Tumors - metabolism; Neuroendocrine Tumors - radiotherapy; Nuclear Medicine; Octreotide - analogs & derivatives; Octreotide - pharmacokinetics; Octreotide - therapeutic use; Oncology; Original; Original Article; Orthopedics; Patients; Pharmacokinetics; Radioisotopes; Radiology; Radiometry; Radiopharmaceuticals - pharmacokinetics; Radiopharmaceuticals - therapeutic use; Somatostatin; Somatostatin - analogs & derivatives; Somatostatin - pharmacokinetics; Tissue Distribution; Tumors
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-024-06682-1

Purpose To evaluate the dosimetry and pharmacokinetics of the novel radiolabelled somatostatin receptor antagonist [ 177 Lu]Lu-satoreotide tetraxetan in patients with advanced neuroendocrine tumours (NETs). Methods This study was part of a phase I/II trial of [ 177 Lu]Lu-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. Results In all evaluated organs, maximum [ 177 Lu]Lu-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, [ 177 Lu]Lu-satoreotide tetraxetan showed a median terminal blood half-life of 127 h and median ADCs of [ 177 Lu]Lu-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. Conclusion [ 177 Lu]Lu-satoreotide tetraxetan showed a favourable dosimetry profile, with high and prolonged tumour uptake, supporting its acceptable safety profile and promising efficacy. Trial registration NCT02592707. Registered October 30, 2015.