Abstract
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Objectives The present work explores the long term toxicity of 177Lu-tetraxetan-tetulomab in nude mice.
Methods Two in-vivo long term toxicity experiments were performed using institutionally bred male and female Balb/C nu/nu (NCR). In the first experiment the mice were treated with a single administration of 0.9% NaCl, 50 or 100 MBq/kg of 177Lu-tetraxetan-tetulomab and monitored for 10 months. When no toxicity was observed with regards to body weight and blood counts during the first month, a second experiment was started with dosing of 150 and 250 MBq/kg 177Lu-tetraxetan-tetulomab. Half of these mice were followed for 6 months and half for 10 months. Blood cells and clinical chemistry were measured every month and body weight was measured twice a week. The mice were necropsied and organs were examined by pathologist.
Results The blood values were within normal ranges for nude mice for all time points in both experiments and there were no dosage dependent decrease in white and red blood cells or platelets. The clinical chemistry parameters alkaline phosphatase (ALP), alanine transaminase (GPT), aspartate transaminase (GOT) and urea were within normal ranges in all groups for all time points. There were no significant differences in body weight or survival between the groups. Ovaries, spleen and bone marrow were identified as main target organs by histopathology studies. Ovaries and spleen were predominately affected in the 150 and 250 MBq/kg groups while in the bone marrow histological changes occurred only in the 250 MBq/kg group.
Conclusions The MTD of 177Lu-tetraxetan-tetulomab for nude mice was above 250 MBq/kg. Spleen, bone marrow and ovaries were identified as the main affected organs.