Emil Schüler1, Andreas Österlund1, Eva Forssell-Aronsson1,2. 1. a Department of Radiation Physics , Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy at the University of Gothenburg , Gothenburg , Sweden. 2. b Department of Medical Physics and Biomedical Engineering , Sahlgrenska University Hospital , Gothenburg , Sweden.
Abstract
BACKGROUND: (177)Lu-octreotate therapy has proven to give favorable results after treatment of patients with neuroendocrine tumors. Much focus has been on the binding and uptake of (177)Lu-octreotate in tumor tissue, but biodistribution properties in normal tissues is still not fully understood, and the effect of receptor saturation may be important. The aim of this study was to investigate the influence of the amount of (177)Lu-octreotate on the biodistribution of (177)Lu-octreotate in normal tissues in mice. MATERIAL AND METHODS: C57BL/6N female mice were intravenously injected with 0.1-150 MBq (177)Lu-octreotate (0.039 μg peptide/MBq). The mice were killed 0.25 h to 14 days after injection by cardiac puncture under anesthesia. Activity concentration was determined in blood, bone marrow, kidneys, liver, lungs, pancreas, and spleen, and mean absorbed doses were calculated. RESULTS: The activity concentration varied with time and amount of injected activity. At 4-8 h after injection, a local maximum in activity concentration was found for liver, lungs, pancreas, and spleen. With the exception for the lower injected activities (0.1-1 MBq), the overall highest uptake was found in the kidneys (%IA/g). Large variations were found and the activity concentration in kidneys was 11-23%IA/g at 4 h, and 0.22-1.9%IA/g at 7 days after injection. Furthermore, a clear reduction in activity concentration with increased injected activity was observed for lungs, pancreas and spleen. CONCLUSION: The activity concentration in all tissues investigated was strongly influenced by the amount of (177)Lu-octreotate injected. Large differences in mean absorbed dose per unit injected activity were found between low (0.1-1 MBq, 0.0039-0.039 μg) and moderate amounts (5-45 MBq, 0.2-1.8 μg). Furthermore, the results clearly showed the need for better ways to estimate absorbed dose to bone marrow other than methods based on a single blood sample analysis. Since the absorbed dose to critical organs will limit the amount of (177)Lu-octreotate administered, these findings must be taken into consideration when optimizing this type of therapy.
BACKGROUND: (177)Lu-octreotate therapy has proven to give favorable results after treatment of patients with neuroendocrine tumors. Much focus has been on the binding and uptake of (177)Lu-octreotate in tumor tissue, but biodistribution properties in normal tissues is still not fully understood, and the effect of receptor saturation may be important. The aim of this study was to investigate the influence of the amount of (177)Lu-octreotate on the biodistribution of (177)Lu-octreotate in normal tissues in mice. MATERIAL AND METHODS: C57BL/6N female mice were intravenously injected with 0.1-150 MBq (177)Lu-octreotate (0.039 μg peptide/MBq). The mice were killed 0.25 h to 14 days after injection by cardiac puncture under anesthesia. Activity concentration was determined in blood, bone marrow, kidneys, liver, lungs, pancreas, and spleen, and mean absorbed doses were calculated. RESULTS: The activity concentration varied with time and amount of injected activity. At 4-8 h after injection, a local maximum in activity concentration was found for liver, lungs, pancreas, and spleen. With the exception for the lower injected activities (0.1-1 MBq), the overall highest uptake was found in the kidneys (%IA/g). Large variations were found and the activity concentration in kidneys was 11-23%IA/g at 4 h, and 0.22-1.9%IA/g at 7 days after injection. Furthermore, a clear reduction in activity concentration with increased injected activity was observed for lungs, pancreas and spleen. CONCLUSION: The activity concentration in all tissues investigated was strongly influenced by the amount of (177)Lu-octreotate injected. Large differences in mean absorbed dose per unit injected activity were found between low (0.1-1 MBq, 0.0039-0.039 μg) and moderate amounts (5-45 MBq, 0.2-1.8 μg). Furthermore, the results clearly showed the need for better ways to estimate absorbed dose to bone marrow other than methods based on a single blood sample analysis. Since the absorbed dose to critical organs will limit the amount of (177)Lu-octreotate administered, these findings must be taken into consideration when optimizing this type of therapy.
Authors: Charlotte K Andersson; Emman Shubbar; Emil Schüler; Bo Åkerström; Magnus Gram; Eva B Forssell-Aronsson Journal: J Nucl Med Date: 2019-03-29 Impact factor: 10.057
Authors: Emil Schüler; Maria Larsson; Toshima Z Parris; Martin E Johansson; Khalil Helou; Eva Forssell-Aronsson Journal: PLoS One Date: 2015-08-19 Impact factor: 3.240
Authors: Peter Kletting; Christiane Schuchardt; Harshad R Kulkarni; Mostafa Shahinfar; Aviral Singh; Gerhard Glatting; Richard P Baum; Ambros J Beer Journal: PLoS One Date: 2016-09-09 Impact factor: 3.240