Diagnostic versus therapeutic doses of [177Lu-DOTA-Tyr 3]-octreotate: Uptake and dosimetry in somatostatin receptor-positive tumors and normal organs
Cancer Biotherapy and Radiopharmaceuticals , Volume 22 - Issue 1 p. 151- 159
Aim: The aim of this study was to investigate the influence of a diagnostic versus therapeutic dose of [177Lu-DOTA-Tyr3]octreotate on the uptake, effects, and dosimetry in somatostatin receptor subtype 2 (sst2)-positive tumors and normal organs in a rat tumor model. Materials and Methods: Lewis rats bearing rat pancreatic CA20948-tumor grafts were injected intravenously with different amounts of radioactivity and peptide of [ 177Lu-DOTA-Tyr3]octreotate: 3 MBq/0.5 μg (group A), 3 MBq/15 μg (group B), 300 MBq/15 μg (group C), and 555 MBq/15 μg (group D). Biodistribution studies were performed at several time points between 3 and 13 days post injection. Ex vivo and in vitro autoradiography was performed with frozen tumor sections. Results: Normal sst2-positive tissues showed a significantly higher uptake of radioactivity [%IA/g] when a low peptide amount was injected. On the other hand, the radioactivity concentration [%IA/g] in sst2-negative tissues and organs (blood, muscles, kidney, and liver) were comparable (groups A and B), independent of the injected peptide amount. Initially, this held true for the tumors as well. Yet, over time, we found a decrease in the radioactivity concentration in the tumors of groups A and B, because of tumor growth. On the other hand, therapeutic amounts of radioactivity (groups C and D) resulted in a significant reduction of tumor size, where radioactivity concentration remained higher than in groups A and B, despite the use of the high peptide amounts. Ex vivo autoradiograms of tumor sections confirmed these results. In vitro autoradiography performed on adjacent tumor sections revealed a reduced density of sst2 in tumors from animals that received a therapeutic radioactivity dose. Ki67-antibody immunohistochemistry showed an absence of proliferating tumor cells after therapy. Conclusions: The differences in radioactivity retention in tumors after diagnostic or therapeutic doses, depending on a change in tumor kinetics, have to be taken into account when calculating tumor-absorbed radiation doses.
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|Cancer Biotherapy and Radiopharmaceuticals|
|Organisation||Department of Nuclear Medicine|
Müller, C, Forrer, F, Bernard, B.F, Melis, M.L, Konijnenberg, M, Krenning, E.P, & de Jong, M. (2007). Diagnostic versus therapeutic doses of [177Lu-DOTA-Tyr 3]-octreotate: Uptake and dosimetry in somatostatin receptor-positive tumors and normal organs. In Cancer Biotherapy and Radiopharmaceuticals (Vol. 22, pp. 151–159). doi:10.1089/cbr.2007.309