Optimierung der Lutetium-177 DOTATOC Synthese und Untersuchung des peptidabhängigen Uptakes im Hinblick auf die Peptid-Rezeptor-Radionuklidtherapie von Neuroendokrinen Tumoren im Zellversuch mit AR42J Zellen

In der vorliegenden Arbeit wurde die radiochemische Synthese von Lu-177 DOTATOC optimiert und der veränderte Uptake an AR42J-Zellen durch die geänderte Peptidkonzentration untersucht. Ausgehend von einer Lu-177 DOTATOC-Synthese mit 8 GBq Lu-177, welche 200 μg an DOTATOC verwendet hat und in einem N...

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Bibliographic Details
Main Author: Fellinger, Sebastian Alfons
Contributors: Jungclas, Hartmut (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Language:German
Published: Philipps-Universität Marburg 2018
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Table of Contents: In the present work, the radiochemical synthesis of Lu-177 DOTATOC has been optimized and altered uptake by the modified peptide concentration has been tested at AR42J cells. Starting from a Lu-177 DOTATOC synthesis with 8 GBq Lu-177, which has used 200 μg DOTATOC in a sodium ascorbate / ascorbic acid buffer, the preparation has been optimized, thus from now on only 20 μg peptide are required. Furthermore the synthesis will be carried out in a sodium acetate buffer. In all subsequent syntheses yields of 100% have been achieved. In the experiments, the cell uptake of Lu-177 DOTATOC and Cu-64 DOTATOC to AR42J cells at different peptide concentrations was analyzed. It has been shown, that the uptake depends on the concentration of the peptide used. If less peptide is used for the same activity, the mean uptake increases. This applies both to the test series with Lu-177 DOTATOC, and for the series of experiments with Cu-64 DOTATOC. The uptake behavior resembles the adsorption isotherm of Langmuir. The evaluation of the planar whole body scintigraphies on the Krenning scale showed no differences in the uptake in the kidneys or metastases. However, they also showed no decrease in the uptake, which tenders the synthesis of Lu-177 DOTATOC more cost effective by the lower peptide use.