Entwicklung Radiometall-markierter Somatostatin-Analoga Internalisierungsversuche mit DOTA-β-Ala-TOC an der Hamsterglucagonomzelllinie INR1-G9

Eine große Anzahl neuroendokrin aktiver Tumoren besitzen Somatostatin-Rezeptoren, an die radioaktiv markierte Somatostatin-Analoga binden. Primärtumoren und ihre Metastasen können somit, abhängig vom Tumortyp, durch eine Gamma- Kamera in 80% der Fälle nachgewiesen werden. Die oft weniger als 1 cm gr...

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Bibliographic Details
Main Author: Caime, Fabienne
Contributors: Behr, T. M. (Prof. Dr.) (Thesis advisor)
Format: Dissertation
Language:German
Published: Philipps-Universität Marburg 2010
Klinik für Strahlentherapie
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Table of Contents: Neuroendocrine tumours (NETs) represent a heterogeneous family of neoplasms, which may develop from different endocrine glands (such as the pituitary, the parathyroid or the neuroendocrine adrenal glands), endocrine islets (within the thyroid or pancreas) as well as from endocrine cells dispersed between exocrine cells throughout the digestive and respiratory tracts. The development of somatostatin analogues as important diagnostic and treatment tools has revolutionised the clinical management of patients with NETs. However, although symptomatic relief and stabilisation of tumour growth for various periods of time are observed in many patients treated with somatostatin analogues, tumour regression is rare. Primary tumours and her metastases can be proved therefore, depending on the tumour type, by a gamma camera in 80% of the cases. The often less than 1cm tumours are only difficult by other detecting procedures (CT, MRT, endoscopy and sonography). The somatostatinreceptor-Szintigraphy is therefore of any other Staging method with NETs of the gastro-intestinal tract apart from the insulin omen consider. The therapeutic use of somatostatin analogues with patients with NETs takes an increasingly more important position in the nuclear medicine, because these tumours respond only a little to a chemotherapy. It were carried out internalization attempts as well as analysis of externalization. The aim of the attempts was which to compare marked somatostatin analogue DOTA-ß-Ala-TOC to two known peptides radiometal which shows a high affinity to the receptor (in this case somatostatin receptor 2) and a low unspecific connection in the cell membrane. Because with DOTA-ß-Ala-TOC an alanin group has been inserted to increase the distance between Chelator and receptor connection place the receptor affinity increases therefore. Also should be bigger the endozytosis of the peptids (internalization) than of the already used Octreoscans®. Against it the rate in externalizated radiopeptid should be lower, than of the established Octreoscans®. DOTA-ß-Ala-TOC is internalized to a higher portion in the INR1-G9 cells (hamster glucagonoma cells) than DOTATOC and Octreoscan®. And DOTATOC is internalized to a bigger portion than the customary Octreoscan®. The analysis of externalization precipitates with DOTA-ß-Ala-TOC more slightly than with Octreoscan®. Also the portion of the unspecific connection in the cell membrane lies with DOTA-ß-Ala-TOC lower than with Octreoscan®. In the carried out attempts has been shown that in vitro DOTA-ß-Ala-TOC to the customary Octreoscan® consider is. DOTA-ß-Ala-TOC shows a higher internalization rate than DOTATOC in the INR1-G9 cells. It seems to concern with DOTA-ß-Ala-TOC a substance which is suitable to diagnostics and therapy similarly well like DOTATOC. Therefore it can have a meaning for diagnostics and therapy of NETs. Because it itself with the therapy mostly around advanced inoperable tumours acts the side effects are beside the effectiveness the radiotherapeutic of the biggest meaning.