Gentechnisch modulierte Iodidanreicherung in malignen Tumoren

Summary

After the cloning of the gene encoding the sodium-iodide symporter several trials were made to develop a radioiodine treatment for multiple tumour entities based on NIS gene transfer. These studies revealed in vitro as well as in vivo a tremendous enhancement of iodide accumulation, which was followed by a rapid efflux. Therapy effects were observed in vitro by clonogenic assays and in vivo by growth inhibition of the treated tumours. However, the interpretation of these results were largely different. Problems of radioiodine therapy after NIS transfer are low efficiency of gene transfer and the short exposure time for the tumours caused by the rapid efflux. Trials to enhance therapeutic efficiency by co-transfer of the gene encoding thyroperoxidase failed due to the low enzyme activity.

Zusammenfassung

Die Klonierung des Gens für den Natrium-Iodid-Symporter führte zu Versuchen, mittels Transfer dieses Gens eine biotechnologisch unterstützte Radioiodtherapie bei einer Vielzahl von Tumoren zu erreichen. Diese ergaben in vitro und in vivo eine stark erhöhte Iodidanreicherung, die jedoch von einem schnellen Efflux gefolgt war. Therapieeffekte wurden in vitro mittels klonogenen Assays und in vivo über eine Hemmung des Tumorwachstums beobachtet. Bezüglich der Interpretation dieser Ergebnisse bestehen divergierende Ansichten. Probleme der Radioiodtherapie nach NIS-Transfer sind sicherlich die mangelhafte Effizienz des Gentransfers und die durch den schnellen Efflux kurze Expositionsdauer der Tumoren. Versuche, die Therapieeffizienz durch Kotransfer des Gens für die Schilddrüsenperoxidase zu steigern, scheiterten bisher an der geringen Enzymaktivität.

Keywords

Gene transfer - sodium iodide symporter - thyroid peroxidase - tumour - therapy

Schlüsselwörter

Gentransfer - Natrium-Iodid-Symporter - Schilddrüsenperoxidase - Tumor - Therapie

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