Der Natrium-Iodid-Symporter (NIS): Bedeutung für die Bildgebung und therapeutische Optionen

Zusammenfassung

Der Natrium-Iodid-Symporter (NIS) vermittelt als intrinsisches Membranprotein den aktiven Transport von Iodid in die Schilddrüse sowie eine Reihe extrathyreoidaler Organe, insbesondere die laktierende Brustdrüse. Neben seiner Schlüsselrolle in der Schilddrüsenphysiologie bildet NIS die Grundlage der diagnostischen Schilddrüsenszintigrafie sowie der therapeutischen Anwendung von Radioiod bei der Behandlung benigner und maligner Schilddrüsenerkrankungen, und stellt damit eines der ältesten Targets molekularer Bildgebung und Therapie dar. In Anlehnung an die seit mehr als 60 Jahren mit großem Erfolg beim Schilddrüsenkarzinom eingesetzten Radioiodtherapie, ermöglicht die Klonierung und Charakterisierung des NIS-Gens die Entwicklung eines neuen, zytoreduktiven Gentherapieansatzes auf dem Boden der gezielten NIS-Expression in thyreoidalen und extrathyreoidalen Tumoren gefolgt von der therapeutischen Applikation von ¹³¹I oder alternativer Radionuklide, wie ¹⁸⁸Re oder ²¹¹At. Darüber hinaus erlaubt die Möglichkeit des direkten, nicht-invasiven Imagings funktioneller NIS-Expression mittels ¹²³I- und ^99mTc-Szintigrafie oder ¹²⁴I-PET-Imaging den Einsatz von NIS als neuem Reportergen. Zusammenfassend eröffnet die Doppelfunktion von NIS als diagnostisches und therapeutisches Gen sowie der Nachweis extrathyreoidaler endogener NIS-Expression in Mammakarzinomen viel versprechende Perspektiven in der Nuklearmedizin und molekularen Onkologie für die diagnostische und therapeutische Applikation von NIS auch außerhalb der Schilddrüse.

Abstract

The sodium iodide symporter (NIS) is an intrinsic plasma membrane glycoprotein that mediates the active transport of iodide in the thyroid gland and a number of extrathyroidal tissues, in particular lactating mammary gland. In addition to its key function in thyroid physiology, NIS-mediated iodide accumulation allows diagnostic thyroid scintigraphy as well as therapeutic radioiodine application in benign and malignant thyroid disease. NIS therefore represents one of the oldest targets for molecular imaging and therapy. Based on the effective administration of radioiodine that has been used for over 60 years in the management of follicular cell-derived thyroid cancer, cloning and characterization of the NIS gene has paved the way for the development of a novel cytoreductive gene therapy strategy based on targeted NIS expression in thyroidal and nonthyroidal cancer cells followed by therapeutic application of ¹³¹I or alternative radionuclides, including ¹⁸⁸Re and ²¹¹At. In addition, the possibility of direct and non-invasive imaging of functional NIS expression by ¹²³I- and ^99mTc-scintigraphy or ¹²⁴I-PET-imaging allows the application of NIS as a novel reporter gene. In conclusion, the dual role of NIS as diagnostic and therapeutic gene and the detection of extrathyroidal endogenous NIS expression in breast cancer open promising perspectives in nuclear medicine and molecular oncology for diagnostic and therapeutic application of NIS outside the thyroid gland.

Natrium-Iodid-Symporter - Radioiodtherapie - molekulare Bildgebung - molekulare Therapie - NIS-Gentherapie - NIS-Reportergen - Mammakarzinom - Radionuklidtherapie

sodium iodide symporter (NIS) - radioiodine therapy - molecular imaging - molecular therapy - NIS gene therapy - NIS reporter gene - mammary cancer - radionuclide therapy

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