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Authors: Miederer, Matthias
Pektor, Stefanie
Miederer, Isabelle
Bausbacher, Nicole
Keil, Isabell Sofia
Hefesha, Hossam
Haas, Heinrich
Sahin, Ugur
Diken, Mustafa
Title: Iodine-124 PET quantifcation of organ-specifc delivery and expression of NIS-encoding RNA
Online publication date: 17-Aug-2021
Language: english
Abstract: BACKGROUND: RNA-based vaccination strategies tailoring immune response to specifc reactions have become an important pillar for a broad range of applications. Recently, the use of lipid-based nanoparticles opened the pos sibility to deliver RNA to specifc sites within the body, overcoming the limitation of rapid degradation in the blood stream. Here, we have investigated whether small animal PET/MRI can be employed to image the biodistribution of RNA-encoded protein. For this purpose, a reporter RNA coding for the sodium-iodide-symporter (NIS) was in vitro transcribed in cell lines and evaluated for expression. RNA-lipoplex nanoparticles were then assembled by complex ing RNA with liposomes at diferent charge ratios, and functional NIS protein translation was imaged and quantifed in vivo and ex vivo by Iodine-124 PET upon intravenous administration in mice. RESULTS: NIS expression was detected on the membrane of two cell lines as early as 6 h after transfection and gradu ally decreased over 48 h. In vivo and ex vivo PET/MRI of anionic spleen-targeting or cationic lung-targeting NIS-RNA lipoplexes revealed a visually detectable rapid increase of Iodine-124 uptake in the spleen or lung compared to control-RNA-lipoplexes, respectively, with minimal background in other organs except from thyroid, stomach and salivary gland. CONCLUSIONS: The strong organ selectivity and high target-to-background acquisition of NIS-RNA lipoplexes indicate the feasibility of small animal PET/MRI to quantify organ-specifc delivery of RNA.
DDC: 610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
Place: Mainz
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC-BY
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Journal: EJNMMI Research
Pages or article number: 14
Publisher: Springer
Publisher place: Berlin u.a.
Issue date: 2021
ISSN: 2191-219X
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Appears in collections:JGU-Publikationen

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