Iodine-124 PET Quantification of Organ-specific Delivery and Expression of NIS-encoding RNA

Overview

Journal EJNMMI Res

Date 2021 Feb 11

PMID 33569663

Citations 1

Authors

Matthias Miederer

Stefanie Pektor

Isabelle Miederer

Nicole Bausbacher

Isabell Sofia Keil

Hossam Hefesha

Heinrich Haas

Ugur Sahin

Mustafa Diken

Affiliations

Soon will be listed here.

Abstract

Background: RNA-based vaccination strategies tailoring immune response to specific reactions have become an important pillar for a broad range of applications. Recently, the use of lipid-based nanoparticles opened the possibility to deliver RNA to specific sites within the body, overcoming the limitation of rapid degradation in the bloodstream. 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 complexing RNA with liposomes at different charge ratios, and functional NIS protein translation was imaged and quantified 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 gradually 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-specific delivery of RNA.

Citing Articles

Spatiotemporal quantitative microRNA-155 imaging reports immune-mediated changes in a triple-negative breast cancer model.

Skourti E, Volpe A, Lang C, Johnson P, Panagaki F, Fruhwirth G Front Immunol. 2023; 14:1180233.

PMID: 37359535 PMC: 10285160. DOI: 10.3389/fimmu.2023.1180233.

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