Matthias Miederer et al., EJNMMI Research, 2021
There has been increased interest in the development of mRNA-based vaccines for protection against various infectious diseases and also for cancer immunotherapies since lipid-based nanoparticles opened the possibility to deliver RNA to specific sites within the body, overcoming the limitation of rapid degradation in the bloodstream. In the present study, RNA-lipoplex nanoparticles were assembled by complexing sodium-iodide-symporter (NIS) coding mRNA with liposomes at different charge ratios. Two kinds of RNA-lipoplex systems were used: one system with net anionic charge mediating translation primarily within the spleen, and the other with net positive charge yielding translation primarily within the lungs. After in vitro analysis of the expression kinetics, mice were iv. injected with the mRNA-lipoplexes then 6h later with 124Iodine. Functional NIS protein translation was investigated by PET/MRI imaging. Results revealed rapid increase of 124Iodine uptake in the spleen or lung compared to control-RNA-lipoplexes (containing non-coding RNA) with minimal background in other organs except from thyroid, stomach and salivary gland (where NIS is physiologically expressed). 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.
Results from nanoScan PET/MRI
Female BALB/c mice were intravenously injected with RNA-lipoplexes containing 20μg NIS RNA. Six hours later 6.64±0.66MBq 124Iodine was injected intravenously. Three hours after 124Iodine injection, mice were anesthetized and static imaging was performed over 20min by nanoScan PET/MRI. Additionally, one animal per group was imaged dynamically for one hour.
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