In vivo tracking of plasmid DNA/mRNA: A novel labelling precursor for ⁸⁹Zr positron emission tomography

Area of Science:

• Biomedical imaging
• Molecular biology
• Radiochemistry

Background:

• Plasmid DNA (pDNA) is crucial for gene therapy and research.
• Non-invasive imaging of pDNA delivery is essential for therapeutic development.
• Current labeling methods for pDNA may affect its biological activity.

Purpose of the Study:

• To develop a novel labeling precursor for ⁸⁹Zr-based PET imaging of pDNA.
• To evaluate the gene expression and biodistribution of ⁸⁹Zr-labeled pDNA.
• To assess the applicability of this labeling method to mRNA.

Main Methods:

• Synthesis of a novel labeling precursor, Fe-DFO-5.
• Radiolabeling of plasmid DNA (pDNA) with ⁸⁹Zr.
• In vitro gene expression assays.
• In vivo biodistribution studies in mice.
• Application of the labeling method to mRNA.

Main Results:

• Successful development of the Fe-DFO-5 precursor for ⁸⁹Zr labeling.
• ⁸⁹Zr-labeled pDNA demonstrated comparable gene expression to unlabeled pDNA.
• Biodistribution of ⁸⁹Zr-labeled pDNA was successfully evaluated after local and systemic administration.
• The labeling technique was also effective for mRNA.

Conclusions:

• Fe-DFO-5 is a viable precursor for ⁸⁹Zr labeling of pDNA for PET imaging.
• ⁸⁹Zr-labeled pDNA is suitable for gene expression studies and biodistribution analysis.
• This novel labeling approach holds promise for imaging nucleic acid delivery in vivo, including mRNA.