In Vivo Imaging of [60]Fullerene-Based Molecular Spherical Nucleic Acids by Positron Emission Tomography

Abstract

<p>¹⁸F-Labeled [60]fullerene-based molecular spherical nucleic acids (MSNAs), consisting of a human epidermal growth factorreceptor 2 (HER2) mRNA antisense oligonucleotide sequence with a nativephosphodiester and phosphorothioate backbone, were synthesized, site-specificallylabeled with a positron emitting fluorine-18 and intravenously administratedvia tail vein to HER2 expressing HCC1954 tumor-bearing mice. The biodistributionof the MSNAs was monitored in vivo by positron emissiontomography/computed tomography (PET/CT) imaging. MSNA with a nativephosphodiester backbone (MSNA-PO) was prone to rapid nuclease-mediateddegradation, whereas the corresponding phosphorothioate analogue (MSNA-PS)with improved enzymatic stability showed an interesting biodistributionprofile <i>in vivo</i>. One hour after the injection, majorityof the radioactivity was observed in spleen and liver but also inblood with an average tumor-to-muscle ratio of 2. The prolonged radioactivityin blood circulation may open possibilities to the targeted delivery of the MSNAs.</p>