Synthesis, characterization, and biodistribution of multiple Zr-89-labeled pore-expanded mesoporous silica nanoparticles for PET

Functional nanoparticles are highly interesting imaging agents for positron emission tomography (PET) due to the possibility of multiple incorporation of positron emitting radionuclides thus increasing the signal strength. Furthermore, long-term nanoparticle biodistribution tests with increased signal-to-noise ratio can be achieved with nanoparticles carrying long-lived isotopes. Mesoporous silica nanoparticles, MSNs, have recently attracted a lot of interest as both imaging agents and carriers for drugs in vitro and in vivo. Here we present results related to the synthesis of PET imageable MSNs carrying the long-lived Zr-89 isotope (half-life of 78.4 hours). Here, Zr-89(4+) was immobilized through covalent attachment of the complexing agent p-isothiocyanatobenzyldesferrioxamine (DFO-NCS) to large-pore MSNs. Due to the presence of the high DFO content on the MSNs, quantitative Zr-89(4+) labeling was achieved within just a few minutes, and no subsequent purification step was needed in order to remove non-complexed Zr-89(4+). The stability of the Zr-89-labeled MSNs against leaching of Zr-89(4+) was verified for 24 hours. The high signal strength of the Zr-89-DFO-MSNs was evidenced by successful PET imaging using a mouse model at particle loadings one order of magnitude lower than those previously applied in PET-MSN studies. The biodistribution followed the same trends as previously observed for MSNs of different sizes and surface functionalities. Taken together, our results suggest that Zr-89-DFO-MSNs are promising PET imaging agents for long-term in vivo imaging.