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

Abstract

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 ⁸⁹Zr isotope (half-life of 78.4 hours). Here, ⁸⁹Zr⁴⁺ 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 ⁸⁹Zr⁴⁺ labeling was achieved within just a few minutes, and no subsequent purification step was needed in order to remove non-complexed ⁸⁹Zr⁴⁺. The stability of the ⁸⁹Zr-labeled MSNs against leaching of ⁸⁹Zr⁴⁺ was verified for 24 hours. The high signal strength of the ⁸⁹Zr-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 ⁸⁹Zr-DFO-MSNs are promising PET imaging agents for long-term in vivo imaging.