Zr-89 labeling of mesoporic silica based nanoparticles

Objectives Mesoporic silica based nanoparticels (MSN) provide versatile perspectives as drug delivery vehicles. In contrast to nonporous silica nanoparticels the MSN have a tremendous increased surface, which can be functionalized and conjugated to multiple residues for targeting and for chelation of radionuclides. This may lead to a clearly improved signal to noise ratio in PET. Also, for a therapeutic application multiple labeling would be of highest interest. Due to slow in vivo accumulation radionuclides with long half-life and sufficient positron percentage are preferred for the PET application. Zr-89 with a half-life of 78,4 h is a well suited positron emitting radionuclide for this purpose. Our goal was the development of a convenient radiolabeling procedure for MSN with Zr-89 for later in vivo experiments.

Methods MSN (size: 200 nm, surface:275 m2/g) were functionalized with propylamino groups which were conjugated in the next step with desferrioxamine. Radiosynthesis of 89Zr-DFO-MSN was developed regarding reaction-time and amount of MSN. Labeling reactions were carried out at room temperature in a MSN suspension (10-100 µg) in 0,1 M NH4OAc buffer of pH 7.7. RCY were determined after 1, 5, 15 and 30 min reaction time. Stability was monitored for 24 h.

Results The functionalization of the MSN was verified by elementary analysis and adsorption measurements. For low concentrations of 10 µg the RCY obtained after 5 min was 67% and increased to a RCY >99% after 15 min. Using higher concentration of the MSN starting from 50 µg a quantitative RCY was obtained after just 1 min. 89Zr-DFO-MSN showed stability over 24h.

Conclusions An efficient method for the labeling of MSN with high surface as a new agent for PET imaging was developed. Quantitative labeling yield were observed already after a reaction time of 15 minutes. Moreover, the ability to label desferal conjugated MSN under mild conditions (room temperature, pH = 7,7) avoids decomposition of the MSN.