Zr-89-, Y-90- and Lu-177-labeling and biological testing of mesoporous silica based nanoparticles

1064 Objectives Mesoporous silica nanoparticles (MSNs) provide several useful properties for biological applications (e.g. „drug delivery vehicles“ or imaging agents for PET). Compared to non-porous nanoparticles, MSNs have a much higher specific surface area, which can be used for conjugation of chelators and biologically active compounds. Furthermore, the surface can be functionalized with PEG, stabilizing the dispersion and improving blood kinetics. Because of their relatively slow target accumulation it is beneficial to use radionuclides with a long half-life. Our goal was the conjugation of MSNs with different chelators to allow radiolabeling with different radionuclides as Zr-89, Y-90 and Lu-177 as well as the introduction of PEG5000 and subsequently biological evaluation of the labeled MSNs. Methods MSNs (diameter: 200 nm; specific surface area: 275 m2/g) were functionalized with aminopropyl units which served as anchoring points for different chelators ((DFO, DTPA and DTPA-CHX). To improve blood mobility the MSN were additionally covalently modified with PEG5000. The RCY of the Zr-89-, Y-90- and Lu-177-labeling was optimized regarding amount of MSN and reaction time at room temperature in a MSN suspension (10-100 µg, 1 ml 0.25 M HEPES buffer of pH 7.7). In case of the Zr-89-labeled DFO-MSN-PEG and DFO-MSN, the MSN were preclinically evaluated by PET studies in mice. Results The use of small amounts (10µg) of MSN for labeling with Zr-89, Y-90 and Lu-177 led to high RCY >90% within 15 min. For PEGylated MSNs an increased uptake in LNCaP C4-2 tumors compared to nonPEGylated MSNs (2.72 ± 0.86 %ID/g to 0.23 ± 0.12 %ID/g) was observed 60 min post injection. Conclusions An efficient labeling method for chelator-conjugated MSNs under mild reaction conditions in a short reaction time was developed leading to high RCY9s. Moreover, first in vivo experiments showed promising results.