Original Article

positron emission tomography; titanium-45; intrinsic radiolabeling; mesoporous silica nanoparticle; tumor targeting; 4T1 murine breast tumor

Authors: Feng CHEN, Hector F VALDOVINOS, Reinier HERNANDEZ, Shreya GOEL, Todd E BARNHART, Weibo CAI

Abstract

Titanium-45 (45Ti) with a three-hour half-life (t1/2=3.08 h), low maximum positron energy and high positron emission branching ratio, is a suitable positron emission tomography (PET) isotope whose potential has not yet been fully explored. Complicated radiochemistry and rapid hydrolysis continue to be major challenges to the development of 45Ti compounds based on a traditional chelator-based radiolabeling strategy. In this study we introduced an intrinsic (or chelator-free) radiolabeling technique for the successful labeling of 45Ti using mesoporous silica nanoparticle (MSN). We synthesized uniform MSN with an average particle size of ~150 nm in diameter. The intrinsic 45Ti-labeling was accomplished through strong interactions between 45Ti (hard Lewis acid) and hard oxygen donors (hard Lewis bases), the deprotonated silanol groups (-Si-O-) from the outer surface and inner meso-channels of MSN. In vivo tumor-targeted PET imaging of as-developed PEGylated [45Ti]MSN was further demonstrated in the 4T1 murine breast tumor-bearing mice. This MSNbased intrinsic radiolabeling strategy could open up new possibilities and speed up the biomedical applications of 45Ti in the future.