Intrinsic radiolabeling of Titanium-45 using mesoporous silica nanoparticles

Titanium-45 (⁴⁵Ti) with a three-hour half-life (t_1/2=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 MSN-based intrinsic radiolabeling strategy could open up new possibilities and speed up the biomedical applications of ⁴⁵Ti in the future.