One pot synthesis of zwitteronic 99mTc doped ultrasmall iron oxide nanoparticles for SPECT/T1-weighted MR dual-modality tumor imaging

In this study, we have synthesized Tc-99m intrinsically labeled ultrasmall magnetic iron oxide nanoparticles with zwitterionic surface coating (Tc-99m-ZW-USIONPs) via one pot synthesis using sulfobetains functionalized poly (acrylic acid) as stabilizer and (NaTcO4)-Tc-99m and SnCl2 as additives. The commercialization of single photon emission computed tomography (SPECT)/magnetic resonance imaging (MRI) scanner made the combination use of Tc-99m and iron oxide nanoparticles attracting much attention. Direct doping radioisotope into nanoparticles has the advantages of excellent radiochemical stability and no restriction on the surface functionalization. The complex Technetium chemistry made it challenging to direct dope Tc-99m into IONPs, especially those ultrasmall ones without precipitation. We proved that it is possible to prepare Tc-99m doped USIONPs with excellent water solubility and favorable T1 signal by controlling the radioactivity and reducing agent amount. With no need of chelator, the zwitterionic surface resists the protein corona formation, resulting in a reduced RES uptake and higher tumor contrast. The Tc-99m-ZW-USIONPs demonstrated excellent performance of tumor SPECT and T1-weighted MR imaging capability in 4T1 tumor bearing mice. Together with their ease of preparation and superior biocompatibility, we believe these Tc-99m-ZW-USIONPs represent a type of promising dual contrast agent for SPECT/T1 MRI.

Automated summary

Successful synthesis of Tc-99m doped USIONPs with excellent water solubility and favorable T1 signal was achieved by controlling the radioactivity and reducing agent amount. The zwitterionic surface coating helps resist protein corona formation, resulting in reduced RES uptake and higher tumor contrast. Tc-99m-ZW-USIONPs showed promising tumor SPECT and T1-weighted MR imaging capabilities in 4T1 tumor bearing mice.