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 99mTc intrinsically labeled ultrasmall magnetic iron oxide nanoparticles with zwitterionic surface coating (99mTc-ZW-USIONPs) via one pot synthesis using sulfobetains functionalized poly (acrylic acid) as stabilizer and Na99mTcO4 and SnCl2 as additives. The commercialization of single photon emission computed tomography (SPECT)/magnetic resonance imaging (MRI) scanner made the combination use of 99mTc 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 99mTc into IONPs, especially those ultrasmall ones without precipitation. We proved that it is possible to prepare 99mTc 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 99mTc-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 99mTc-ZW-USIONPs represent a type of promising dual contrast agent for SPECT/T1 MRI.