Controllable synthesis of barium carbonate nano- and microparticles for SPECT and CT imaging

The design and synthesis of nano- and microcarriers for preclinical and clinical imaging are highly attractive due to their unique features, for example, multimodal properties. However, broad translation of these carriers into clinical practice is postponed due to the unknown biological reactivity of the new components used for their synthesis. Here, we have developed microcarriers (∼2-3 μm) and  nanocarriers (<200 nm) made of barium carbonate (BaCO₃) for multiple imaging applications in vivo. In general, barium in the developed carriers can be used for X-ray computed tomography, and the introduction of a diagnostic isotope (^99mTc) into the BaCO₃ structure enables in vivo visualization using single-photon emission computed tomography. The bioimaging has shown that the radiolabeled BaCO₃ nano- and microcarriers had different biodistribution profiles and tumor accumulation efficiencies after intratumoral and intravenous injections. In particular, in the case of intratumoral injection, all the types of used carriers mostly remained in the tumors (>97%). For intravenous injection, BaCO₃ microcarriers were mainly localized in the lung tissues. However, BaCO₃ NPs were mainly accumulated in the liver. These results were supported by ex vivo fluorescence imaging, direct radiometry, and histological analysis. The BaCO₃-based micro- and nanocarriers showed negligible in vivo toxicity towards major organs such as the heart, lungs, liver, kidneys, and spleen. This study provides a simple strategy for the design and fabrication of the BaCO₃-based carriers for the development of dual bioimaging.