Mechanisms of inclusion of thallium-201 into Prussian blue nanoparticles for nuclear medicine applications

Prussian blue is known for its high affinity for thallium and other univalent metal cations and has been used as a treatment for radiocaesium and thallium/radiothallium poisoning. While Prussian blue nanoparticles (PBNPs) show potential for binding radioactive thallium for further use in nuclear medicine applications, the inclusion mechanism remains elusive. Understanding the interaction between PBNPs and 201 Tl is essential for identifying the physicochemical and radiochemical properties required for optimal in vivo performance. In this work, we evaluated the binding mechanism between Tl and PBNPs with different coatings and core shapes. Combining PBNPs with [ 201 Tl] thallium( i ) chloride provided high radiolabelling yields and radiochemical stabilities under physiological conditions. Comprehensive characterisation by different X-ray techniques confirmed that Tl ions are located in the interstitial sites within the crystal structure, maintaining the integrity of the iron (Fe) 4p electronic distribution and inducing local modifications in the nearby C-N ligands. Additionally, this inclusion does not impact the core or the shell of the nanoparticles but does alter their ionic composition. The PB ionic network undergoes significant changes, with a substantial drop in K + content, confirming that Tl + ions replace K + and occupy additional spaces within the crystal structure. These results open new opportunities in nuclear medicine applications with 201 Tl-PBNPs where the size, shape and composition of the particles can be specifically tuned depending on the desired biological properties without affecting the radiochemical performance as a vehicle for 201 Tl. Prussian blue nanoparticles are radiolabelled with Tl-201 and characterised to provide the unambiguous confirmation of the inclusion mechanism.