Cation exchange reaction in Bi2S3 nanorods enables the one-step fabrication of copper-64 nanoparticulate molecular PET imaging agents with ultrahigh radiolabel stability

Abstract

New molecular positron emission tomography (PET) imaging agents with high radiolabel stability are needed to expand the use of modality in oncology. Due to the radioactive decay of radiometals suitable for PET imaging, the development of a rapid, efficient, and reproducible method is also critical. We present here a novel “shake and use” approach for the production of copper-64 (⁶⁴Cu) nanoparticle-based PET imaging agents based on a cation exchange reaction in metal chalcogenides. ⁶⁴Cu:bismuth sulfide (⁶⁴Cu:Bi₂S₃) nanorods could be prepared within 10 min and under ambient conditions, with an extremely high radiochemical yield of almost 100% and an outstanding radiolabel stability of 99% at 24 h in serum at 37 °C. Remarkably, the ⁶⁴Cu cation exchange reaction can be performed with Cetuximab-functionalized Bi₂S₃ nanorods without impacting the binding performance. The simplicity of the method and excellent radiolabeling and radiolabel stability afforded by the cation exchange reaction of ⁶⁴Cu in Bi₂S₃ suggest the feasibility of “point-of-need” radiolabeling and warrant further investigation.