Approach to Chelating Radioactivity using Carbon Dots for Positron Emission Tomography Imaging

With the rapid development of the radiotheranostic field, developing new methods to produce radiolabeled agents has become a critical area of exploration. We hypothesized that the inert carbon shell of carbon dots (CDs) could serve as a robust chelation strategy to overcome the stability issue of radiometal complexes, including the recoil energy issue of alpha (α)-emitting radioisotopes. To investigate this, we utilized radioactive copper-64 (⁶⁴Cu) as a surrogate for therapeutic isotopes and optimized a synthetic route for encapsulating ⁶⁴Cu within CDs (⁶⁴Cu@C). Our findings confirmed that CDs effectively encapsulated ⁶⁴Cu with minimal leakage. Positron emission tomography (PET) imaging of ⁶⁴Cu@C in tumor-bearing rodent models showed a predominant uptake in the liver. To improve tumor targeting, we implemented two strategies: (1) encapsulating ⁶⁴Cu@C within PEGylated liposomes (⁶⁴Cu@C-PEGLipo) as nanocarriers, and (2) preinjecting positively charged liposomes (DOTAPLipo) to block the reticuloendothelial system prior to administering ⁶⁴Cu@C (DOTAPLipo-preinjected-⁶⁴Cu@C). These approaches resulted in 1.7-fold and 2.5-fold increases in tumor uptake, respectively, at 1 h postinjection. In conclusion, these findings highlight the potential of CDs as a stable platform for radiometal encapsulation and demonstrate effective strategies for enhancing tumor-specific delivery in radiotheranostic applications.