Synthesis and characterization of intrinsically radiolabeled quantum dots for bimodal detection.

A novel approach was developed to synthesize radioactive quantum dots (r-QDs) thereby enabling both optical and radionuclide signals to be detected from the same intrinsic bimodal probe. This proof-of-concept is exemplified by the incorporation of the radionuclide (109)Cadmium into the core/shell of the nanoparticle. Green and near infrared (NIR) emission intrinsic r-QDs were synthesized and characterized. Zwitterionic and Poly-polyethlene glycol (PEGylated) ligands were synthesized and used to coat r-QDs. Zwitterionic NIR r-QDs (quantum yield = 11%) and PEGylated NIR r-QDs (quantum yield = 14%) with an average size of 13.8 nm and 16.8 nm were obtained respectively. The biodistribution of NIR zwitterionic and PEGylated r-QDs in nude mice was investigated and zwitterionic r-QDs showed longer blood circulation (t(1/2) = 21.4±1.1 hrs) than their PEGylated counterparts (t(1/2) = 6.4±0.5 min). Both zwitterionic and PEGylated r-QDs exhibited progressive accumulation in the liver and spleen, but the magnitude of the accumulation (%ID/g) was about 3-6 fold higher with the PEGylated r-QDs at all the time points. The results demonstrated the feasibility of r-QDs synthesis in quantitative yield and retention of fluorescence following incorporation of radioactivity into the core/shell of the nanoparticle. The gamma signal from the same fluorescent elemental material enabled quantitative and robust pharmacokinetic measurements and how these changed depended on the type of coating ligands used. This strategy for intrinsically radio-labeling the QDs is currently being implemented in our laboratory for the incorporation of other radiometals.