A novel, chelator-free method for 64Cu labeling of dendrimers

Nanoparticles (NPs) have been widely used in biomedical research, but the difficulty in determining their in vivo characteristics limits their clinical translation. So far, positron emission tomography (PET), which requires that the NPs are labeled with an appropriate positron nuclide, appears to be the most likely solution to this problem. Cu-64 is the most frequently used positron emitter in NP research and Cu-64 radiolabeling using chelators is the most commonly used strategy, although this method has some shortcomings in practice. In the present study, we directly integrated Cu-64 into the internal cavities of generation 5 polyamidoamine (G5 PAMAM), a commercially available NP, without the need for chelators. The labeling time, pH level, temperature, and amount of precursor were systematically varied to determine the optimum labeling conditions. Preliminary biological evaluation in mice revealed that the Cu-64 direct labeling method was feasible for the preparation of labeled PAMAM for in vivo studies. This study introduced a novel idea for Cu-64 labeling of dendrimers (and other NPs with a similar structure) and should facilitate the application of NPs in biomedical studies.