Intrinsically copper-64-labeled organic nanoparticles as radiotracers

Nanotechnology has the potential to greatly expand the clinical armamentarium for diagnosing and treating disease. On the road to translating this promise into reality, "one of the top priorities is the determination of the distribution of nanoparticulate carriers in the body following systemic administration through any route". Currently, the only technique that provides quantitative information about the whole body is radiolabeling, for which there are a number of approaches, as illustrated in Figure 1: A) the radionuclide is attached to the nanoparticle surface by an exogenous chelator; B) the radionuclide is entrapped in an enclosed compartment, or C) nanoparticles are manufactured from pre-radiolabeled building blocks. Each method suffers from some combination of the following limitations: in vivo instability and/or low specific activity (activity per unit mass) of the radiolabeled nanoparticle, or restrictive radiolabeling procedures with low radiochemical yields, long and complicated procedures, and narrow concentration ranges of the labeling. Furthermore, the in vivo instability of exogenous chelators and entrapped radionuclides leads to concerns that the label is not faithful to the nanostructure or alters it such that the in vivo behavior of the radiolabeled nanoparticle differs from that of the same parent nanoparticles without the radiolabel. By using prelabeled building blocks some of these concerns can be avoided, but the burden of manufacturing the nanoparticles is transferred to the end user. Therefore, the ideal approach would allow preformed nanoparticles to be labeled stably without affecting their in vivo behavior.