Synthesis of intrinsically radiolabeled nanoparticles is an emerging concept in cancer theranostics and is expected to play an imperative role in translating nanotechnology research into the nuclear medicine industry. In order to reduce reliance on cyclotron produced Cu-64 (t(1/2) = 12.7 h, EC 45%, beta(+) 17.9%, beta(-) 37.1%) and increase global accessibility of this radioisotope for preclinical and clinical investigations, we have explored the feasibility of using neutron-activated Cu-64 produced in research reactors for potential use in cancer theranostics. A viable strategy has been developed for production of Cu-64 in medium-flux research reactors and its utilization toward industrial-scale (GBq level) synthesis of intrinsically radiolabeled (CuS)-Cu-64 nanoparticles (similar to 30 nm particle size). The synthesis procedure was easily executable in a hot cell equipped with remotely operable gadgets and (CuS)-Cu-64 nanoparticles could be synthesized in a form suitable for clinical administration. The stability of the nanoparticles under physiological conditions was established by detailed in vitro studies in phosphate buffered saline (PBS) and mouse serum media. The biological efficacy of intrinsically radiolabeled (CuS)-Cu-64 nanoparticles was studied in C57BL/6 mice bearing melanoma tumors. The results of the biodistribution studies revealed significant tumor uptake (4.64% +/- 1.71%ID/g) within 4 h post-injection (where %ID is the percent injected radioactivity dose), with good tumor-to-background contrast. Collectively, the promising results obtained in this study suggest that the concept of intrinsically radiolabeled nanoplatforms can be employed to facilitate widespread utilization of neutron-activated Cu-64 in nuclear medicine industry.