Copper-64 (t_1/2 = 12.7 h, E.C. 45%, β^- 37.1%, β⁺ 17.9%) is a promising radionuclide for positron emission tomography (PET) imaging and is generally produced by the ⁶⁴Ni(p, n)⁶⁴Cu nuclear reaction in a cyclotron. Despite the excellent attributes of ⁶⁴Cu for PET imaging, the utility of this radioisotope is still limited to countries having good cyclotron facilities and excellent production logistics. We have explored the feasibility of using ⁶⁴Cu in the form of ⁶⁴CuCl₂, produced in research reactors by an (n, Υ) route, as a probe for tumor imaging by PET. The production strategy has been optimized to obtain ⁶⁴CuCl₂ with adequate specific activity and radionuclidic purity suitable for clinical use. Exploring copper metabolism as an imaging biomarker, ⁶⁴CuCl₂ can directly be used as an effective probe for non-invasive visualization of tumors. The stability of 64CuCl2 under physiological conditions was assessed by detailed in vitro studies in mouse serum medium. The biological efficacy of 64CuCl2 was studied in C57BL/6 mice bearing melanoma tumors and Swiss mice bearing fibrosarcoma tumors. The results of the biodistribution studies revealed significant tumor uptake (7.64 ± 1.71% ID per g in melanoma, 6.54 ± 1.41% ID per g in fibrosarcoma) within 4 h postinjection, with good tumor-to-background contrast. To the best of our knowledge, this is the first study which employs neutron activated ⁶⁴CuCl₂ as a potential radiotracer for PET imaging in preclinical settings. Owing to the availability of several medium-flux nuclear reactors with good geographical distribution in different parts of the world, the promising results obtained in this study would set the stage for wide-scale utilization of neutron activated ⁶⁴CuCl₂ as a cost-effective probe for PET imaging.