64CuCl2 produced by direct neutron activation route as a cost-effective probe for cancer imaging: the journey has begun

Abstract

Copper-64 (t_½ = 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, γ) 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 post-injection, 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.