Reactor produced [64Cu]CuCl2 as a PET radiopharmaceutical for cancer imaging: from radiochemistry laboratory to nuclear medicine clinic.

Objective: Copper-64 is a useful theranostic radioisotope that is attracting renewed interest from the nuclear medicine community in the recent times. This study aims to demonstrate the utility of research reactors to produce clinical-grade ⁶⁴Cu via ⁶³Cu(n,γ)⁶⁴Cu reaction and use it in the form of [⁶⁴Cu]CuCl₂ as a radiopharmaceutical for PET imaging of cancer in human patients. Methods: Copper-64 was produced by irradiation of natural CuO target in a medium flux research reactor. The irradiated target was radiochemically processed and detailed quality control analyses were carried out. Sub-acute toxicity studies were carried out with different doses of Cu in Wistar rats. The biological efficacy of the radiopharmaceutical was established in preclinical setting by biodistribution studies in melanoma tumor bearing mice. After getting regulatory approvals, [⁶⁴Cu]CuCl₂ formulation was clinically used for PET imaging of prostate cancer and glioblastoma patients. Results: Large-scale (~ 30 GBq) production of ⁶⁴Cu could be achieved in a typical batch and it was adequate for formulation of clinical doses for multiple patients. The radiopharmaceutical met all the purity requirements for administration in human subjects. Studies carried out in animal model showed that the toxicity due to "cold" Cu in clinical dose of [⁶⁴Cu]CuCl₂ for PET scans would be negligible. Clinical PET scans showed satisfactory uptake of the radiopharmaceutical in the primary cancer and its metastatic sites. Conclusions: To the best of our knowledge, this is the first study on use of reactor produced [⁶⁴Cu]CuCl₂ for PET imaging of cancer in human patients. It is envisaged that this route of production of ⁶⁴Cu would aid towards affordable availability of this radioisotope for widespread clinical use in countries with limited cyclotron facilities. [ABSTRACT FROM AUTHOR]