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

• Published in: Annals of nuclear medicine 2020-12, Vol.34 (12), p.899-910
• Main Authors: Chakravarty, Rubel, Shetty, Priyalata, Nair, K. V. Vimalnath, Rajeswari, Ardhi, Jagadeesan, K. C., Sarma, Haladhar Dev, Rangarajan, Venkatesh, Krishnatry, Rahul, Chakraborty, Sudipta
• Format: Article
• Language: English
• Subjects: Imaging; Medicine; Medicine & Public Health; Nuclear Medicine; Original Article; Radiology
• ISSN: 0914-7187; 1864-6433
• DOI: 10.1007/s12149-020-01522-2

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 64 Cu via 63 Cu(n,γ) 64 Cu reaction and use it in the form of [ 64 Cu]CuCl 2 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, [ 64 Cu]CuCl 2 formulation was clinically used for PET imaging of prostate cancer and glioblastoma patients. Results Large-scale (~ 30 GBq) production of 64 Cu 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 [ 64 Cu]CuCl 2 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 [ 64 Cu]CuCl 2 for PET imaging of cancer in human patients. It is envisaged that this route of production of 64 Cu would aid towards affordable availability of this radioisotope for widespread clinical use in countries with limited cyclotron facilities.