Reactor produced [ 64 Cu]CuCl 2 as a PET radiopharmaceutical for cancer imaging: from radiochemistry laboratory to nucle
- PDF / 1,472,245 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 115 Downloads / 148 Views
ORIGINAL ARTICLE
Reactor produced [64Cu]CuCl2 as a PET radiopharmaceutical for cancer imaging: from radiochemistry laboratory to nuclear medicine clinic Rubel Chakravarty1,4 · Priyalata Shetty1 · K. V. Vimalnath Nair1 · Ardhi Rajeswari1 · K. C. Jagadeesan1 · Haladhar Dev Sarma2 · Venkatesh Rangarajan3 · Rahul Krishnatry3 · Sudipta Chakraborty1,4 Received: 11 June 2020 / Accepted: 7 September 2020 © The Japanese Society of Nuclear Medicine 2020
Abstract 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 63 Cu(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. Keywords [64Cu]CuCl2 · Glioblastoma · Low specific activity · (n, γ) reaction · PET · Prostate cancer · Theranostics
Introduction
* Rubel Chakravarty [email protected]; [email protected] * Sudipta Chakraborty [email protected] 1
Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India
2
Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India
3
Tata Memorial Centre, Parel, Mumbai 400012, India
4
Homi Bhabha National Institute, Anushaktinagar, Mumbai 400094, India
In the arena of nuclear oncology, the concept of “theranostics” is relatively young but is growing more and more astute at a remarkably fast pace. In fact, the new generation
Data Loading...
