Copper-64

Production

Copper-64 can be produced by several different reactions with the most common methods using either a reactor or a particle accelerator. Thermal neutrons can produce ⁶⁴Cu in low specific activity (the number of decays per second per amount of substance) and low yield through the ⁶³Cu(n,γ)⁶⁴Cu reaction. At the University of Missouri Research Reactor Center (MURR) ⁶⁴Cu was produced using high-energy neutrons via the ⁶⁴Zn(n,p)⁶⁴Cu nuclear reaction in high specific activity but low yield. Using a biomedical cyclotron the ⁶⁴Ni(p,n)⁶⁴Cu nuclear reaction can produce large quantities of the nuclide with high specific activity.

Applications

As a positron emitter, ⁶⁴Cu has been used to produce experimental and clinical radiopharmaceuticals for the imaging of a range of conditions. Its beta emissions also raise the possibility of therapeutic applications. Compared to typical PET radionuclides it has a relatively long half-life, which can be advantageous for therapy, and for imaging certain physiological processes.

PET imaging

Bone metastases

Experimental preclinical work has shown that ⁶⁴Cu linked to methanephosphonate functional groups has potential as a bone imaging agent.

Neuroendocrine tumors (NETs)

Neuroendocrine tumors (NETs) are localised clinically using a range of DOTA based radiopharmaceuticals. For PET imaging these are typically Gallium-68 based. A commercial ⁶⁴Cu-DOTA-TATE product has been FDA approved for localization of somatostatin receptor positive NETs since 2020.

Prostate cancer

The Bombesin peptide has been shown to be overexpressed in BB2 receptors in prostate cancer. CB-TE2A a stable chelation system for ⁶⁴Cu was incorporated with Bombesin analogs for in vitro and in vivo studies of prostate cancer. PET-CT imagining studies showed that it underwent uptake into prostate tumor xenografts selectively with decreased uptake into non target tissues. Other preclinical studies have shown that by targeting the gastrin-releasing peptide receptor pancreatic and breast cancer can also be detected.

Renal perfusion

Ethylglyoxal bis(thiosemicarbazone) (ETS) has potential utility as a PET radiopharmaceutical with the various isotopes of copper. ⁶⁴Cu-ETS has been used for experimental preclinical myocardial, cerebral and tumor perfusion evaluations, with a linear relationship between the renal uptake and blood flow. Renal perfusion can also be evaluated with CT or MRI instead of PET, but with drawbacks: CT requires administration of potentially allergenic contrast agents. MRI avoids use of ionising radiation but is difficult to implement, and often suffers from motion artefacts. PET with ⁶⁴Cu can offer quantitative measurements of renal perfusion.

Wilson’s disease

Wilson disease is a rare condition in which copper is retained excessively in the body. Toxic levels of copper can lead to organ failure and premature death. ⁶⁴Cu has been used experimentally to study whole body retention of copper in subjects with this disease. The technique can also separate heterozygous carriers and homozygous normals.

Cancer therapy

⁶⁴Cu-ATSM (diacetyl-bis(N4-methylthiosemicarbazone)) has been shown to increase the survival time of tumor-bearing animals. Areas of low oxygen retention have been shown to be resistant to external beam radiotherapy because hypoxia reduces the lethal effects of ionizing radiation. ⁶⁴Cu was believed to kill these cells because of its unique decay properties. In animal models having colorectal tumors with and without induced hypoxia, Cu-ATSM was preferentially taken up by hypoxic cells over normoxic cells. The results demonstrated that this compound increased survival of the tumor bearing hamsters compared with controls.