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.[3]
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.[4][5][6]
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.[10]
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 allergeniccontrast 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.[11][12]
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.[13]
Cancer therapy
64Cu-ATSM – copper(II) (diacetyl-bis (N4-methylthiosemicarbazone)) – is being studied as a possible 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.[14]
^Parry, Jesse J.; Andrews, Rebecca; Rogers, Buck E. (13 July 2006). "MicroPET Imaging of Breast Cancer Using Radiolabeled Bombesin Analogs Targeting the Gastrin-releasing Peptide Receptor". Breast Cancer Research and Treatment. 101 (2): 175–183. doi:10.1007/s10549-006-9287-8. PMID16838112. S2CID25579379.
^Green, Mark A.; Mathias, Carla J.; Willis, Lynn R.; Handa, Rajash K.; Lacy, Jeffrey L.; Miller, Michael A.; Hutchins, Gary D. (April 2007). "Assessment of Cu-ETS2 as a PET radiopharmaceutical for evaluation of regional renal perfusion". Nuclear Medicine and Biology. 34 (3): 247–255. doi:10.1016/j.nucmedbio.2007.01.002. PMID17383574.
