Copper-64 (⁶⁴Cu) is a positron and beta emitting

isotope Isotopes are two or more types of atoms that have the same atomic number (number of protons in their nuclei) and position in the periodic table (and hence belong to the same chemical element), and that differ in nucleon numbers (mass numb ...

copper Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkis ...

, with applications for molecular radiotherapy and positron emission tomography. Its unusually long half-life (12.7-hours) for a positron-emitting isotope makes it increasingly useful when attached to various ligands, for PET and PET-CT scanning.

Properties

⁶⁴Cu has a

half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable at ...

of 12.7 hours and decays 17.9% by

positron emission Positron emission, beta plus decay, or β+ decay is a subtype of radioactive decay called beta decay, in which a proton inside a radionuclide nucleus is converted into a neutron while releasing a positron and an electron neutrino (). Positron ...

to ⁶⁴Ni, 39.0% by

beta decay In nuclear physics, beta decay (β-decay) is a type of radioactive decay in which a beta particle (fast energetic electron or positron) is emitted from an atomic nucleus, transforming the original nuclide to an isobar of that nuclide. For ...

to ⁶⁴Zn, 43.1% by

electron capture Electron capture (K-electron capture, also K-capture, or L-electron capture, L-capture) is a process in which the proton-rich nucleus of an electrically neutral atom absorbs an inner atomic electron, usually from the K or L electron shells. Thi ...

to ⁶⁴Ni, and 0.475% gamma radiation/

internal conversion Internal conversion is a non-radioactive, atomic decay process where an excited nucleus interacts electromagnetically with one of the orbital electrons of an atom. This causes the electron to be emitted (ejected) from the atom. Thus, in internal ...

. These emissions are 0.579

MeV In physics, an electronvolt (symbol eV, also written electron-volt and electron volt) is the measure of an amount of kinetic energy gained by a single electron accelerating from rest through an electric potential difference of one volt in vacu ...

, 0.653 MeV and 1.35 MeV for beta minus, positron, and gamma respectively. The

oxidation state In chemistry, the oxidation state, or oxidation number, is the hypothetical charge of an atom if all of its bonds to different atoms were fully ionic. It describes the degree of oxidation (loss of electrons) of an atom in a chemical compound. C ...

s of

in biology are I and II since Cu³⁺ is too powerful to exist in biochemical systems. Furthermore, copper(I) exists as a strong complex in aqueous solution and is not often seen. Copper(II) forms mononuclear complexes that are

paramagnetic Paramagnetism is a form of magnetism whereby some materials are weakly attracted by an externally applied magnetic field, and form internal, induced magnetic fields in the direction of the applied magnetic field. In contrast with this behavior, ...

and prefers ligands of sulfur and nitrogen. Copper is essential in the human body as both a

catalyst Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

and as part of enzymes. Copper is mainly involved in

redox Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...

reactions throughout the body, but also plays a role in iron transportation in

blood plasma Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intr ...

Production

Copper-64 can be technically reproduced by several different reactions with the most common methods using either a reactor or a

particle accelerator A particle accelerator is a machine that uses electromagnetic fields to propel charged particles to very high speeds and energies, and to contain them in well-defined beams. Large accelerators are used for fundamental research in particle ...

Thermal neutrons The neutron detection temperature, also called the neutron energy, indicates a free neutron's kinetic energy, usually given in electron volts. The term ''temperature'' is used, since hot, thermal and cold neutrons are moderated in a medium with ...

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 The University of Missouri Research Reactor Center (MURR) is home to a tank-type nuclear research reactor that serves the University of Missouri in Columbia, United States. , the MURR is the highest power university research reactor in the U.S. at ...

(MURR) ⁶⁴Cu was produced using high-energy

neutron The neutron is a subatomic particle, symbol or , which has a neutral (not positive or negative) charge, and a mass slightly greater than that of a proton. Protons and neutrons constitute the nuclei of atoms. Since protons and neutrons beh ...

s via the ⁶⁴Zn(n,p)⁶⁴Cu

nuclear reaction In nuclear physics and nuclear chemistry, a nuclear reaction is a process in which two nuclei, or a nucleus and an external subatomic particle, collide to produce one or more new nuclides. Thus, a nuclear reaction must cause a transformatio ...

in high specific activity but low yield. Using a biomedical

cyclotron A cyclotron is a type of particle accelerator invented by Ernest O. Lawrence in 1929–1930 at the University of California, Berkeley, and patented in 1932. Lawrence, Ernest O. ''Method and apparatus for the acceleration of ions'', filed: Jan ...

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

radiopharmaceutical Radiopharmaceuticals, or medicinal radiocompounds, are a group of pharmaceutical drugs containing radioactive isotopes. Radiopharmaceuticals can be used as diagnostic and therapeutic agents. Radiopharmaceuticals emit radiation themselves, which is ...

s for the imaging of a range of conditions. Its beta emissions also raise the possibility of

therapeutic A therapy or medical treatment (often abbreviated tx, Tx, or Tx) is the attempted remediation of a health problem, usually following a medical diagnosis. As a rule, each therapy has indications and contraindications. There are many different ...

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 In drug development, preclinical development, also termed preclinical studies or nonclinical studies, is a stage of research that begins before clinical trials (testing in humans) and during which important feasibility, iterative testing and drug ...

work has shown that ⁶⁴Cu linked to methanephosphonate

functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the rest ...

s has potential as a bone imaging agent.

Neuroendocrine tumors (NETs)

Neuroendocrine tumor Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. They most commonly occur in the intestine, where they are often called carcinoid tumors, but they are also found in the pancreas, lun ...

s (NETs) are localised clinically using a range of

DOTA ''Dota'' is a series of strategy video games by Valve. The series began in 2003 with the release of ''Defense of the Ancients'' (''DotA''), a fan-developed multiplayer online battle arena (MOBA) mod for the video game '' Warcraft III: Reign of ...

based radiopharmaceuticals. For PET imaging these are typically

Gallium-68 Natural gallium (31Ga) consists of a mixture of two stable isotopes: gallium-69 and gallium-71. The most commercially important radioisotopes are gallium-67 and gallium-68. Gallium-67 (half-life 3.3 days) is a gamma-emitting isotope (the gamma r ...

based. A commercial ⁶⁴Cu-

DOTA-TATE DOTA-TATE (DOTATATE, DOTA-octreotate, oxodotreotide, DOTA-(Tyr3)-octreotate, and DOTA-0-Tyr3-Octreotate) is an eight amino acid long peptide, with a covalently bonded DOTA bifunctional chelator. DOTA-TATE can be reacted with the radionuclides ...

product has been

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

approved for localization of

somatostatin receptor Somatostatin receptors are receptors for the ligand somatostatin, a small neuropeptide associated with neural signaling, particularly in the post-synaptic response to NMDA receptor co-stimulation/activation. Somatostatin is encoded by a CRE ...

positive NETs since 2020.

Prostate cancer

The

Bombesin Bombesin is a 14-amino acid peptide originally isolated from the skin of the European fire-bellied toad (''Bombina bombina'') by Vittorio Erspamer ''et al.'' and named after its source. NIHMSID 45053. It has two known homologs in mammals called ...

peptide has been shown to be overexpressed in BB2 receptors in

prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...

. CB-TE2A a stable chelation system for ⁶⁴Cu was incorporated with Bombesin analogs for

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...

and

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

studies of prostate cancer. PET-CT imagining studies showed that it underwent uptake into prostate tumor

xenografts Xenotransplantation (''xenos-'' from the Greek meaning "foreign" or strange), or heterologous transplant, is the transplantation of living cells, tissues or organs from one species to another. Such cells, tissues or organs are called xenograft ...

selectively with decreased uptake into non target tissues. Other preclinical studies have shown that by targeting the

gastrin Gastrin is a peptide hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the pyloric antrum of the stomach, duodenum, and the pancreas. Gastrin ...

-releasing peptide receptor pancreatic and breast cancer can also be detected.

Renal perfusion

Ethylglyoxal bis(

thiosemicarbazone A thiosemicarbazone is an organosulfur compound with the formula H2NC(S)NHN=CR2. Many variations exist, including those where some or all of the N''H'' centers are substituted by organic groups. Thiosemicarbazones are usually produced by condens ...

) (ETS) has potential utility as a PET radiopharmaceutical with the various isotopes of copper. ⁶⁴Cu-ETS has been used for experimental

myocardial, cerebral and tumor

perfusion Perfusion is the passage of fluid through the circulatory system or lymphatic system to an organ or a tissue, usually referring to the delivery of blood to a capillary bed in tissue. Perfusion is measured as the rate at which blood is deliver ...

evaluations, with a linear relationship between the renal uptake and blood flow.

Renal The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

perfusion can also be evaluated with CT or

MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...

instead of PET, but with drawbacks: CT requires administration of potentially

allergenic An allergen is a type of antigen that produces an abnormally vigorous immune response in which the immune system fights off a perceived threat that would otherwise be harmless to the body. Such reactions are called Allergy, allergies. In techni ...

contrast agent A contrast agent (or contrast medium) is a substance used to increase the contrast of structures or fluids within the body in medical imaging. Contrast agents absorb or alter external electromagnetism or ultrasound, which is different from radiop ...

s. MRI avoids use of

ionising radiation Ionizing radiation (or ionising radiation), including nuclear radiation, consists of subatomic particles or electromagnetic waves that have sufficient energy to ionize atoms or molecules by detaching electrons from them. Some particles can travel ...

but is difficult to implement, and often suffers from motion artefacts. PET with ⁶⁴Cu can offer

quantitative Quantitative may refer to: * Quantitative research, scientific investigation of quantitative properties * Quantitative analysis (disambiguation) * Quantitative verse, a metrical system in poetry * Statistics, also known as quantitative analysis ...

measurements of renal perfusion.

Wilson’s disease

Wilson disease Wilson's disease is a genetic disorder in which excess copper builds up in the body. Symptoms are typically related to the brain and liver. Liver-related symptoms include vomiting, weakness, fluid build up in the abdomen, swelling of the legs, ...

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 Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

carriers and

homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

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 External beam radiotherapy (EBRT) is the most common form of radiotherapy (radiation therapy). The patient sits or lies on a couch and an external source of ionizing radiation is pointed at a particular part of the body. In contrast to brachyt ...

because

hypoxia Hypoxia means a lower than normal level of oxygen, and may refer to: Reduced or insufficient oxygen * Hypoxia (environmental), abnormally low oxygen content of the specific environment * Hypoxia (medical), abnormally low level of oxygen in the tis ...

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.

References

{{Reflist Isotopes of copper Positron emitters Radiopharmaceuticals