Production Of 64Cu Research Articles

Theoretical estimation of 64Cu production with neutrons emitted during 18F production with a 30 MeV medical cyclotron

PurposeThis work presents the theoretical estimation of a combined production of 18F and 64Cu isotopes for PET applications. 64Cu production is induced in a secondary target by neutrons emitted during a routine 18F production with a 30MeV cyclotron: protons are used to produce 18F by means of the 18O(p,n)18F reaction on a [18O]-H2O target (primary target) and the emitted neutrons are used to produce 64Cu by means of the 64Zn(n,p)64Cu reaction on enriched zinc target (secondary target). MethodsMonte Carlo simulations were carried out using Monte Carlo N Particle eXtended (MCNPX) code to evaluate flux and energy spectra of neutrons produced in the primary (Be+[18O]-H2O) target by protons and the attenuation of neutron flux in the secondary target. 64Cu yield was estimated using an analytical approach based on both TENDL-2015 data library and experimental data selected from EXFOR database. ResultsTheoretical evaluations indicate that about 3.8 MBq/μA of 64Cu can be obtained as a secondary, ‘side’ production with a 30MeV cyclotron, for 2h of irradiation of a proper designed zinc target. Irradiating for 2h with a proton current of 120 μA, a yield of about 457 MBq is expected. Moreover, the most relevant contaminants result to be 63,65Zn, which can be chemically separated from 64Cu contrarily to what happens with proton irradiation of an enriched 64Ni target, which provides 64Cu mixed to other copper isotopes as contaminants. ConclusionsThe theoretical study discussed in this paper evaluates the potential of the combined production of 18F and 64Cu for medical purposes, irradiating a properly designed target with 30MeV protons. Interesting yields of 64Cu are obtainable and the estimation of contaminants in the irradiated zinc target is discussed.

Industrial-Scale Synthesis of Intrinsically Radiolabeled 64CuS Nanoparticles for Use in Positron Emission Tomography (PET) Imaging of Cancer

Synthesis of intrinsically radiolabeled nanoparticles is an emerging concept in cancer theranostics and is expected to play an imperative role in translating nanotechnology research into the nuclear medicine industry. In order to reduce reliance on cyclotron produced 64Cu (t1/2 = 12.7 h, EC 45%, β+ 17.9%, β– 37.1%) and increase global accessibility of this radioisotope for preclinical and clinical investigations, we have explored the feasibility of using neutron-activated 64Cu produced in research reactors for potential use in cancer theranostics. A viable strategy has been developed for production of 64Cu in medium-flux research reactors and its utilization toward industrial-scale (GBq level) synthesis of intrinsically radiolabeled 64CuS nanoparticles (∼30 nm particle size). The synthesis procedure was easily executable in a hot cell equipped with remotely operable gadgets and 64CuS nanoparticles could be synthesized in a form suitable for clinical administration. The stability of the nanoparticles under...

A novel method for determination of copper in zinc destined to 64Cu production in a nuclear reactor

The assay of copper in zinc matrixes by reactor activation analysis presents significant difficulties, since the practicable capture reactions, 63Cu(n,γ)64Cu and 65Cu(n,γ)66Cu, are interfered by 64Zn(n,p)64Cu and 66Zn(n,p)66Cu reactions, as dominant activities. Taking into account this fact, the possibility of developing a method for copper determination in zinc compounds based on the measurement of 66Cu/64Cu activity ratios is discussed. The theoretical fundamentals are formulated; the experimental application for the application to the control of zinc compounds destined to the production of 64Cu is described.

On the formation of non-radioactive copper during the production of 64Cu via proton and deuteron-induced nuclear reactions on enriched 64Ni targets

Routine production of 64Cu commonly exploits the 64Ni(p,n) or 64Ni(d,2n) reactions. Above specific threshold energies, however, non-radioactive 63Cu and/or 65Cu are also co-produced. The non-radioactive (cold) Cu can significantly decrease the specific activity (SA) of 64Cu-labelled radiopharmaceuticals. Based on nuclear model calculations for the formation of non-radioactive Cu isotopes, theoretical specific activities (TSA) for 64Cu were estimated. Reported current production methods, however, often yield SA values that are lower than the corresponding TSA predictions by more than an order of magnitude. Most of the non-radioactive Cu causing this has been found to originate from sources other than co-production, indicating that there is still significant potential for method improvement.

Production of 61Cu by the natZn(p,α) reaction: improved separation and specific activity determination by titration with three chelators

The cyclotron-based production of positron-emitting 61Cu using the (p,α) reaction at 11.7 MeV was investigated starting from natural-zinc (natZn) and enriched 64Zn-foil targets, as well as its subsequent purification. For natZn, a combination of three resins were assessed to separate 61Cu from contaminating 66,67,68Ga and natZn. The specific activity of the purified 61Cu determined using ICP-MS analysis ranged from 143.3 ± 14.3(SD) to 506.2 ± 50.6 MBq/µg while the titration method using p-SCN-Bn-DOTA, p-SCN-Bn-NOTA and diamsar gave variable results (4.7 ± 0.2–412.5 ± 15.3 MBq/µg), with diamsar lying closest to the ICP-MS values. Results suggest that the p-SCN-Bn-DOTA and p-SCN-Bn-NOTA titration methods are significantly affected by the presence of trace-metal contaminants.

Evaluated activation cross-sections and intercomparison of the production parameters for the medically relevant radioisotopes 64Cu and 86Y

A theoretical study of the nuclear reaction cross-section for the production of 64Cu and 86Y was performed from the nuclear reactions 64Ni(p, n) 64Cu, 64Ni(d, 2n) 64Cu, 66Zn(d, α)64Cu, 68Zn(p, n α)64Cu, 86Sr(p, n) 86gY, 87Sr(p, 2n) 86gY and 88Sr(p, 3n) 86gY. The calculations were performed using three codes EMPIRE, TALYS and ALICE-IPPE. The excitation function curves for the investigated reactions have been constructed from the enriched targets using 64Ni, 66Zn, 68Zn, 86Sr, 87Sr and 88Sr. The calculated excitation functions and the experimental data were compared. Mean standardized deviation, mean relative deviation and mean ratio statistical parameters were introduced to control the quality of the fitting between both the experimentally and the theoretically calculated cross-sections.

Development of cost effective method for production of 64Cu from natNi

A natNi foil was used for the production of 64Cu via 64Ni(p,n)64Cu nuclear reaction when the necessary investment for target material (350 mg) is 50 times less using the natNi instead of 64Ni. The produced 32.2 ± 1.8 MBq of “no carrier added” 64Cu is sufficient for 10 mice trials on small animal PET. The radionuclide contamination was <13 ± 12 kBq for 55Co and 4 ± 2 kBq for 57Ni comparing to minimum detectable activity and only 52 ± 2 kBq of 61Cu was in 64Cu due to the modified ion exchange separation. The concentration of Fe(III) was maintained under 1.7 ppm by precipitation and filtering of Fe(OH)3 due to the chemical purity was required.

Radiochemical measurement of neutron-spectrum averaged cross sections for the formation of 64Cu and 67Cu via the (n,p) reaction at a TRIGA Mark-II reactor: Feasibility of simultaneous production of the theragnostic pair 64Cu/67Cu

Abstract Integral cross sections of the 64Zn(n, p)64Cu and 67Zn(n, p)67Cu reactions were measured for the fast neutron spectrum of TRIGA Mark-II reactor at Savar, Dhaka, Bangladesh. A clean radiochemical separation was performed to isolate the copper radionuclides from the target element zinc. The radioactivities produced in the irradiation were measured by HPGe γ-ray spectroscopy. The neutron flux over the energy range 0.5–20 MeV was determined using the 58Ni(n, p)58Co monitor reaction. The measured results amount to 28.9 ± 2.0 mb and 0.84 ± 0.07 mb for the formation of 64Cu and 67Cu, respectively. These values are slightly lower than the respective values for a pure fission spectrum. The present results were compared with data calculated using the neutron spectral distribution and the recently critically analysed excitation function of each reaction given in the literature. The good agreement validates the reliability of those excitation functions. The feasibility of simultaneous production of 64Cu and 67Cu with fast neutrons is discussed.

Specific activity measurement of 64Cu: A comparison of methods

Effective specific activity of 64Cu (amount of radioactivity per µmol metal) is important in order to determine purity of a particular 64Cu lot and to assist in optimization of the purification process. Metal impurities can affect effective specific activity and therefore it is important to have a simple method that can measure trace amounts of metals. This work shows that ion chromatography (IC) yields similar results to ICP mass spectrometry for copper, nickel and iron contaminants in 64Cu production solutions.

Automation of 64Cu production at Turku PET Centre

At Turku PET Centre automation for handling solid targets for the production of 64Cu has been built. The system consists of a module for moving the target from the irradiation position into a lead transport shield and a robotic-arm assisted setup for moving the target within radiochemistry laboratory. The main motivation for designing automation arises from radiation hygiene.

A simple and efficient method of nickel electrodeposition for the cyclotron production of 64Cu

Nickel targets for the cyclotron production of 64Cu were prepared by electrodeposition on a gold backing from nickel chloride solutions using boric acid as buffer. Parameters studied were nickel chloride and boric acid concentration, temperature and current density. All plating conditions studied were successful obtaining efficiencies of approximately 90% in 2–3h, reaching almost quantitative plating (>97%) in 10–20h depending on the current density. All plated targets withstood proton irradiations up to 40µA for 2h. Recovered nickel was successfully recycled and reused with an overall efficiency >95%.

Production and Quality Control of &amp;lt;sup&amp;gt;64&amp;lt;/sup&amp;gt;Cu from High Current Ni Target

A new production method of no-carrier-added 64Cu was tested using a new target prepared by electroplating of Ni on a silver layer (thickness 35 μm) previously electroplated on a pure copper target support. This method meets cost effective production and quality of the produced 64Cu criteria. The quality of the electroplated layers has been tested under the bombardment by more than 200 μA of proton beam using water cooled target system. A separation and purification setup was elaborated to produce high quantity and high specific activity of 64CuCl2 suitable for labeling different ligands in order to be used in therapy and diagnosis. A semi-automated target dissolution and separation system has been developed and achieved for 64Cu production. The separation chemistry is based on a chromatographic column system.

Automated production of 64Cu prepared by 18 MeV cyclotron

64Cu (T1/2 = 12,7 h, β− 37,1 %, β+ 17,9 %, EC 41 %) is a useful radioisotopes for positron emission tomography radiopharmaceutical. We used the reaction route 64Ni(p,n)64Cu for the 64Cu preparation. A basic disadvantage of this route, a high price of the enriched target material, was eliminated by using very simple recycling procedure. Compact solid target irradiation system was installed at the end of the external beam line of the IBA Cyclone 18/9 cyclotron. In this paper, the irradiation of 64Ni target and separation of 64Cu from a target material is described. The separation was achieved by anion exchange chromatography with HCl as a elution solution. The distribution ratio for different HCl concentrations on Bio-Rad AG1-X8 and elution profile of 64Cu were investigated. 64Cu production rate for 100 mg 64Ni of 99.09 % purity (ISOFLEX) on gold target was 104 MBq/μAh. The activity of the product was checked by ionisation chamber (Curiementor), gamma spectrometry using a HPGe detector and liquid scintillation counting using the triple-to-double coincidence ratio method. The separation process of 64Cu was made in a home-made separation module.

Module-assisted preparation of 64Cu with high specific activity

In this work the production of 64Cu via the 64Ni(p,n)64Cu reaction with optimized conditions for low current irradiation is presented. Different target setups and cleaning steps for lowering metal contaminations in the product were applied. 64Cu with high specific activities up to 1685GBq/μmol was produced despite low overall activity (∼4.2GBq per run). The module processing leads to a highly reproducible, reliable product quality (<1μg Cu and <7μg Ni). Besides its diagnostic value 64Cu may be of interest even for therapeutic purposes due to its decay characteristics.

Production of 61Cu using natural cobalt target and its separation using ascorbic acid and common anion exchange resin

(61)Cu was produced by (nat)Co(α, xn)(61)Cu reaction. (61)Cu production yield was 89.5 MBq/μAh (2.42 mCi/μAh) at the end of irradiation (EOI). A simple radiochemical separation method using anion exchange resin and ascorbic acid has been employed to separate the product radionuclide from inactive target material and co-produced non-isotopic impurities. The radiochemical separation yield was about 90%. Radiochemical purity of (61)Cu was >99% 1 h after EOI. Final product was suitable for making complex with N(2)S(2) type of ligands.

Preparation and characterization of nickel targets for cyclotron production of 64Cu

The reaction route 64Ni(p,n)64Cu is very popular for the preparation of 64Cu because its entrance channel is accessible at low energies and yield of reaction is quite high. However, a high price of the enriched 64Ni is a disadvantage of this reaction path; hence, preparation of a chemically pure nickel targets for the production of 64Cu using COSTIS (Compact Solid Target Irradiation System) is of a great research interest. In this paper, effects of boric acid, composition of electrolytic bath and electrochemical process conditions on the quality of nickel films deposited on 2 mm thick gold or platinum disc targets were investigated. Chemical purity of the electrodeposited nickel was measured by the Auger electron spectroscopy and the surface quality of targets was studied microscopically (SEM). A SRIM program was used for a thickness target calculation. COSTIS target station was installed at the end of the external beam line of the IBA Cyclone 18/9 cyclotron, and the irradiation surface of target was optimized. The target station has been equipped with Al or Nb window foil in the front of the target to degrade the beam energy to an optimal value.

Characterisation of a Cu selective resin and its application to the production of 64Cu

Cu isotopes (e.g. 64Cu) increasingly find use in radiopharmaceutical applications, accordingly fast and reliable methods for the production of these isotopes are needed. The aim of the presented project is the characterization of a Cu selective extraction chromatographic resin for the fast and selective separation of Cu radionuclides, e.g. from irradiated targets. The characterisation of the resin includes the determination of weight distribution factors Dw of Cu, Ni, Zn and other potentially interfering elements and impurities for varying acids and pH values, the influence of macro amounts of Ni and Zn on the extraction of Cu as well as the influence of other potential interferents. Based on the obtained results, a method for the separation of Cu and its purification from irradiated Ni or Zn targets was developed and tested on simulated Ni and Zn targets.

Comparison of nuclear data of 64Cu production using an accelerator by TALYS 1.0 code

The extensive use of 64Cu (T1/2 = 12.7 h) as a positron and electron emitter radioisotope in recent years has ensured its potential to serve a dual role in the development of molecular agents in PET and radioimmunotheraphy drugs in oncology. The TALYS 1.0 code was used to calculate excitation functions for induced proton, deuteron and alfa-particles on 64Zn, 66Zn, 67Zn, 68Zn, 70Zn, 62Ni, and 64Ni up to 50 MeV. According to the data acquired by the TALYS 1.0 code, thick-target integral yield of the induced charged particles on the enriched targets was achieved.

Alternative method for 64Cu radioisotope production

The method for 64Cu production based on a 64Ni target using an 18 MeV proton energy beam was developed. The studies on the optimisation of targetry for the 18 MeV proton bombardments were performed in terms of the cost-effective target utilisation and purity of the 64Cu product. The thickness-specific 64Cu yield (μCi/(μA×μm)) was introduced into the optimisation calculation with respect to cost-effective target utilisation. A maximum target utilisation efficacy factor (TUE) was found for the proton energy range of 2.5–13 MeV with corresponding target thickness of 36.2 μm. With the optimised target thickness and proton energy range, the 64Ni target thickness saving of 45.6% was achieved, while the overall 64Cu yield loss is only 23.9%, compared to the use of the whole effective proton energy range of 0–18 MeV with target thickness of 66.6 μm. This optimisation has the advantage of reducing the target amount to a reasonable level, and therefore the cost of the expensive 64Ni target material. The 64Ni target electroplated on the Au–Tl multi layer coated Cu-substrate was a new and competent design for an economic production of high quality 64Cu radioisotope using an 18 MeV proton energy cyclotron or a 30 MeV cyclotron with proton beam adjustable to 18 MeV. In this design, the Au coating layer plays a role of protection of “cold” Cu leakage from the Cu substrate and Tl serves to depress the proton beam energy (from 18 MeV to the energy optimised value 13 MeV). The ion exchange chromatographic technique with a gradient elution was applied to improve the 64Cu separation with respect to reducing the processing time and control of 64Cu product quality.

A simple Cu-64 production and its application of Cu-64 ATSM

One of the positron emission radionuclides, 64Cu, has been reported to be a particularly effective radioisotope in PET imaging study. This utility of 64Cu depends on the chemical stability in water with proper energy and half-life as γ-emitters. Hence, we tried to develop a simple method for producing this isotope using an old cyclotron model in our site (50 MeV, Scantronics co.). In particular, we designed the equipments of enrich 64Ni plating system and radioactive 64Cu separation using plastic cartridge column; 64Ni plating system on gold foil which located in the 13° angle target toward beam irradiation. For the nuclear reaction of 64Cu, it was applied to 64Ni(p, n) 64Cu at low energy under the degrader composed of Al and Ta foils. After beam irradiation, 64Cu was identified by multichannel analyzer installed for a HPGe detector and its utility was certified by the microPET images of 64Cu-ATSM (CT-26 tumor bearing mouse as reported previously). The image quality of 64Cu was also very similar to that of 18F radioisotope in microPET scanner. In conclusion, a method of 64Cu production and its application was successfully established in old cyclotron having high energy.