Simultaneous production of high specific activity 64Cu and 61Co with 11.4 MeV protons on enriched 64Ni nuclei

The ⁶⁴Cu and ⁶¹Co radionuclides were produced simultaneously by irradiation of enriched ⁶⁴Ni on a low energy proton-only cyclotron. Nickel targets were prepared by electrodeposition of enriched ⁶⁴Ni (>95%) on Au backing at thicknesses of 25–225 mg/cm² with efficiencies >99%. Irradiations up to 30 μA for 8 h were performed with 11.4 MeV protons using a water-cooled target mounting. Radiochemical separation of ⁶⁴Cu and ⁶¹Co from ⁶⁴Ni was performed by chromatography of the chlorocomplexes in a single step using an anion exchange resin column with a yield >95%. Using this method, the Ni target material was recovered and re-plated for subsequent production runs with an overall efficiency >96%. The excitation function for the ⁶⁴Ni(p,n)⁶⁴Cu reaction was measured and compared with published values. Experimental thick target saturation yields of 159 mCi/μA for ⁶⁴Cu and 715 μCi/μA for ⁶¹Co were achieved. Typical specific activities of ⁶⁴Cu were found to be 18.8±3.3 Ci/μmol.     

Excitation functions for deuteron induced reactions in natural nickel: Production of no-carrier-added 64Cu from enriched 64Ni targets for positron emission tomography

The excitation functions for the production of ⁶⁴Cu and other radionuclides by the deuteron irradiation of natural Ni targets have been measured up to 19 MeV incident energy. The excitation function for the ⁶⁴Ni(d, 2n)⁶⁴Cu reaction shows a maximum effective cross section of 7.2±0.9 mbarn at 16.2 MeV for the natural Ni target. Data have been used for the production of large quantities of ⁶⁴Cu by the deuteron irradiation of enriched (96.4%) ⁶⁴Ni targets. The radiochemical extraction procedures developed can produce either carrier-free ⁶⁴Cu or utilize a small amount (50 μg) of carrier. The thick target yield of ⁶⁴Cu is 107 ± 16 GBq/C (10.5 ± 1.6 mCi/μ Ah) and the contamination with ⁶¹Cu is only 0.29% at EOB. Data on the production yields of ⁶¹Cu, ⁶⁴Cu, ⁵⁷Ni, ⁵⁵Co, ⁵⁶Co ⁵⁷Co and ⁵⁸Co during the deuteron irradiation of natural Ni and enriched ⁶⁴Ni targets are presented.     

Activation cross-sections of proton induced reactions on natural Ni up to 65 MeV

Production cross-sections of the ^natNi(p,x)^60,61Cu, ^56,57Ni, ^55,56,57,58Co nuclear reactions were measured in five experiments up to 65 MeV by using a stacked foil activation technique. The results were compared with the available literature values, predictions of the nuclear reaction model codes ALICE-IPPE, TALYS-1.4, and extracted data from the TENDL-2012 library. Spline fits were made on the basis of selected data, from which physical yields were calculated and compared with the literature values. The applicability of the ^natNi(p,x)⁵⁷Ni, ⁵⁷Co reactions for thin layer activation (TLA) was investigated. The production rate for ⁵⁵Co was compared for proton and deuteron induced reactions on Ni.     

Excitation functions of proton-induced reactions on natFe and enriched 57Fe with particular reference to the production of 57Co

Excitation functions of the reactions ^natFe(p,xn)^55,56,57,58Co, ^natFe(p,x)⁵¹Cr, ^natFe(p,x)⁵⁴Mn, ⁵⁷Fe(p,n)⁵⁷Co and ⁵⁷Fe(p,α)⁵⁴Mn were measured from their respective thresholds up to 18.5 MeV, with particular emphasis on data for the production of the radionuclide ⁵⁷Co (T_1/2=271.8 d). The conventional stacked-foil technique was used, and the samples for irradiation were prepared by an electroplating or sedimentation process. The measured excitation curves were compared with the data available in the literature as well as with results of nuclear model calculations. From the experimental data, the theoretical yields of the investigated radionuclides were calculated as a function of the proton energy. Over the energy range E_p=15→5 MeV the calculated yield of ⁵⁷Co from the ⁵⁷Fe(p,n)⁵⁷Co process amounts to 1.2 MBq/μA h and from the ^natFe(p,xn)⁵⁷Co reaction to 0.025 MBq/μA h. The radionuclidic impurity levels are discussed. Use of highly enriched ⁵⁷Fe as target material would lead to formation of high-purity ⁵⁷Co.     

An Am/Be neutron source and its use in integral tests of differential neutron reaction cross-section data

An Am/Be neutron source, installed recently at the Rajshahi University, is described. Neutron flux mapping was done using the nuclear reactions ¹⁹⁷Au(n,γ)¹⁹⁸Au, ¹¹³In(n,γ)^114mIn, ¹¹⁵In(n,n′γ)^115mIn and ⁵⁸Ni(n,p)⁵⁸Co. An approximate validation of the neutron spectral shape was done using five neutron threshold detectors and the iterative unfolding code SULSA. Integral cross sections of the reactions ⁵⁴Fe(n,p)⁵⁴Mn, ⁵⁹Co(n,p)⁵⁹Fe and ⁹²Mo(n,p)^92mNb were measured with fast neutrons (E_n>1.5 MeV) and compared with data calculated using the neutron spectral distribution and the excitation function of each reaction given in data libraries: an agreement within±6% was found.     

Nuclear model analysis of excitation functions of proton,deuteron and α-particle induced reactions on nickel isotopes for production of the medically interesting copper-61

Excitation functions of the ⁶¹Ni(p,n)⁶¹Cu, ⁶²Ni(p,2n)⁶¹Cu, ⁶⁰Ni(d,n)⁶¹Cu and ⁵⁸Ni(α,p)⁶¹Cu reactions were analyzed with respect to the production of ⁶¹Cu (T_½=3.33 h), a promising radionuclide for PET imaging. The nuclear model codes EMPIRE and TALYS reproduced the experimental data of all reactions well, except those for the (d,n) process. The fitted excitation functions were employed to calculate the integral yield of ⁶¹Cu in all reactions. The amounts of the possible impurities ⁶²Cu and ⁶⁰Cu were assessed. A validation of the evaluated (p,xn) data was attempted.     

Measurement of the fission neutron spectrum averaged cross sections for the 95Mo(n,p)95Nb, 92Mo(n, α)89Zr, 90Zr(n, 2n)89Zr and 60Ni(n,p)60Co reactions

The average cross-sections in a fission-type reactor neutron spectrum are determined experimentally for the reactions: ⁹²Mo (n, a) ⁸⁹Zr, ⁹⁰Zr (n, 2n) ⁸⁹Zr and ⁶⁰Ni (n, p) ⁶⁰Co. The determined cross sections are in the ranges of the reported values in literature. A method for determining the cross sections in relative way is introduced. It replaces the cross sections and the nuclear data by a composite nuclear data constant which can be calculated and determined experimentally. It is shown that the uncertainties of determining these constants experimentally are mainly lower than the calculated ones. The consequences of using this constant in neutron activation analysis are briefly discussed.     

Modern dosimetric tools for 60Co irradiation at high containment laboratories

Abstract

Purpose: To evaluate an innovative photo-fluorescent film as a routine dosimetric tool during ⁶⁰Co irradiations at a high containment biological research laboratory, and to investigate whether manufacturer-provided chamber exposure rates can be used to accurately administer a prescribed dose to biological specimens.

Materials and methods: Photo-fluorescent, lithium fluoride film dosimeters and National Institutes of Standards and Technology (NIST) transfer dosimeters were co-located in a self-shielded ⁶⁰Co irradiator and exposed to γ-radiation with doses ranging from 5–85 kGy. Film dose-response relationships were developed for varying temperatures simulating conditions present when irradiating infectious biological specimens. Dose measurement results from NIST transfer dosimeters were compared to doses predicted using manufacturer-provided irradiator chamber exposure rates.

Results: The film dosimeter exhibited a photo-fluorescent response signal that was consistent and nearly linear in relationship to γ-radiation exposure over a wide dose range. The dosimeter response also showed negligible effects from dose fractionization and humidity. Significant disparities existed between manufacturer-provided chamber exposure rates and actual doses administered.

Conclusion: This study demonstrates the merit of utilizing dosimetric tools to validate the process of exposing dangerous and exotic biological agents to γ-radiation at high containment laboratories. The film dosimeter used in this study can be utilized to eliminate potential for improperly administering γ-radiation doses.     

Study of the excitation function for the deuteron induced reaction on 64Ni(d,2n) for the production of the medical radioisotope 64Cu

The production of ⁶⁴Cu, a radioisotope of considerable interest for the application in nuclear medicine for PET imaging and radioimmunotherapy, was investigated by deuteron bombardment of enriched ⁶⁴Ni target up to E_d=20.5 MeV. The experimental excitation function for the reaction ⁶⁴Ni(d,2n)⁶⁴Cu was measured using the stacked foil irradiation technique followed by HPGe γ-ray analysis at 1346 keV and is compared with earlier literature values. Cross-section data for the ⁶⁴Ni(d,p)⁶⁵Ni reaction are determined for the first time. Thick target yields are derived and compared with results of other production routes.     

Radiosensitivity of C. Parvum-stimulated Spleen to Acute 60Co and Low Dose Rate 137Cs and 252Cf Irradiation

Summary

Stimulation of spleen growth by injection of C. parvum led to rapid organ enlargement, and acute ⁶⁰Co or low dose rate (LDR) ¹³⁷Cs or ²⁵²Cf irradiation reduced the maximum enlargement achieved. Irradiations were carried out 3 days after CP injection. Sigmoid dose–response curves were observed for the fraction of maximum enlargement achieved after acute ⁶⁰Co. After low dose rate ¹³⁷Cs or ²⁵²Cf irradiation, exponential dose-response curves of very different slope were observed. Acute and LDR γ-radiation produced reduced effects in the stimulated and proliferating spleen compared to LDR ²⁵²Cf neutron/γ-irradiation which had relative biological effectiveness = 4·0 versus low dose rate ¹³⁷Cs.     

Energy measurement of D-T neutrons near the target using the ratio of the (n, 2n) and (n,p) reaction of nickel

For the first time, a sensitive method based on the cross-section ratio of ^58g+mCo/⁵⁷Ni for the determination of axial and angular variation of energy of D-T neutrons near the tritium target has been presented. The results are compared with the “Zr/Nb” ratio method and with theoretically calculated values. The effect of scattered neutrons from the target backing and the surrounding material has also been investigated. The impact of the energy variation on the activation analysis or the cross-section measurement is discussed.     

Study of the Ni(p,x)Ni process up to 44 MeV for monitor Purposes

Cross sections have been measured from 14 up to 44 MeV for proton induced nuclear processes on natural nickel leading to the production of ⁵⁷Ni (T_1/2=36.1 h) using the stacked foil method. We have also investigated the contribution of background neutron induced reactions to the production of ⁵⁷Ni. On the basis of the presented experimental work and the available literature results it can be concluded that the ^natNi(p, x)⁵⁷Ni process can be used very effectively for monitoring proton beams in the investigated energy range.     

Evaluation of excitation functions of proton and deuteron induced reactions on enriched tellurium isotopes with special relevance to the production of iodine-124

Cross-section data for the production of medically important radionuclide ¹²⁴I via five proton and deuteron induced reactions on enriched tellurium isotopes were evaluated. The nuclear model codes, STAPRE, EMPIRE and TALYS, were used for consistency checks of the experimental data. Recommended excitation functions were derived using a well-defined statistical procedure. Therefrom integral yields were calculated. The various production routes of ¹²⁴I were compared. Presently the ¹²⁴Te(p,n)¹²⁴I reaction is the method of choice; however, the ¹²⁵Te(p,2n)¹²⁴I reaction also appears to have great potential.     

Development and validation of the 57Co assay for determining the ligand to antibody ratio in bifunctional chelate/antibody conjugates for use in radioimmunotherapy

Introduction

The ligand to antibody ratio is an important characteristic of a chelate/antibody conjugate. It has been widely reported that if the ratio is too high, there will be detrimental effects on immunoreactivity and biodistribution; conversely, if the ratio is too low, the radionuclide may not bind efficiently, and the stability and the specific activity will be reduced. There are little published data on the accuracy or precision of the ⁵⁷Co assay. The UK Clinical Trials Regulations state that “systems with procedures that assure the quality of every aspect of the trial should be implemented”. The aims of this study were to assess the reliability and accuracy of the ⁵⁷Co binding assay and validate it against defined criteria.

Method

Thirty-two serial assays were assessed for reliability. Two batches of conjugated antibody were also analysed by matrix-assisted laser desorption/ionisation time of flight (MALDI-TOF) mass spectrometry (MS) to allow the comparison of the functional test with a physical method.

Results

Reliability: The coefficient of variation was 0.13. Accuracy: There was 9% variation between the ⁵⁷Co binding assay and MALDI-TOF MS results.

Conclusion

A detailed method for the ⁵⁷Co ligand to antibody test is described that allows a discrete value to be obtained. The assay was validated as fit for purpose against target values of coefficient of variation <0.20, accuracy±10%, over a permissive range of 0.5–3.0 ligand to antibody ratio.     

Nuclear model analysis of excitation functions of proton and deuteron induced reactions on 64Zn and 3He- and α-particle induced reactions on 59Co leading to the formation of copper-61: Comparison of major production routes

Cross section data for formation of the medically important radionuclide ⁶¹Cu (T_½=3.33 h) in proton and deuteron induced reactions on enriched ⁶⁴Zn and in ³He- and α-particle induced reactions on ⁵⁹Co were analyzed by using the nuclear model calculational codes, EMPIRE and TALYS. A well-defined statistical procedure was then employed to derive the recommended excitation functions, and therefrom to obtain integral yields. A comparison of major production routes of ⁶¹Cu was done.     

Production of carrier free 109Cd, 57Co and 54Mn from a composite cyclotron target of enriched silver-109 and iron-56

A method is presented for the production and separation of carrier free ¹⁰⁹Cd, ⁵⁷Co and ⁵⁴Mn from a deuteron bombarded composite enriched silver-109 and iron-56 cyclotron target. Silver is removed from the matrix by reduction with hydrazine and the following ion exchange separation employs cation and anion exchange columns in tandem using hydrochloric acid/acetone and hydrobromic/nitric acid as the main eluting agents for the two respective columns. Overall efficiency rates for the three product radionuclides are in excess of 99%.     

Excitation functions of proton induced nuclear reactions on natural nickel for monitoring beam energy and intensity

Cross sections have been measured up to 30 MeV for proton induced nuclear reactions on natural nickel targets leading to the production of ⁵⁷Ni, ⁵⁷Co, ⁵⁶Co and ⁵⁵Co. The measured excitation functions are compared with the published data from the point of view of their potential use as monitor reactions for beam performance.     

Post-irradiation viability and cytotoxicity of natural killer cells isolated from human peripheral blood using different methods

Purpose We compared the pre- and post-irradiation viability and cytotoxicity of human peripheral natural killer cell (NK) populations obtained using different isolation methods.

Material and methods Three methods were used to enrich total NK cells from buffy coats: (I) a Ficoll-Paque gradient, plastic adherence and a nylon wool column; (II) a discontinuous Percoll gradient; or (III) the Dynal NK cell isolation kit. Subsequently, CD16⁺ and CD56⁺ NK cell subsets were collected using (IV) flow cytometry or (V) magnetic-activated cell sorting (MACS) NK cell isolation kits. The yield, viability, purity and cytotoxicity of the NK cell populations were measured using trypan blue exclusion, flow cytometry using propidium iodide and ⁵¹Cr release assays after enrichments as well as viability and cytotoxicity after a single radiation dose.

Results The purity of the preparations, as measured by the CD16⁺ and CD56⁺ cell content, was equally good between methods I–III (p?=?0.323), but the content of CD16⁺ and CD56⁺ cells using these methods was significantly lower than that using methods IV and V (p?=?0.005). The viability of the cell population enriched via flow cytometry (85.5%) was significantly lower than that enriched via other methods (99.4–98.0%, p?=?0.003). The cytotoxicity of NK cells enriched using methods I–III was significantly higher than that of NK cells enriched using methods IV and V (p?=?0.000). In vitro the NK cells did not recover cytotoxic activity following irradiation. In addition, we detected considerable inter-individual variation in yield, cytotoxicity and radiation sensitivity between the NK cells collected from different human donors.

Conclusions The selection of the appropriate NK cell enrichment method is very important for NK cell irradiation studies. According to our results, the Dynal and MACS NK isolation kits best retained the killing capacity and the viability of irradiated NK cells.     

Production of cobalt-55, a short-lived,positron emitting radiolabel for bleomycin

The production and radiochemical separation of ⁵⁵Co from deuteron irradiation of enriched ⁵⁴Fe target is described. Methods used for the recovery and reuse of the target material (⁵⁴Fe) are also described. The yield of ⁵⁵Co at 12 MeV incident deuteron energy is 1.7 mCi per μAh at end of bombardment and the contamination with ⁵⁷Co is 0.016%. The ⁵⁵Co produced is chelated to bleomycin and used for tumour imaging with a positron emission tomographic camera based on multi-wire proportional chamber detectors.