18F Production Research Articles

Neutron spectrum measurements inside a self-shielded cyclotron during 18F production using a single-cylindrical neutron spectrometer with gold and indium activation foils

The Single-Cylindrical Neutron Spectrometer (SCNS) is a single moderated spectrometer in the form of a cylinder with a diameter of 8 cm and a length of 16 cm. Seven Au activation foil type neutron detectors are installed on the moderator axis with varying distances. This spectrometer is used to measure the neutron spectrum in self-shielded cyclotron during 18F production using a proton of 11 MeV and a beam current of 25 µA for 70 min. The detector response was calculated using MCNPX 2.7. The measurement results obtained activity of 198Au and 116mIn and were validated with simulation using MCNPX. With the detector response values and detector activity from the measurements, a neutron spectrum was obtained using the unfolding technique using the UMG program. The neutron spectrum from measurements using SCNS with Au and In activation foil detectors has a difference of 8 %. Meanwhile, with the MCNPX calculation results, the measurement results using the Au foil are 1 % while with the In foil it is 10 %.

Optimised production of technetium-94m for PET imaging by proton-irradiation of phosphomolybdic acid in cyclotron liquid target

Natural-abundance phosphomolybdic acid (H3(Mo12PO40) ‧12H2O, 0.181–0.552 g Mo/mL) solutions were irradiated with 12.9 MeV protons on a GE PETtrace cyclotron using an adapted standard liquid target. Technetium-94m (94mTc) was produced through the 94Mo(p,n)94mTc nuclear reaction with saturation yields of up to 53 ± 6 MBq/μA. End of bombardment activities of 161 ± 17 MBq and 157 ± 7 MBq were achieved for the 0.552 g Mo/mL solution (10 μA for 30 min) and 0.181 g Mo/mL solution (15 μA for 60 min), respectively. No visible degradation of the niobium target body and foil were seen during the irradiations of up to 15 μA for 60 min. The produced 94mTc was separated from the target phosphomolybdic acid solution with >98% recovery using an aqueous biphasic extraction resin. Compared to previous reported liquid target methods for 94mTc production, the better production yield, in-target solution stability during irradiation and 94mTc separation recovery of phosphomolybdic acid makes it a very promising target material for routine clinical 94mTc production at medical facilities with liquid targets already installed for 18F production.

Application of reactor dosimetry techniques for source term validation in F-18 production with a medical cyclotron

Imaging techniques such as positron emission tomography need radionuclides that can be produced with cyclotrons. The involved nuclear reactions mostly produce neutron and gamma radiation, which must be shielded. In order to be able to determine the required thickness of the shielding for a newly bought medical cyclotron, corresponding radiation protection calculations were carried out. The necessary neutron source term was supplied by the manufacturer. To verify this source term, additional source terms were calculated with the MCNP6 and the FLUKA code packages. The results with the source, on base of code internal nuclear models, produced comparable results, but the neutron yield with the source supplied by the manufacturer turned out to be lower by a factor of about 5. To validate the results, experiments were carried out on an already existing cyclotron. Neutron fluence was measured with standard monitors which are used in reactor dosimetry. The experiments were performed during regular 18F production. Activities of the nuclides were measured by gamma spectroscopy and compared with the calculated activities.

Characterization of the neutron flux on the surface of a liquid water target intended for 18F production

18F is an important radioisotope used in nuclear medicine for diagnostic purposes. It is produced most often via 18O (p,n)18F reaction. During its production, the oxygen contained in the H218O molecules placed in the cooled target is irradiated by accelerated protons. The production of each 18F atom is accompanied by anisotropic high-energy neutron emission, which is a problem for ensuring radiation safety. These neutrons are responsible for the high radiation dose in a cyclotron pit during 18F production as well as for activation of cyclotron components or might be responsible even for target material changes due to their high penetration properties. A precise characterization of a neutron field on the surface of the liquid water target, used for 18F production, is presented. The neutron flux characterization is performed both by using large-area activation detectors and stilbene detectors at 1 m from the target in a forward direction. The experiments show significant discrepancies between calculated and measured reaction rates in higher threshold reactions 58Ni(n,x)57Co and 51V (n,α)48Sc, confirming that the current neutron production reaction models are not suitable for the characterization of the secondary neutrons leaking from the target.

Assessment of radionuclide impurities in [18F]fluoromethylcholine ([18F]FMCH).

[18F]Fluoromethylcholine ([18F]FMCH) is a radiopharmaceutical used in positron emission tomography (PET) imaging for the study of prostate, breast, and brain tumors. It is usually synthesized in cyclotron facilities where 18F is produced by proton irradiation of [18O]H2O through 18O(p,n)18F reaction. Due to the activation of target materials, the bombardment causes unwanted radionuclidic impurities in [18O]H2O, that need to be removed during the radiopharmaceutical synthesis. Thus, the aim of this study is to quantify the radionuclide impurities in the 18F production process and in the synthesized [18F]FMCH, demonstrating the radionuclidic purity of this radiopharmaceutical. Long-lived radionuclide impurities were experimentally assessed using high-resolution gamma and liquid scintillation spectrometries, while short-lived impurities were monitored analyzing the decay curve of the irradiated [18O]H2O with an activity calibrator. As spectrometric radionuclide library, a Geant4 Monte Carlo simulation of the 18F-target assembly was previously performed. 3H, 52,54Mn, 56,57,58Co, 95m,96Tc, 109Cd, and 184Re were found in the irradiated [18O]H2O, but no radionuclide was found in the non-irradiated [18O]H2O neither in the final [18F]FMCH solution with an activity concentration greater than the minimum detectable activity concentration. A total impurity activity<6.2kBq was measured in the irradiated [18O]H2O, whereas a [18F]FMCH radionuclide purity>99.9999998% was estimated. Finally, the decay curve of the irradiated [18O]H2O revealed a very low maximum of 13N activity (<0.03% of 18F) even immediately after the end of bombardment. This study demonstrated the radionuclidic purity of [18F]FMCH according to the EU Pharmacopeia.

14 MeV high intensity cyclotrons: Two projects in progress

A 14 MeV high intensity compact cyclotron, CYCIAE-14, was built at China Institute of Atomic Energy (CIAE). In order to provide high quality proton beams for instant radiopharmaceutical distribution, and to produce a variety of radioactive ion beams taking use of the solid target, CYCIAE-14 adopts an injection system based on the external H- ion source, axial injection, and spiral inflector with a designed high beam intensity, while most PET cyclotrons adopt internal ion source. With the different using for the cyclotron, there are two projects. One project with 200μA/14 MeV can be used for isotope production of 11C, 15O, 13N and 18F. Another project with more than 400μA with 14 MeV can be used for more isotopes produced such as 64Cu, 124I and 99mTc. This paper will introduce the cyclotron of CYCIAE-14 with the two projects, and some experiments finished on the cyclotron will also be given in the paper, for example the 18F and 89Zr production, BNCT test.

Identification of radionuclides in cooling circuit of Cyclone 18/9-HC

In the present work the patterns of relationship of photonic radiation dose rate from Cyclone 18/9HC water cooling system were studied at production of positron-emitting nuclides. Reaction (n, p) was shown to be the main source of activation nuclides in cyclotron cooling water at 18F production, resulting in formation of 16N (T1/2 = 7 s) from 16О. In water targets with high accumulated dose, when beam partially irradiates a target body, proton-induced reactions: 16О(p, α)11С and 18О(p, n)18F take place. Fluoride 18F–, carbonate 11СО32– and hydrocarbonate Н11СО3– anions, formed in proton-induced activation reactions, efficiently precipitate on anion-exchanging resin during water circulation resulting in circuit purification from the named radionuclides. Activation of cooling water does not occur at irradiation of gas targets. Projected annual dose for cyclotron operator from cooling water activation is less than 1 % of annual dose limit for personnel from technogeneous radioactive sources. In order to minimize operator`s accumulated doses it is recommended to decrease the duration of personnel activities at the distance less than 1 meter from heat exchanger during 18F production. At operation of water targets with absorbed dose higher than 2500 μA·h it is desirable to conduct the preventive maintenance of water cooling system not earlier than in half an hour after the end of irradiation and with mandatory dosimetry control. To decrease the activation of impurities it is essential to use only deionized water in cooling circuit. In case of its specific conductivity increase due to corrosion the coolant should be replaced promptly.

Qualitative Analysis of Long-Lived Residual Radioisotopes in 18 MeV Proton Bombarded Enriched Water Target

Residual radioisotope analysis as a result of cyclotron-based 18F production is of paramount importance since it relates to the radiation safety of patients as well as radiation workers. In this investigation, 18-MeV proton beams were employed to irradiate enriched water (H2 18O) target for 18F production while Talys Evaluated Nuclear Data Library (TENDL) 2017 were used to study the origins of the radionuclide impurities. Gamma rays emmitted by the residual radionuclides were detected using a gamma ray spectroscopic system following a month of decay while their origins were analyzed from the TENDL 2017 nuclear cross-section calculations. Experimental results indicated that several long-lived radionuclides such as 109Cd, 57Co, 57Ni, 58Co and 56Co were recorded by the gamma ray spectroscopic system. The long-lived residual radionuclides were presumably due to proton interactions with Havar window and Silver body. Using the TENDL 2017-calculated nuclear cross-sections, it was discovered that several nuclear reactions responsible for the residual radioisotopes include 109Ag(p,n)109Cd which corresponded to the generation of 109Cd radioisotope, 60Ni(p,α)57Co and 58Ni(p,2p)57Co reactions for the formation of 57Co, 58Ni(p,d)57Ni reaction for the production of 57Ni radioisotope, 58Fe(p,n)58Co reaction for the generation of 58Co, and 56Fe(p,n)56Co reaction for the formation of 56Co. This experimental result can be used as a reference for future production of 18F and other radioisotopes should Havar window and silver body are used in the target system.

Characterization of the neutron flux during production of 18F at a medical cyclotron and evaluation of the incidental neutron spectrum for neutron damage studies

The fast neutron spectrum was measured in an irradiation position adjacent to two 18F (fluorine-18) production targets at a medical cyclotron. The neutron spectrum was modeled using MCNP6 and experimentally determined using activation foils. A three-group neutron spectrum was determined using an over-determined least squares fitting method. The MCNP6 model results and measurements of the activation foils were used as input to unfold the neutron spectrum using the STAYSL PNNL code. The neutron spectrum adjacent to the 18F production target was evaluated for use in incidental experiments to evaluate neutron-induced radiolysis of polyurethane and radiation hardness testing of electronics. The fast neutron flux near the 18F target between the energies of 0.4 – 16.5 MeV was 1.8 – 3.0x109 n cm-2s-1. The neutron dose rate in polyurethane at the irradiation position was 2.8 cGy s-1– 5.8 cGys-1. The 1 MeV equivalent neutron flux was 2.4x109 n cm-2s-1 – 4.0x109 n cm-2s-1.

Assessment of the neutron radiation field with activation foils and intermittent irradiations around a PETtrace biomedical cyclotron

This work aimed at assessing the neutron radiation field with activation foils around of the PETtrace biomedical cyclotron. Activation foils of gold, gold covered with cadmium, indium and nickel was used to evaluate the thermal, epithermal and fast neutron contributions, respectively. The irradiations of the activation foils were performed using the intermittent irradiation method to conciliate the measurements with the routine 18F production. The evaluated points showed the contributions of the thermal, epithermal and fast neutrons due to interaction with the vault room, cyclotron accelerator and main cyclotron components.

Formation of 107Cd radionuclide impurities during 18F production

Cd isotopes (107Cd and 109Cd) are generated from the silver target body during the bombardment of [18O]water in the routine production of 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) for PET (Positron Emission Tomography) diagnosis. Cadmium isotopes contribute significantly to the total activity of generated impurities and, due to being potentially radiotoxic to living organisms, they should be effectively reduced from FDG to prevent accidental injection of even small concentrations into patients. Purification of the final [18F]FDG can be based on a set of columns, fulfilling various functions in the cleaning process. To assess cadmium impurities and the efficiency of the purification process, a low background gamma spectrometry system with high resolution has been applied.Even activity of 3.5 kBq and 290 kBq has been measured on QMA (Sep-Pak Light Accell Plus QMA) columns for 109Cd and 107Cd isotopes, respectively. 107Cd activity in the five column set was higher than that of 109Cd. The rate of 18F production process was about 1 GBq/min, while that of 107Cd and 109Cd radionuclides was about 4.2 kBq/min and 50 Bq/min respectively.The same purification efficiency of both isotopes has been obtained at each step of the process. The production rate of 107Cd and 109Cd radionuclides was insignificant compared to the 18F production rate. Therefore [18F]FDG final product for use in injections before PET diagnostics was efficiently purified from cadmium radionuclide impurities.

OA203] Assessment of radiation exposure in a newly formed nuclear medicine department

Purpose In an oncology nuclear medicine department, radioisotopes are not only used for tumor detecting, staging, evaluation of therapy response but also for therapeutic purposes. This study documents the radiation exposure of departmental staff, related to cyclotron operation and service during the production and injection of 18F radiopharmaceuticals for PET/CT examination. In addition, it investigates exposure in a multiple holding tank system used for the storage of 131I waste generated from patients undergoing thyroid therapy, in order to optimize environmental protection procedures. Methods Measurements for the dose rates of neutrons and photons in the room of ABT-BG-75 self-shielded mini-cyclotron were recorded during bombardment for 18F-FDG production using a neutron detector and a scintillation dosimeter. The correlation between the duration of bombardment and required time to reach a dose rate equal to background level was investigated. An electronic dosimeter was used to record staff exposure for 18F production, dispensing, administration and imaging using PET-CT. Finally, the decay rate of 131I waste was measured using a dose rate meter positioned in the decay tank system of the radioactive iodine isolation ward. Results The time required for the cyclotron room to reach background level following completion of bombardment (3 × 50 min each) was approximately 2 h. The dose rate from neutrons was found to be negligible and from photons was less than 7.5 μ Sv/h. Therefore, personnel can safely enter the room during bombardment. The staff mean whole-body dose per 18F-administered patient was 1–2 μ Sv, depending on patient condition. The values obtained from the 131I radioactive waste stored in a delay tank system were comparable with theoretical values. Conclusion This study is useful for optimizing radiation exposure in an oncology nuclear medicine department. It is shown that during 18F production exposure is mostly attributed to photons. The level of the dose permits staff entry into the cyclotron room. Staff responsible for administration received 1–2 μ Sv per 18F-patient, considered to be on the lower end of the acceptable limit for a radiation worker. The study also documents the decay rate of 131I waste over the period which the suggested activity level for release in the environment is reached.

Current status and research activity at the INRNE cyclotron laboratory

A review and update on the status of the Cyclotron Physics Laboratory at the Institute for Nuclear Research and Nuclear Energy as well as related research activity is presented. The main part of the research activities at the Cyclotron Physics Laboratory is directed to simulations for design considerations, for the cyclotron vault for some of the target radioisotopes. In this paper, a review on the simulations, conducted at the laboratory, related to 18F production is included. A model for studying the effect of attenuation and absorption of neutron radiation, emitted by a point source with fixed energy of 14.1 MeV is developed. Preliminary results from this study are shown.

Dependence of 18F Production Yield and Radioactive Impurities on Proton Irradiation Dose

Radiation safety for patients during positron emission tomography (PET) procedures is affected by the amount of radioactive impurities generated during production of fluorine-18 (18F) radionuclide. In this investigation, the dependence of 18F production yield and radioactive impurities on proton irradiation dose is discussed. Enriched water (H2O18) target was bombarded perpendicularly by 11-MeV proton beams at various proton doses. Experimental results indicated that the 18F radioactivity yield and the amount of 56Co and Ag110m radioactive impurities depend strongly on the proton dose. In the proton dose range between 2 μAhr and 20 μAhr, the radioactive impurities increased with increasing proton dose. There was no significant difference in the radioactivity yield of both 56Co and Ag110m impurities at low proton dose between 2 and 10 μAhr. However a huge difference was recorded when the dose was increased above 10 μAhr. The experimental data can be used to predict the amount of impurities generated during 18F production at proton dose of higher than 20 μAhr.

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.

Study of the production yields of 18F, 11C, 13N and 15O positron emitters from plasma-laser proton sources at ELI-Beamlines for labeling of PET radiopharmaceuticals

The development of novel compact PET radionuclide production systems is of great interest to promote the diffusion of PET diagnostics, especially in view of the continuous development of microfluidics labeling approaches. We studied the feasibility to produce clinically-relevant amounts of PET isotopes by means of laser-accelerated proton sources such that expected at the ELI-Beamlines facility. 18F, 11C, 13N and 15O production yields were calculated through the TALYS software, by taking into account the broad proton spectra expected. With the hypothesized proton fluencies, clinically-relevant amounts of radionuclides can be obtained, suitable to prepare single doses of 18F-, 11C- and 13N-labeled radiopharmaceuticals exploiting fast and efficient microfluidic labeling systems.

Nova nucleosynthesis and production of the radioisotope 18F

Novae are cataclysmic stellar explosions driven by nuclear physics under extreme conditions. An important probe of nova conditions could come from the observation of long- lived radioisotopes such as 18F that are produced during the explosion process. To interpret such observations, however, the rates of reactions creating and destroying 18F need to be determined. A variety of direct and indirect studies have greatly reduced uncertainties in nova 18F production. Recent results are reviewed along with prospects for future progress.

Neutron spectra due 13N production in a PET cyclotron

Monte Carlo and experimental methods have been used to characterize the neutron radiation field around PET (Positron Emission Tomography) cyclotrons. In this work, the Monte Carlo code MCNPX was used to estimate the neutron spectra, the neutron fluence rates and the ambient dose equivalent (H*(10)) in seven locations around a PET cyclotron during 13N production. In order to validate these calculations, H*(10) was measured in three sites and were compared with the calculated doses. All the spectra have two peaks, one above 0.1MeV due to the evaporation neutrons and another in the thermal region due to the room-return effects. Despite the relatively large difference between the measured and calculated H*(10) for one point, the agreement was considered good, compared with that obtained for 18F production in a previous work.

Predicting Induced Activity in the Havar Foils of the 18F Production Targets of a PET Cyclotron and Derived Radiological Risk

Predicting Induced Activity in the Havar Foils of the 18F Production Targets of a PET Cyclotron and Derived Radiological Risk

Testing which is the fitter position sensor for a cyclotron liquid target

The [18F]FDG has 109.7min half-life, there is a period about 6h between the beginning of [18O]H2O irradiation until the PET–CT exam. Any fail in production chain will result in delay to the PET–CT exam. The absence of the position signs from [18O]H2O target valve may result in 18F production loss. Three types of position sensors were tested. After finding the fitter sensor it was possible to reduce the incidence of fails, increasing the reliability in [18F]FDG production chain.