Experimental study of excitation functions for the deuteron induced reactions 64Zn(d,2p)64Cu and 64Zn(d,alphan)61Cu using the stacked-foil technique.

There is considerable, and growing, interest in the 64Cu radioisotope for application in Nuclear Medicine for PET imaging and targeted radiotherapy of tumours. We are investigating the cyclotron production of this isotope by way of deuteron bombardment of enriched 64Zn target material. In this study, experimental excitation functions for both the 64Zn(d,2p)64Cu and 64Zn(d,alphan)61Cu reactions up to 18.2 MeV deuteron energy have been measured using the stacked-foil technique. The deuteron energies in the various foils were calculated with the SRIM 2003 code and gamma-ray spectrometry was used to measure the activities of the various radioisotopes produced. Monitor foils were used to determine the deuteron beam current on the target stack. Theoretical excitation functions, calculated both with the Empire II code and with an updated version of the Alice code, were compared with the experimental results and a reasonable agreement was found. The experimental work was performed at the MC40 Cyclotron at the European Commission's Joint Research Centre at Ispra, Italy.     

18FDG SPECT to assess myocardial viability: initial experience at a hospital remote from a cyclotron

18F-Fluorodeoxyglucose positron emission tomography (18FDG PET) is the recognized gold standard for the assessment of myocardial viability, but is not widely available in the UK. FDG imaging on a gamma camera with high-energy collimators (FDG SPECT) has been shown to have an accuracy comparable with that of FDG PET for the assessment of myocardial viability. This study was performed to assess the feasibility of introducing FDG SPECT for myocardial viability at a hospital a considerable distance away from a cyclotron (200 miles). Twenty-three patients, who were being actively considered for revascularization but had demonstrated fixed defects on stress/rest with nitrate tetrofosmin imaging, underwent FDG SPECT. Image quality was acceptable in all patients. Nine out of the 23 patients with defects classed as fixed on tetrofosmin imaging demonstrated viability on FDG SPECT. Six of these nine patients, reported to have some viable myocardium on FDG SPECT, underwent revascularization as a result. This study has demonstrated that FDG SPECT is feasible at a site some distance from a cyclotron.     

Excitation functions of natZn(p,x) nuclear reactions with proton beam energy below 18 MeV

We measured the excitation functions of ^natZn (p,x) reactions up to 17.6 MeV, using the stacked-foils activation technique. High-purity natural zinc (and copper) foils were irradiated with proton beams generated by an 18 MeV isochronous cyclotron. Activated foils were measured using high-purity Ge gamma spectroscopy to quantify the radionuclides ⁶¹Cu, ⁶⁶Ga, ⁶⁷Ga, and ⁶⁵Zn produced from the reactions. Thick-target integral yields were also deduced from the measured excitation functions of the produced radioisotopes. These results were compared with the published literature and were found to be in good agreement with most reports, particularly those most recently compiled.     

18F]-labeled 3-deoxy-3-fluoro-D-glucose: synthesis and preliminary biodistribution data.

A cyclotron target system for the production of anhydrous [18F] fluoride ion has been developed and used for the synthesis of carrier-free [18F]-3-deoxy-3fluoro-D-glucose (3-FDG). The synthesis is sufficiently rapid and efficient to allow production of usable amounts of 3-FDG with a 6-MeV cyclotron. Preliminary animal studies show that 3-FDG is in fact a glucose analog.     

Monte Carlo calculation of epithermal neutron resonance self-shielding factors in foils of different materials

Epithermal neutron resonance self-shielding factors in foils of materials used as activation detectors or as targets for radionuclide production have been calculated using the MCNP code. Two irradiation conditions have been considered: (a) foils immersed into an isotropic neutron flux and (b) foils submitted to a collimated neutron beam. The self-shielding factors, G_res(t), for gold, indium, manganese and cobalt have been compared with available published values. The self-shielding factor depends on various physical and nuclear parameters. However, it is shown that for the isotropic case and for high absorber elements submitted to a collimated beam, a dimensionless variable could be adopted that describes the self-shielding factors of different materials by quasi “universal curves”. G_res(t) for the collimated beam are always higher than those for the isotropic case.     

Production of ultra thin silicon foils

Ultra thin silicon foils with thicknesses below 100 nm and large diameters have been produced. Foils with a thickness of 50-60 nm have been used as supporting foils for zone plates and as vacuum windows withstanding a pressure difference of 1 atm.     

Initial and subsequent approach for the synthesis of 18FDG

2-deoxy-2-[18F] fluoro-D-glucose (18FDG) was developed in 1976 in a collaboration between scientists at the National Institutes of Health, the University of Pennsylvania, and Brookhaven National Laboratory. It was developed for the specific purpose of mapping brain glucose metabolism in living humans, thereby serving as a tool in the basic human neurosciences. With 18FDG it was possible for the first time to measure regional glucose metabolism in the living human brain. Around the same time, the use of 18FDG for studies of myocardial metabolism and as a tracer for tumor metabolism were reported. After the first synthesis of 18FDG via an electrophilic fluorination with 18F gas (produced via the 20Ne(d,alpha)18F reaction), small volume enriched water targets were developed that made it possible to produce large quantities of [18F]fluoride ion via the high-yield 18(p,n)18F reaction. This was followed by a major milestone, the development of a nucleophilic fluorination method that produced 18FDG in very high yield. These advances and the remarkable properties of 18FDG have largely overcome the limitations of the 110-minute half-life of 18F so that 18FDG is now available to most regions of the United States from a number of central production sites. This avoids the need for an on-site cyclotron and chemistry laboratory and has opened up the use of 18FDG to institutions that have a positron emission tomography (PET) scanner (or other imaging device) but no cyclotron or chemistry infrastructure. Currently, 18FDG is used by many hospitals as an off the shelf radiopharmaceutical for clinical diagnosis in heart disease, seizure disorders, and oncology, the area of most rapid growth. However, it remains an important tool in human neuroscience and in drug research and development.     

Tantalum-178--a short-lived nuclide for nuclear medicine: production of the parent W-178

The physical decay characteristics of the short-lived radionuclide Ta-178 (half-life 9.3 min) appear to be suitable for use in conjunction with low-energy detection systems such as the multiwire proportional camera. This camera is inefficient for emissions with energies greater than 100 keV. The gamma-ray spectrum of Ta-178 is dominated by the characteristic hafnium x-rays (55--65 keV), emitted as a result of electron-capture decay. The parent nuclide, W-178 (half-life 21.7 d), was produced in the Michigan State University cyclotron by proton bombardment of stacked natural tantalum-foil targets. Optimum production was found to occur with an incident proton energy of 34 MeV at an effective activity of 1.1 mCi/muA-hr per MeV of target thickness. Tungsten-178 was chemically separated from the Ta foils with a yield of 98%.     

Radioactivity measurement of 18F in 16 ml vials for calibration of radionuclide calibrators

Fluorine-18 is obtained through the reaction (18)O(p, n)(18)F using a cyclotron that is situated in a hospital in Jakarta. Standardization of the (18)F solution is performed by gamma spectrometry using calibration sources of (152)Eu, (60)Co and (137)Cs that have traceability to the International System of units (SI). The activities in the 16 ml vials that were used for calibrating the radionuclide calibrators were between 1 and 2 GBq, with expanded uncertainties of 3.8%. The expanded uncertainty, at a coverage factor of k=2, on the derived calibration factor for the radionuclide calibrator was 6.6%.     

Gallium-68: a new trend in PET radiopharmacy

The most common PET radioisotopes, both in the literature and in clinical practice, are the cyclotron produced 11C and 18F, giving rise to tracers with minimal chemical changes with respect to the original biological molecule. However, the short half-life of these two radioisotopes and the relatively complex chemistry of their incorporation into the molecules of interest limits the number of molecules that really can be labelled in a suitable length of time. 68Ga is a positron emitter, produced by a 68Ge/68Ga generator rending the production of its radiopharmaceuticals independent of an onsite cyclotron. This paper covers the main aspects of the Ga3+ coordination chemistry together with the state of art of its radiopharmacy.     

A simple method for determining the activity of large-area beta sources constructed from anodized aluminum foils

A simple method has been developed for determining the activity of large-area beta reference sources in anodized aluminum foils. It is based on the modeling of the transmission of beta rays through thin foils in planar geometry using Monte Carlo simulation. The method was checked experimentally and measurement results show that the activity of large-area beta reference sources in anodized aluminum foils can be measured with standard uncertainties smaller than the limit of 10% required by ISO 8769.     

A grid-mounted niobium body target for the production of reactive [18F]fluoride.

A small-volume grid-supported niobium target was constructed for the production of [18F]-fluoride on a CTI RDS 112 cyclotron. The inert properties of niobium metal have proven compatible with the superheated environment generated during proton irradiation. A grid support, constructed from aluminum, provides the necessary heat removal for high-power irradiations. The niobium and gird combination supplies reactive fluoride over an extended target lifetime.     

Niobium sputtered Havar foils for the high-power production of reactive [18F]fluoride by proton irradiation of [18O]H2O targets.

Niobium sputtered Havar entrance foils were used for the production of reactive [(18)F]fluoride by proton irradiation of [(18)O]H(2)O targets under pressurized conditions. The synthesis yield in the routine production of 2-[(18)F]fluoro-2-deoxy-glucose (FDG) was used as an indicative parameter of the reactivity of (18)F. The yield of FDG obtained with (18)F produced in a target with Havar foil was used as a baseline. No statistically significant difference was found in the saturated yields of (18)F when using Havar or Havar-Nb sputtered entrance foils. However, the amount of long-lived radionuclidic impurities decreased more than 10-fold using the Havar-Nb entrance foil. The average decay corrected synthesis yield of FDG, evaluated over a period of more than 2 years, was found to be approximately 5% higher when using a Havar-Nb entrance foil and a marked improvement on the FDG yield consistency was noted. In addition, the frequency of target rebuilding was greatly diminished when using the Nb sputtered entrance foil.     

GE PETtrace cyclotron as a neutron source for boron neutron capture therapy.

This paper discusses the use of a General Electric PETtrace cyclotron as a neutron source for boron neutron capture therapy. In particular, the standard PETtrace (18)O target is considered. The resulting dose from the neutrons emitted from the target is evaluated using the Monte Carlo radiation transport code MCNP at different depths in a brain phantom. MCNP-simulated results are presented at 1, 2, 3, 4, 5, 6, 7, and 8 cm depth inside this brain phantom. Results showed that using a PETtrace cyclotron in the current configuration allows treating tumors at a depth of up to 4 cm with reasonable treatment times. Further increase of a beam current should significantly improve the treatment time and allow treating tumors at greater depths.     

医用回旋加速器及正电子核素生产

PET(正电子发射体层)显像是利用解剖形态方式对体内各种生物化学过程如代谢和受体功能改变等进行评价和定量观测的核医学技术,PET的发展在一定程度上取决于正电子显像剂的研制与应用。PET所采用的正电子显像剂主要是用由回旋加速器生产的正电子核素-11C、13N、15I、18F等标记。因此,了解并掌握医用回旋加速器的基本组成和工作原理,选择适当的正电子核素及其标记前体,对正电子显像剂的常规生产和研究开发有重要的指导意义。主要介绍了回旋加速器的操作原理、医用回旋加速器的类型和正电子核素及其标记前体的生产。     

Synthesis and evaluation of fluorine-18 21-fluoroprednisone as a potential ligand for neuro-PET studies

No-carrier-added fluorine-18-labeled fluoroprednisone ([18F]21-fluoroprednisone) was synthesized by tosylate displacement in 2%-8% radiochemical yield in 80 min end of cyclotron bombardment (EOB), and its metabolism and distribution were investigated. After intravenous administration to rats, [18F]21-fluoroprednisone was rapidly cleared from the blood and biotransformed into [18F]20-dihydro-21-fluoroprednisone. The suitability of [18F]21-fluorocorticoids for receptor imaging in humans with positron emitting tomography will depend on the synthesis of compounds with high binding affinity and low rate of carbonyl reduction at C-20.     

Radionuclide impurities in proton-irradiated [18O]H2O for the production of 18F−: Activities and distribution in the [18F]FDG synthesis process

Proton- and neutron-induced activation products in the components of a high-pressure [¹⁸O]H₂O target vessel used for the production of ¹⁸F⁻ in a medical cyclotron have been identified using high resolution gamma spectrometry. The activities leached from the target vessel into the [¹⁸O]H₂O during irradiation, and the distribution of the identified radionuclide impurities in the various cartridges and solutions used in the [¹⁸F]FDG synthesis process have been measured and are discussed from the perspective of waste disposal. The results indicate that, at the energies and beam currents employed, only a few, relatively short-lived radionuclides are present in the irradiated [¹⁸O]H₂O, and that the activities involved (<10 kBq in each case) are well below typical exemption limits. Activities of beta-emitting ³H in irradiated [¹⁸O]H₂O, produced via the ¹⁸O(p,³H)¹⁶O reaction, have also been determined using liquid scintillation spectrometry. Measured activity concentrations, in the range 150–180 kBq g⁻¹, are consistent with those reported by other workers. Analyses of the synthesised [¹⁸F]FDG confirm the radiochemical purity of the product, both for ³H and for gamma-emitting radionuclides in the energy range 25–1650 keV.     

A solid target system with remote handling of irradiated targets for PET cyclotrons

A solid target system was developed for a PET cyclotron. The system is compatible with many different target materials in the form of foils and electroplated/sputtered targets which makes it useful for production of a wide variety of different PET radionuclides. The target material is manually loaded into the system. Remote handling of irradiated target material is managed with a pneumatic piston and a vacuum technique which allows the targets to be dropped into a shielded transport container. To test the target performance, proton irradiations (12.8 MeV, 45 μA) of monoisotopic yttrium foils (0.64 mm, direct water cooling) were performed to produce ⁸⁹Zr. The yields were 2200±200 MBq (1 h, n=13) and 6300±65 MBq (3 h, n=3).     

Diagnostic assessment to estimate and minimize neutron dose rates received by occupationally exposed individuals at cyclotron facilities

Since 2003, radiopharmaceuticals for medical diagnostic purposes have been produced at the Instituto de Engenharia Nuclear, in Brazil, using two cyclotron accelerators – CV-28 and RDS111. As a result of the ever increasing production, a diagnostic assessment to reduce neutron dose rates received by occupationally exposed individuals during irradiation processes has been developed. The purpose of this work is to present this assessment, which is currently being applied to both the Fluorine and Iodine targets of CV-28 and RDS111 cyclotron accelerators.     

Separation of iron-55 from manganese cyclotron target material on a 2% cross-linked anion exchanger in hydrochloric acid

A simple method is presented for the separation of iron-55 from manganese cyclotron targets. Anion exchange chromatography with 9.0 M hydrochloric acid on a 2% cross-linked resin provides separation not only from large amounts of managanese but also from copper and zinc impurities. Separations are sharp and quantitative and less than 1 μg of manganese remains with the iron-55 when 2 g have been present originally.