Applied Radiation and Isotopes ] (]]]]) ]]]–]]] Contents lists available at ScienceDirect Applied Radiation and Isotopes journal homepage: www.elsevier.com/locate/apradiso Measurement of long lived radioactive impurities retained in the disposable cassettes on the Tracerlab MX system during the production of [18F]FDG D. Ferguson n, P. Orr, J. Gillanders, G. Corrigan, C. Marshall Regional Medical Physics Service, Belfast Health and Social Care Trust, Belfast, Northern Ireland article info abstract Article history: Using a High- Purity Germanium gamma-ray spectrometer, a number of radioisotopes have been Received 15 December 2010 identified within Tracerlab MX radiochemistry system cassettes used to synthesise [18F]FDG. Twenty Received in revised form radiochemistry cassettes were measured and the average total activity of each radioisotope was 20 May 2011 determined. Using these values and decay correction, the minimum time the cassettes should be left in Accepted 22 May 2011 a decay store before the specific activity falls below 0.4B q/g, the limit for disposal alongside Clinical Waste was found to be 24 months. Keywords: & 2011 Elsevier Ltd. All rights reserved. Cyclotron FDG Waste disposal Radioactive waste 1. Introduction Since 18FÀ is produced by the 18O(p,n)18F reaction, it is neces- sary to remove the 18F-ion from its aqueous environment. On the 18F is the most widely used radionuclide in PET and is GE Tracerlab MX system, which utilises disposable cassettes commonly produced by bombarding 18O enriched water with (supplied by Rotem Industries, Ltd), this is performed using a QMA accelerated protons. It is well established that long lived radio- Sep-Pak column (supplied as a part of ABX reagent kit, Biomedizi- nuclide impurities are generated using this method as a result of nische Forschungsreagenzien GmbH). The 18FÀ ion is retained on the 18 activation of metal atoms in the Havar foil and silver body of the column whilst the [ O]H2O passes through. In theory, the activated Gen II targets used in the GE PETtrace cyclotron [Bowden et al., metal ions should pass through the column and are not retained. The 2009; Marengo et al., 2008; Ito et al., 2006; Gillies et al., 2006; 18F is then eluted from the column with an Acetonitrile solution of Mochizuki et al., 2006; O’Donnell et al., 2004]. Havar foil is a heat Kryptofix and Potassium Carbonate. (Yu, 2006) treatable, cobalt based non-magnetic alloy with a high strength The long lived impurities are removed during synthesis and excellent corrosion resistance. Its nominal composition is enabling the final [18F]FDG product to meet the requirements of cobalt (42.0%), chromium (19.5%), nickel (12.7%), tungsten (2.7%), the pharmacopoeias [BP, 2010; EP, 2010]. However, the long lived molybdenum (2.2), manganese (1.6%), carbon (0.2%) and iron impurities are retained in the disposable cassette used on the (balance) and these metals are the sources for most of the Tracerlab MX radiochemistry system. activated radioisotopes (Havar Technical Data Sheet). The radio- Other authors (Tables 6 and 7) have confirmed the presence of isotopes are generated by interactions between the cyclotron these long lived impurities in both the Havar foil and the target foil and the proton beam as it passes through as well as fluorinated water. The aim of this study was to measure the with secondary neutrons. During the interaction with the protons levels of these long lived impurities in the disposable cassettes, and neutrons, some of the activated radionuclides are knocked and thus the levels of radioactive waste generated during synth- into the 18O enriched water through the process of spallation. esis, to determine the most appropriate method of disposal. The These long lived impurities are then transferred, along with the disposal of cassettes is an issue for any centre producing FDG, 18F water, to the synthesis unit. which applies a single-use cassette chemistry system. Table 1 shows the possible interactions of the incident proton beam, or secondary neutrons, within the Havar foil and silver target body by which the radioactive by-products detected may 2. Material and methods be created. [Ito et al., 2006; Marengo et al., 2008] 2.1. 18F—Fluoride production and [18F]FDG synthesis 18 n Corresponding author. Tel.: þ44 28 90636558; fax: þ44 28 9063 4304. 20 Production runs of F were performed using a PETtrace E-mail address: [email protected] (D. Ferguson). 6 cyclotron (GE Healthcare). Target conditioning was undertaken 0969-8043/$ - see front matter & 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.apradiso.2011.05.028 Please cite this article as: Ferguson, D., et al., Measurement of long lived radioactive impurities retained in the disposable cassettes on the Tracerlab MX system during the production of [18F]FDG. Appl. Radiat. Isotopes (2011), doi:10.1016/j.apradiso.2011.05.028 2 D. Ferguson et al. / Applied Radiation and Isotopes ] (]]]]) ]]]–]]] 16 by filling a single Gen II silver target with water ([ O]H2O) and Each cassette was removed from the Tracerlab MX 48 h after irradiating for 10 min with a 16.5 MeV proton beam at 25 mA. the production of FDG. This was to allow the radioactivity in the Afterwards the same target was filled with enriched water cassettes to decay to a level where it could be safely cut up and 18 ([ O]H2O; Sercon) and irradiated using a proton beam of 40 mA placed in a 1 lt tub. The cut up cassette was then stored for a for 2 h. The fluoride produced was delivered to a hot cell further week to allow the activity to fall to a level that could be (Gravatom) where synthesis of FDG was performed using a measured by the gamma-ray spectrometry system without large Tracerlab MX (GE Healthcare) radiochemistry system along with dead-time effects. reagents, solvents and columns supplied by ABX (Advanced Biochemical Compounds, Germany). After the main production 2.2. Gamma-ray spectrometry and analysis and delivery of FDG to the hot cell, the target was filled with 18 18 water [ O]H2O to remove any residual F, which could poten- To detect impurities in the cassette, a gamma-ray spectro- tially cause contamination and corrosion of the target. The whole metry system consisting of an ORTECs GMX Series High-Purity procedure was finished by drying the target for 15 min to ensure Germanium (HPGe) Coaxial Photon Detector operated by Gam- that the target was ready for the next production. maVisions-32 v6.08 software was used. The resolution (FWHM) of this system is 0.73 keV at 5.9 keV and 1.8 keV resolution at Table 1 1330 keV with a relative efficiency of 27%. The system has been Possible nuclear reactions that create detected radioactive impurities. calibrated for a range of uniform geometries, including a 1 lt tub, using a number of aliquots of CERCA LEA 9ML01ELMG05 multi- Radionuclide Havar foil Silver target gamma reference source containing 241Am, 109Cd, 57Co, 139Ce, 113Sn, 85Sr, 137Cs, 88Y and 60Co as well as a 152Eu point source from 51Cr 54Fe(n,a)51Cr 50Cr(n,g)51Cr Amersham for energy calibration. The operational range of the 52Cr(n,2n)51Cr detector was set from 10–2000 keV. 52Mn 52Cr(p,n)52Mn Each 1 lt tub was placed directly on the detector and a 54Mn 54Cr(p,n)54Mn 54 54 spectrum captured for 8 h, which was analysed using the Gam- Fe(n,p) Mn s 55Mn(n,2n)54Mn maVision -32 application, with the measured activity of each 56Co 56Fe(p,n)56Co detected radioisotope decay corrected back to the time of produc- 57Co 57Fe(p,n)57Co tion. The GammaVision software will only decay correct the 58 57 Ni(n,pn) Co activity measured for radioisotopes if less than 12 half-lives have 58Ni(p,2p)57Co elapsed. For this reason, each cassette was analysed within 30 60Ni(p,a)57Co 58Co 58Fe(p,n)58Co days of production to ensure that as many of the short-lived 58Ni(n,p)58Co radioisotopes could still be decay corrected while taking into 59Co(n,2n)58Co account the time needed for the cassette to be cool enough to 59 58 Co(p,pn) Co prevent dead-time effects. Nuclear data for the photon energies 57Ni 58Ni(p,d)57Ni 95Tc/95mTc 95Mo(p,n)95mTc and g-ray emission probabilities of the radioisotopes in the 96Mo(p,2n)95mTc GammaVision radionuclide library were obtained from the Eval- 96Tc 96Mo(p,n)96Tc uated Nuclear Structure Data File database (ENSDF). 97Mo(p,2n)96Tc 109Cd 109Ag(p,ng)109Cd 182Re 182W(p,n)182Re 184W(p,3ng)183Re 3. Results 183Re 183W(p,n)183Re 184Re 184W(p,n)184Re Fig. 1 shows a typical g-ray spectrum obtained with the GMX- 186Re 184W(p,n)186Re HPGe detector, labelled with the identified isotopic peaks. Eleven Fig. 1. Spectrum showing radioisotope photon peaks. Please cite this article as: Ferguson, D., et al., Measurement of long lived radioactive impurities retained in the disposable cassettes on the Tracerlab MX system during the production of [18F]FDG. Appl. Radiat. Isotopes (2011), doi:10.1016/j.apradiso.2011.05.028 D. Ferguson et al. / Applied Radiation and Isotopes ] (]]]]) ]]]–]]] 3 Table 2 Distribution of gamma-emitting radionuclide impurities in the FDG synthesis cassettes. Radionuclide Half life (d) Primary c [keV] Primary c abundance [%] Average activity (Mean7SEM) [Bq] Median activity [Bq] Range [Bq] n¼20 51Cr 27.7 320 9.86 373.0781.6 209.2 87.4–1565 52Mn 5.59 1434 100.00 194.0761.5 48.8 0–929.1 54Mn 312 835 99.98 3.070.7 2.3 0–9.1 56Co 77.2 847 99.93 206.6730.3 144.5 61.6–519.4 57Co 272 122 85.60 37.175.1 27.5 11.2–75.2 58Co 70.9 811 99.45 260.1738.2 182.6 64.4–662.5 95mTc 61.0 204 61.92 58.479.9 48.6 6.2–180.2 96Tc 4.28 778 99.76 846.57147.9 755.5 0–2393.8 109Cd 461 88 3.63 81.8712.3 58.1 20–180.5 182Re 2.67 229 26.00 11.276.3 0.0 0–86.6 183Re 70.0 162 23.36 22.475.1 17.0 0–84.3 Table 3 Table 4 Total activity in the FDG cassettes at the end of bombardment (EOB).