J Radioanal Nucl Chem (2012) 293:45–49 DOI 10.1007/s10967-012-1772-4
Production of cationic 198Au3+ and nonionic for radionuclide therapy applications via the natAu(n,c)198Au reaction Mahdi Sadeghi • Hamidreza Jabal-Ameli Seyed J. Ahmadi • Sodeh S. Sadjadi • Mohamadreza K. Bakht
198
Au0
•
Received: 23 October 2011 / Published online: 10 April 2012 Ó Akade´miai Kiado´, Budapest, Hungary 2012
Abstract 198Au (bmax = 0.96 MeV (98.6 %), cmax = 0.412 MeV (95.5 %) and T1/2 = 2.7 days) is a radionuclide with very appealing characteristics. 198Au has been widely used to treat the uterus, bladder, cervix, prostate, melanoma, breast, skin and other cancers. In the present study, cationic 198Au?3 and nonionic 198Au0 are prepared following thermal neutron irradiation of commercially available natural gold compounds in Tehran Research Reactor via the natAu(n,c)198Au reaction. The prospects in the production of pure 198Au0 and 198Au?3 for radionuclide therapy are discussed and effect of reduction on the activity of radioactive gold is evaluated. Au0 particles were synthesized via NaBH4 reduction of aqueous solutions of hydrogen tetrachloroaurate trihydrate. Then two quartz tubes were charged with cationic 198Au3? and nonionic 198 Au0. After irradiation by thermal neutrons, the samples were analyzed for a period of 1 month by liquid scintillation counter and high purity germanium detector. As a M. Sadeghi (&) Agricultural, Medical and Industrial Research School, Nuclear Science and Technology Research Institute, P.O. Box 31485/498, Karaj, Tehran, Iran e-mail:
[email protected] H. Jabal-Ameli Department of Medical Radiation Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran S. J. Ahmadi S. S. Sadjadi Jaber Ibne Hayan Research Laboratories, Nuclear Science and Technology Research Institute, P.O. Box 11365-8486, Tehran, Iran M. K. Bakht Young Researchers Club, Science and Research Branch, Islamic Azad University, Tehran, Iran
result, natAu3? reduction process had no significant effect on the activity of the 198Au sample. In conclusions, natural gold thermal neutron activation cross section is reasonably high for medical application. Keywords 198Au Radioisotope activity Reactor production Reduction
Introduction Application of radioisotopes is an important subject in the pharmaceutical sciences [1]. Targeted radiotherapy with radionuclides has several advantages over external beam radiotherapy, including the possibility of selectively delivering higher doses to the tumor and treating multiple metastases [2]. Recently, radionuclide therapy is based almost exclusively on energetic b--particle emitting isotopes. Moreover, an ideal therapeutic radionuclide would be a b--emitter with appropriate c energy to facilitate real-time external imaging [2, 3]. Gold-198 is a radionuclide with very interesting therapeutically features, with beta major emission of 0.96 MeV (98.6 %) and 0.412 MeV (95.5 %) of gamma radiation [4, 5]. Natural gold has only one isotope, 197 Au. Its thermal neutron activation cross section is fairly high (r = 98.8b). The activation product 198Au has a short half-life (T = 2.7 days) and emits b- and c-rays suitable for detection. 198Au with a high specific activity can be easily produced by irradiation of gold in a nuclear reactor [6, 7]. 198 Au has been used to treat cancers for years in brachytherapy, generally as individual seeds in permanent implant forms [8, 9]. Moreover, 198Au is shown a predominantly local effect when is inserted into the peritoneal cavity. Nevertheless, Intra tumor injection of 198Au it delivers very large quantities of ionizing radiation inside a
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tumor without over dose in the surrounding normal tissues [10, 11]. Furthermore, 198Au has been widely used to treat the following cancers: uterus, bladder, cervix, prostate, melanoma, breast, skin and other cancers [12–17]. Khan et al. [15] described the fabrication of poly ({198Au}) radioactive gold-dendrimer composite nanodevices for targeted radiopharmaceutical dose delivery to tumors in vivo. Irradiation of aqueous solutions of 197Au containing poly (amidoamine) dendrimer tetrachloroaurate salts or {197Au0} gold-dendrimer nanocomposites in a nuclear reactor resulted in the formation of positively charged and soluble poly{198Au0} radioactive composite nanodevices (CNDs). It is also noteworthy that the pioneering efforts by Professor Katti has demonstrated the enormous potential of radioactive gold nanoparticles in cancer therapy [18]. Most of the reactor-produced radioisotopes such as 198 Au are products of the (n,c) reaction. [19, 20]. The radiochemical data are of considerable practical importance, especially in production of medical radionuclides and radiation therapy [1, 21]. The nuclear reaction models are commonly needed to provide educated guesses of the reaction cross-sections. In this work, the reported experimental data and the evaluated excitation functions based on nuclear model calculations via recent nuclear codes from various databases were compared for the natAu(n,c)198Au reaction to evaluate accuracy of the theoretical calculations. In addition, the impact of the reduction process on the activity of the 198Au sample was evaluated. 198Au samples were prepped following thermal neutron irradiation of commercially available natural gold compounds in Tehran Research Reactor (TRR).
Materials and methods All chemicals used were of AR/GR grade from reputed chemical manufacturers. Tetrachloroauric (III) acid trihyTM drate 99.5 % (HAuCl43H2O) was purchased of Merck and used for neutron irradiations. Preparation of the targets for irradiation Nonionic Au0 particles were synthesized via NaBH4 reduction of aqueous solutions of hydrogen tetrachloroaurate trihydrate (HAuCl43H2O). 0.31 ml of a 0.03 M hydrogen tetrachloroaurate trihydrate solution was added to 1.25 ml of a 0.1 M sodium borohydride solution. This mixture was stirred for 30 min at 0 °C in air. Then two quartz tubes were charged with 0.5 ml of this solution (Au0 particles) and 0.5 ml of a 0.06 M hydrogen tetrachloroaurate trihydrate solution (Au?3 particles). It should be noted that the masses of gold in two samples were equal
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(1.12 mg). Lastly, quartz tubes were flame sealed under vacuum and cold welded in aluminum can. Neutron irradiation of the targets 198
Au was produced by thermal neutron bombardment of Au via a (n,c) reaction in TRR at a flux of 2.53 9 1013 n cm-2 s-1 for 30 min. Then the can was opened inside a lead-shielded plant.
nat
Processing in hot cell After irradiation, each sample was diluted to 50 ml, and then analyzed by liquid scintillation counter (LSC) and high purity germanium detector (HPGe). Radionuclide (RN) purity of 198Au samples was determined by high resolution gamma ray spectrometry using an HPGe detecTM tor (Silena International 2000) coupled to a multi channel analyzer (MCA). The counting of beta emissions of 198Au was carried out by using liquid scintillation counter TM (Wallac 1220 Quantulus ) with two dual MCAs. Calculation of the cross section The TALYS program simulates the nuclear reactions that involve gammas, neutrons, protons, deuterons, tritons, 3He and a-particles in the incident energy range from 1 keV to 200 MeV for target nuclides of mass 12 and heavier. TALYS provides estimates of all the open reaction channels involving the above-mentioned light particles and fission. TALYS uses by default in the phenomenological optical model parameterizations for neutrons and protons on a nucleus-by-nucleus basis to obtain the transmission coefficients and the reaction cross sections. If the potential is not available, TALYS automatically uses a global optical model. The energy dependence of the various potential depths is in agreement with those resulting from microscopic optical model studies [1, 22]. In addition, TALYSbased evaluated nuclear data library (TENDL) is a nuclear data library that provides the output of the TALYS nuclear model code system for direct use in both basic physics and applications with some modifications. The third version is TENDL-2010, which is based on both the default and the adjusted TALYS calculations and the data from other sources [23]. Furthermore, the European Activation File (EAF) is the collection of nuclear data that is required to carry out inventory calculations of materials that have been activated following exposure to neutrons or charged particles. The EAF-2010 library contains 66,256 excitation functions involving 816 different targets from 1H to 257Fm, atomic numbers 1–100, in the energy range 10-5 Ev to 60 MeV. The 3,660,206 lines that make up the point-wise file are
198
Au3? and nonionic
198
Au0 for radionuclide therapy applications
then processed into numerous group-wise files with different micro-flux weighting spectra to meet various user needs. Uniquely, an uncertainty file is also provided that quantifies the degree of confidence placed on the data for each reaction channel [24]. Calculation of the activity When a target is under irradiation in a reactor, the activation per second can be represented by: dN 0 ¼ nvdact NT dt
dN 0 ¼ nvdact NT kN 0 dt
ð2Þ
where kN’ indicates the decay rate of product nucleus. Equation 2 can be solved to determine the value of radioactive atoms at time ‘t’, as follows: S¼
TENDL-2010 EAF-2010 Experimental data
1.E+0
1.E-5
Thermal neutrons energy range
1.E-10
ð1Þ
where NT is the total number of atoms present in target, nv is neutron flux = u, ract is activation cross section, N is the number of activated atoms [19]. Equation 1 considers the neutron flux to be isotropic. In case the neutrons are not mono-energetic and if a velocity distribution exists, then the average value of the flux is to be considered. Since the product radioisotope starts decaying with its own half-life, once production starts Eq. 1 representing net growth rate of active atoms can be written as:
0:6du 1 ekt Bq=g A
ð3Þ
where r is the neutron activation cross section leading to the production of radioisotope of interest in barn, u is the flux in n cm-2 s-1, t is the time of irradiation, k is the decay constant and A is atomic weight of target element. Equation 3 clearly shows that growth of activity in a target under irradiation is exponential in nature and reaches a saturation value limited by the neutron flux in the reactor [19, 20].
47
1.E+5
Cross section (b)
Production of cationic
1.E-5
1.E+0
Incident neutron energy (MeV)
Fig. 1 Comparison between the experimental data and the evaluated excitation function form TENDL [23] and EAF [24] databases for the nat Au(n,c)198Au reaction. The experimental values have been taken from EXFOR [25]
values have been taken from experimental nuclear reaction data (EXFOR) [25]. At thermal neutrons energy range, there is a good agreement between the reported experimental data and the evaluated excitation functions based on nuclear model calculations via recent nuclear codes form various databases. Further, at this energy range, excitation function from reaches the maximum cross section value of about 100b. Therefore, natural gold thermal neutron activation cross section is reasonably high for medical application. Theoretical calculation of the activity According to Eq. 3 of activity in the targets under irradiation of neutron flux in TRR was calculated. Table 1 shows the theoretical activity of 198Au0 and 198Au3? samples containing 1.12 mg of gold. Accordingly, 198Au0 activity is slightly less than 198Au3? owing to a little more molecular mass target. Cationic
198
Au3? production
198
Results and discussion Excitation function of the
nat
Au(n,c)198Au reaction
Natural gold can be used to produce 198Au via thermal neutron irradiation. On the one hand, natAu(n,c)198Au process is determined as a profitable reaction since natural abundance of 197Au is 100 %; therefore, the target of this reaction doesn’t need enriching. Figure 1 shows comparison between the experimental data and the evaluated excitation function form TENDL [23] and EAF [24] databases for the natAu(n,c)198Au reaction. The experimental
Au radioactivity was estimated by its characteristic 411.8 keV photopeak (Fig. 2). In addition, mononuclidic existence of 197Au produced 198Au without other activation product of gold. The counting of gamma emissions of 198Au by HPGe reached to 41,400 count per second (CPS) and 32,115 CPS after 6 and 24 h, respectively. Besides, based
Table 1 The theoretical activity of Au0 and Au3? samples containing 1.12 mg of gold Sample 198
?3
198
0
Au Au
Activity (after 6 h) Bq
Activity (after 24 h) Bq
7
2.146 9 107
7
1.953 9 107
2.598 9 10 2.364 9 10
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M. Sadeghi et al.
Fig. 2 Gamma spectrum of 198 Au recorded using HPGe– MCA system after 6 h
(411.8, 41400) 40000
Count per channel
35000 30000 25000 20000 15000 10000 5000
223.8
661.9
443.8
880.9
1318.9
1099.9
1537.9
1756.9
1976
Channel (keV) Fig. 3 The liquid scintillation spectrum of 198Au
30000
Count per minute
28000 23000 18000 13000 8000 3000
100
200
300
400
500
600
700
800
900
1000
Channel number
on the LSC spectrums of 198Au, activity of beta radiation of the samples were calculated (Fig. 3). The counting of beta emissions of 198Au3? by LSC reached to maximum of 27,000 count per minute (CPM) and 23,800 CPM after 6 and 24 h, respectively. In order to calculate total activity of the samples, obtained data by HPGe and LSC were used. As can be seen on Table 2, 1.12 mg of HAuCl4 irradiated for 30 min at a thermal neutron flux of 2.53 9 1013 n cm-2 s-1 produced 2.54 9 107 Bq 198Au3?. Nonionic
198
Au0 production
Similarly, 198Au radioactivity was estimated by its characteristic 411.8 keV photopeak. In addition, mononuclidic existence of 197Au produced 198Au without other activation product of gold. The counting of gamma emissions of 198 Au0 by HPGe reached to 37,500 and 29,100 CPS after 6 and 24 h, respectively. Besides, based on the LSC spectrums of 198Au, activity of beta radiation of the samples were calculated. The counting of beta emissions of 198Au0 by LSC reached to maximum of 25,300 and 22,200 CPM after 6 and 24 h, respectively. In order to calculate total activity of the samples, obtained data by HPGe and LSC were used. As can be seen on Table 2, 1.12 mg of Au0
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Table 2 The experimental measurement of the activity of 1.12 mg of irradiated samples for 30 min at a thermal neutron flux of 2.53 9 1013 n cm-2 s-1 Sample
Activity (after 6 h) Bq
Activity (after 24 h) Bq
198
2.54 9 107
2.14 9 107
7
1.94 9 107
Au3?
198
Au
0
2.3 9 10
irradiated for 30 min at a thermal neutron flux of 2.53 9 1013 n cm-2 s-1 produced 2.3 9 107 Bq 198Au0. In addition, the decay trends in the samples activity were analyzed for a period of 1 month by LSC and HPGe. The activity of the samples was closely similar during 1 month and no significant different was observed. For this reason, it can be concluded that the reduction process had no considerable effect on the activity of the 198Au sample.
Conclusions At thermal neutrons energy range, there is a good agreement between the reported experimental data and the theoretical estimations using nuclear model calculations for production of 198Au (bmax = 0.96 MeV (98.6 %),
Production of cationic
198
Au3? and nonionic
198
Au0 for radionuclide therapy applications
cmax = 0.412 MeV (95.5 %) and T1/2 = 2.7 days) via nat Au(n,c)198Au reaction. The present study shows more than 2.5 9 107 Bq of 198Au activity could be produced by thermal neutron bombardment at a flux of 2.53 9 1013 n cm-2 s-1 for a period of 30 min. Activity of cationic 198 Au3? and nonionic 198Au0 were analyzed by LSC and HPGe. Consequently, Au3? reduction process before irradiation had no considerable effect on the activity of gold.
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