J Radioanal Nucl Chem DOI 10.1007/s10967-012-2345-2
Nuclear and chemical data for life sciences Moumita Maiti
Received: 16 November 2012 Ó Akade´miai Kiado´, Budapest, Hungary 2013
Abstract Use of reactor produced radionuclides is popular in life sciences. However, cyclotron production of proton rich radionuclides are being more focused in recent times. These radionuclides have already gained attention in various fields, including life sciences, provided they are obtained in pure form. This article is a representative brief of our contributions in generating nuclear data for the production of proton rich radionuclides of terbium, astatine, technetium, ruthenium, cadmium, niobium, zirconium, rhenium, etc., which may have application in clinical, biological, agriculture studies or in basic research. The chemical data required to separate the product isotopes from the corresponding target matrix have been presented along with a few propositions of radiopharmaceuticals. It also emphasizes on the development of simple empirical technique, based on the nuclear reaction model analysis, to generate reliable nuclear data for the estimation of yield and angular distribution of emitted neutrons and light charged particles from light as well as heavy ion induced reactions on thick stopping targets. These data bear utmost important in radiation dosimetry. Keywords Proton activation a-particle activation 7 Li-activation 9Be-activation 12C-activation Radiochemical separation Excitation function Thick target yield
M. Maiti (&) Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India e-mail:
[email protected] Present Address: M. Maiti Department of Physics, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India
Introduction: Importance of nuclear and chemical data A careful blending of basic science and advanced technology added a new dimension in today’s nuclear science. Exercise of nuclear techniques has been increased in leaps and bounds in almost all fields of science and technology. Use of radioisotopes or radiations has also been remarkably popular in life sciences in last few decades. Among diverse applications, nuclear medicine is an important emerging branch of medical science where radioactive isotopes are used in the welfare of mankind. Other areas include radiation dosimetry, environmental research, biology, agriculture, trace analysis, etc., which directly or indirectly work for the betterment of life. Historically, use of radioisotopes was first started in diagnostic nuclear medicine. In general, short-lived low energy c-emitters and b?/b--emitters, which impact low radiation dose to the patient, are preferred. 99mTc, due to its suitable half-life (6.01 h) and 140.511 keV c-rays, is the most extensively used radionuclide in scanning and imaging of almost all the body organs. So far, reactor facility has been the sole supplier of 99mTc obtained by milking its reactor produced parent 99Mo (66.0 h). In fact, more than ten million patients are treated each year by 99mTc around the globe. Unfortunately, due to the shutdown of huge number of reactors, supply of 99mTc is highly affected. Medical scientists worldwide are highly concerned regarding the matter. For instance, the Canadian Organization of Medical Physicists (COMP) met in 56th annual scientific meeting (2010) in the capital, Ottawa to discuss the latest issues of nuclear medicine where a dedicated session of the symposium addressed on ‘‘Medical Isotopes and Imaging: Where do we go from here?’’ This certainly implies to think about safe alternatives for our future survival. Accelerator production of proton rich radionuclides is
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highly relevant in the present scenario, especially remembering the recent Fukushima incident in Japan in March 2011. Therapeutic nuclear medicine is also developing very fast. Unlike diagnosis, high level of radioactivity is handled in therapeutic applications. The radionuclides emitting corpuscular radiations: a, b-, conversion or Auger electrons are generally used in therapy. Due to the short-range and high-linear-energy transfer in tissues, use of a-emitting radionuclides appears more promising than the b emitters in targeted therapy, where localization of dose is important. Desired radionuclide is attached to an appropriate chemical compound that transports it to a specific site for diagnosis or therapy. However, choice of radioisotope is crucial for a specific application. Production of radioisotope is strongly ruled by the mathematical and physical laws. Nuclear physics and chemistry took lead role in developing the field. Knowledge of nuclear data is of prime consideration for the choice of radionuclides for clinical or biological applications. Nuclear reaction data helps to optimise the production parameters, such as, suitable target-projectile combination, projectile energy, target thickness, and radionuclidic purity of the product. Decay data quantify the radiation effects in vivo or in vitro. Therefore, a continuously growing demand of nuclear data has been realized. On the other hand, chemical data deserve equal importance as they are mandatory for separation of trace amount of product from the bulk matrix [1]. In fact, nuclear chemistry has a vital role in harmony with nuclear physics to ensure the purity and quality of the product. Clinical radionuclides are preferably produced in high current low-to-medium energy accelerators by light ion (p, a, 3He, d) induced reactions as they offer better cross sections. However, the preference is not very strict and it is some time case specific. In general, production of a specific radionuclide in a heavy ion induced reaction cannot compete with that produced in a light ion reaction in view of yield. The advantage of heavy ion induced production is that it gives accessibility to produce a variety of proton rich radionuclides, which are hardly accessible in p- or a-induced reactions, located far from the stability line. Nevertheless, light-heavy ion induced reactions are efficient to produce reasonable amounts of desired radionuclide, sufficient for the biological studies in the laboratory scale. Therefore, exploration of all possible production routes becomes important in producing a particular isotope. Moreover, contrary to the light ion reactions, heavy ion reactions are less understood. Nuclear and chemical data are scare as well. This necessitates detail study on the heavy ion reactions to improve the knowledge of basic science. It is also important to remember that several high energy and high current accelerators, which have capacity
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to accelerate most of the isotopes in the Periodic Table, are upcoming. Therefore, it may be possible to combine improved knowledge of basic science and technology to work for life in near future. Generation and evaluation of nuclear data for radiation dosimetry is another important issue in this context as it observes growing interest to use high current particle (p, a, d) accelerators for medical and industrial use. The radiation environment of such accelerators is dominated by neutrons. For radiological safety, designing of adequate shielding becomes an issue to protect personnel from intense flux of secondary particles and gamma radiation created during the acceleration process and dumping. It is therefore necessary to estimate the energy and angular distribution of neutrons emitted from the interaction of protons or a-particles on various thick targets, where incident projectiles are completely stopped. This article presents our contribution in the generation of nuclear and chemical data relevant towards the production of radionuclides important in clinical/biological applications as well as in dosimetric studies. Nuclear characteristics of the radioisotopes [2] discussed here are presented in Table 1 along with their production routes and chemical separation procedure.
Production and separation of no-carrier-added radionuclides Quite a number of nuclear and chemical data have been generated for the production of no-carrier-added (nca) radionuclides suitable for biological or clinical applications if bind to an appropriate ligand. We exploited both, light ion (p, a) and heavy ion (7Li, 9Be, 12C, 16O) induced reactions on suitable natural targets to produce a-, b?- and c-emitting radionuclides using the national accelerator facilities: BARC-TIFR pelletron, Mumbai, and VECC-cyclotron, Kolktata, India. To develop efficient chemical methodologies for the separation of nca products from the bulk target we have mostly relied on liquid–liquid extraction (LLX) using two liquid ion exchangers, trioctylamine (TOA) and di-(2-ethylhexyl)phosphoric acid (HDEHP), as these exchangers have superior properties relating to immiscibility with aqueous phases, ion exchange capacity, selectivity, etc., compared to other exchangers [3]. We have also reported complexation stabilities of a few b?-emitting radionuclides with a peptide hormone, human chorionic gonadotropin (hCG). Our report relied on the c-spectrometric determination, however, in some cases it was combined to the inductively coupled plasma-optical emission spectrometry (ICP-OES) analysis. A brief of all the radionuclides studied so far are appended below.
Tl(9Be, xn)
7
Zr (7Li, xn)
nat
Zr (7Li, xn)
nat
Y(9Be, 3n)
Zr (7Li, xn)
nat
Y(9Be, 4n)
Zr ( Li, xn)
nat
Y(9Be, 4n)
Zr (7Li, xn)
nat
Y(9Be, 5n)
Tl(9Be, xn)
Pb(7Li, xn)
nat
nat
89
6
Bi(a, 2n)
Pb( Li, xn)
nat
209
Tl(9Be, xn)
Pb(7Li, xn)
nat
nat
89
6
Bi(a, 3n)
Pb( Li, xn)
nat
209
nat
Pb(7Li, xn)
nat
89
6
Bi(a, 4n)
Pb( Li, xn)
nat
209
Tl(9Be, xn)
Pb(7Li, xn)
nat
nat
89
6
Bi(a, 4n)
Pb( Li, xn)
nat
209
Pr( C, 4n) 149 Tb(EC/b?)
12
Pr(12C, p3n)
141
141
Pr(12C, 2n)
141
Pr(12C, 3n)
141
Pr(12C, 4n)
141
Tc/4.28 d
96
Tc/20.0 h
95
Tc/52.0 min
94m
Tc/4.883 h
94
Tc/2.75 h
93
At/7.214 h
211
At/8.1 h
210
At/5.41 h
209
At/1.63 h
208
Gd/9.28 d
149
Tb/17.609 h
151
Tb/3.48 h
150
Tb/4.16 min
149m
Tb/4.118 h
149
141
Pr(12C, 4n)
Isotope/T1/2
Reaction
7?
9/2?
2?
7?
9/2?
9/2-
5?
9/2?
6?
7/2-
1/2?
2-
11/2-
1/2?
Spin
e (100)
e (100)
e (100) IT(\ 0.1)
e (100)
e (100)
a (41.8)
e (58.2)
a (0.175)
e (99.825)
a (4.1)
e (95.9)
a (0.55)
e (99.45)
a (0.00043)
e (100)
a (0.0095)
c: 778.22(99.76), 812.54(82) 849.86 (98)
c: 765.789(93.8), 1073.713(3.74)
b?: 1094.2 (67.6)
c: 871.05(94.2), 993.19(2.21)
b?: 358.3 (10.5)
c: 702.67(99.6), 849.74(95.7) 871.05 (99.9)
b?: 360.7 (8.63), 292.4 (1.59)
c: 1362.94(66.2), 1520.28(24.4)
a: 5869.5 (41.8)
c: 245.35 (79), 1181.4 (99), 1483.35 (46.5)
a: 5647(4.1)
c: 545.0 (91.0), 781.9 (83.5) 790.2(63.5)
c: 660.1(90), 685.2(97.89), 1028 (27)
c: 149.735(48), 298.634(28.6), 346.651(23.9)
c: 287.357(28.3), 251.863(26.3)
b?: 1360(14.2)
e (99.99)
a (\0.05)
a: 3999(0.022) b?: 804(21) c: 638.050(72), 496.242(14.6)
e (100)
c: 796.0(97), 165.0(7.3)
a (0.02)
a: 3967(16.7) b?: 638.0(3.8)
e (99.98)
c: 164.98 (26.4), 352.24 (29.4)
a (16.7)
Particle energy in keV (Intensity %)
e (83.3)
Decay mode (%)
Table 1 Production, chemical separation and nuclear characteristics [2] of the radionuclides presented in this article
Nca Tc-bulk Zr and nca Nb; LLX: HCl and TOA/cyclohexane
HCl and Dowex-1
Nca Tc-bulk Y; LLX: HCl and TOA/cyclohexane; SLX: HCl and Dowex-50
Nca At-bulk Tl; LLX: liquor ammonia and HDEHP/cyclohexane
Nca Gd - bulk Pr; LLX: HCl and HDEHP/cyclohexane (in presence of H2O2)
Nca Tb - bulk Pr and nca Gd; LLX: HCl and HDEHP/ cyclohexane (in presence of hydrazine sulphate)
Chemical separation
[14–16]
[10–13]
[9]
[4, 5]
Ref.
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123
123
Y(12C, 4n)97Rh(EC) 89 Y(12C, p3n)
89
Y(p, n)
Y(p, 2n)
Hf(6Li, xn) Hf(7Li, xn)
Lu(9Be, xn)
6
Hf(7Li, xn)
Hf(7Li, xn)
W(p, xn)
nat
nat
Ta (a, xn)
nat
W(p, xn)
nat
Hf(7Li, xn)
Hf(6Li, xn)
nat
nat
Ta(a, xn)
nat
W(p, xn)
nat
nat
Hf( Li, xn)
nat
Ta (a, xn)
nat
W(p, xn)
nat
nat
nat
nat
Ta (a, xn)
nat
W(p, xn)
nat
Hg(p, xn)
nat
Hg(p, xn)
nat
Hg(p, xn)
nat
Ag(p, xn)
nat
Ag(p, xn)
nat
89
89
Zr(p, xn)
nat
97
Nb (7Li, 3n)
93
Re/3.7186 d
186
Re/35.4 d
184
Re/70.0d
183
Re/64.0 h
182
Re/19.9 h
Tl/7.42 h
181
199
Tl/26.1 h
Tl/3.042 d
200
201
Cd/461.4 d
109
Cd/6.5 h
107
Zr/3.268 d
Zr/83.4 d
89
88
Nb/14.6 h
90
Ru/2.83 d
Isotope/T1/2
Reaction
Table 1 continued
1-
3-
5/2?
7?
5/2?
1/2?
2-
1/2?
5/2?
5/2?
9/2?
0?
8?
5/2?
Spin
ABS: Na-salt and 50 % PEG-4000
c: 137.157(9.47) b-: 359.2(70.99), 306.1(21.54)
b-(92.53)
c: 111.2174(17.2), 792.067(37.7), 903.282(38.1)
c: 162.3266(23.3), 208.8107(2.95), 291.7282(3.05)
b?: 762(1.4)
c: 100.12(14.4), 1121.4(32), 1221.5(25)
c: 365.5(56), 360.7(20)
c: 208.20(12.3), 455.46(12.4), 247.26(9.3)
c: 1205.75(30), 579.300(13.7), 828.27(10.8)
c: 167.43(10.0), 135.34(2.565)
c: 88.0336(3.7)
HNO3 and TOA/cyclohexane
Micro quantity Re-bulk Hf; LLX: HNO3 and HDEHP/cyclohexane
Micro quantity Re-bulk W; LLX: HNO3 and TOA/cyclohexane
Nca Tl-bulk Hg; LLX: HNO3 and TOA/cyclohexane
Nca Cd-bulk Ag; Precipitation of AgCl
b?: 395.5(22.74) c: 93.124(4.7), 828.934(0.163)
SLX: H2SO4 and Dowex-50
Nca Zr-bulk Y; LLX: H2SO4 and HDEHP/cyclohexane
Nca Nb-bulk Zr; LLX: HCl and TOA/cyclohexane
ABS: Na-salt and 50 % PEG-4000
Column: Dowex-50/HCl
SLX: HCl and Dowex-50
Nca Ru-bulk Y; LLX: HCl and HDEHP/cyclohexane
SLX: HCl and Dowex-50
Nca Ru-bulk Nb; LLX: HCl and HDEHP/cyclohexane
Chemical separation
c: 909.15(99.04)
c: 392.9(97.3)
b?: 662.2(51.1)
c: 141.178(66.8), 1129.224(92.7)
c: 215.70(85.62), 324.49(10.79)
Particle energy in keV (Intensity %)
e (7.47)
e (100)
e (100)
e (100)
e (100)
e (100)
e (100)
e (100)
e (100)
e (100)
e (100)
e (100)
e (100)
e (100)
Decay mode (%)
[29]
[28]
[27]
[24]
[23]
[22]
[21]
[20]
Ref.
J Radioanal Nucl Chem
J Radioanal Nucl Chem
Terbium 149
Tb (T1/2 = 4.118 h, decay mode: EC 83.3 % and a 16.7 %, a-energy 3.97 MeV) is among the few a-emitting radionuclides, which occupied centre stage of discussion recently, for targeted therapy. It forms stable labelling with chelating ligands, macromolecules or peptides. However it has always been a problem to produce this particular radionuclide, located far away from the line of stability. Production of 149Tb is difficult in light ion induced reactions as the required *50 MeV proton or *100 MeV a-particles are commonly not available in accelerators. 1–2 GeV proton induced spallation reaction can produce 149Tb, but the available facility is limited. Moreover, it is hard to separate nca Tb from the adjacent bulk target or coproduced radionuclides due to the similar chemical properties of lanthanides. This situation forced to think about the heavy ion induced production of 149Tb. We investigated in detail 12C induced reaction on natPr target [4, 5]. Two earlier measurements from a- and online c-spectrometry showed two orders of magnitude difference in cross-section values of 149 Tb [6, 7]. Therefore, a third measurement was necessary to justify earlier reports and the ambiguity, if any, lies between them. Production cross sections of evaporation residues, 149Tb, 150Tb, 151Tb, and 149Gd, have been measured using the stacked-foil technique followed by off-line cspectrometry in 12C-induced reactions on naturally abundant mononuclidic praseodymium target in the 44- to 79-MeV incident energy range. Measured data are interpreted by comparison with those measured by a-spectrometry, online-c-spectrometry and theoretical predictions of PACE4. Only about 5 and 14 % of the theoretical cross sections have been measured for 149Tb and 150Tb, respectively. The newly measured cross sections of 149Tb complement those measured earlier by a-spectrometry. This observation indicates that the interaction of a 12C projectile with a 141Pr target forms mostly excited compound-nucleus 153 Tb in the high-spin state, which preferentially decays to the short-lived high-spin state 149mTb (4.16 min; 11/2-). 149m Tb decays directly to 149Gd via 149mTb(EC/b?)149Gd reaction. The 149Tb (1/2?) is produced only from low-spin compound nuclei of 153Tb and this gives low cross-section values for 149Tb. Nevertheless, it is noteworthy that two independent measurements of excitation function of 149Tb using a- and c- spectrometry complement each other, with a confirmation of a low cross-section value of 149Tb. Cross sections of 151Tb were found comparable to the theory as expected. The high cumulative cross sections of 149Gd also shed light on the nuclear reaction mechanism as it is mostly the product of 149mTb(EC/b?)149Gd reaction. The feasibility of production of 149Tb in p- and a-induced reactions on gadolinium isotopes has been studied theoretically using model code TALYS [8].
Radiochemical separation of nca Tb was aimed from the bulk praseodymium target [5]. A natural praseodymium (141Pr) foil of (99.9 % purity) of 15 mg/cm2 thickness was bombarded by 71.5 MeV 12C6? ions for 9.3 h up to a total charge of 1,428 lC. Nca 149,150,151Tb radionuclides were produced in the target matrix along with 149Gd, which is mostly the decay product of 149Tb. Compound-nucleus reaction plays the key role at the selected projectile energy. The production of 149Tb was not satisfactory, though it had the highest production among others. On the other hand, production of nca 149Gd was found to be comparatively high at the end of bombardment (EOB). Nca 149–151Tb was separated from bulk Pr and coproduced nca Gd by LLX using aqueous HCl and liquid cation exchanger HDEHP dissolved in cyclohexane. Quantitative separation of nca Tb was obtained from bulk Pr by 0.5 % HDEHP from 0.1 M HCl in presence of a pinch of hydrazine sulphate which helped to reduce Pr(IV) to Pr(III) state and reduced the extraction of nca Gd. A high separation factor (DTb/DPr) of 4.7 9 105 was achieved at this experimental condition. In the later stage, nca Tb was separated from nca Gd using the same extraction condition, which yields a high separation factor (DTb/DGd) of 5.2 9 104. Nca Tb may be back extracted by both, 6 M HCl and 0.1 M diethylenetriaminepentaacetic acid (DTPA) in 1 M NaOH from the HDEHP phase. Gadolinium The applications of lanthanide radionuclides are limited compared to that of other elements in the Periodic Table. The fact may be due to the unavailability of suitable radionuclides of lanthanides in the nca form. 153Gd has found applications in the diagnostic nuclear medicine. However, 153Gd has long half-life of 240.4 d, which is certainly a disadvantage for clinical applications. In this circumstance, comparatively short-lived 149Gd (9.28 d), having intense c-rays, may act as a potential alternative of 153Gd. Production of nca 149 Gd and its purification from the target matrix is therefore important. We aimed to produce high purity nca 149Gd from natural praseodymium target by 12C activation [9]. The natPr target was irradiated by 71.5 MeV 12C6? ions for 560 min up to a total charge of 1,428 lC. Nca 149Tb and 149 Gd radionuclides were produced in the target matrix. 149 Gd was produced via direct: 141Pr(12C,p3n)149Gd and indirect: 141Pr(12C,4n)149mTb(EC)149Gd and 141Pr(12C,4n) 149 Tb(EC)149Gd reactions. The batch yield for 149Tb, 150Tb, 151 Tb and 149Gd were found to be 86, 37, 7 and 70 kBq lA-1 h-1 at EOB, respectively. After the complete decay of short-lived 149Tb (4.118 h), nca 149Gd was separated from the bulk Pr target using LLX. The maximum separation was achieved at 1 % HDEHP and 0.1 M HCl in presence of H2O2, where about 80 % nca 149Gd was extracted to the organic phase leaving the bulk Pr quantitatively in the
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aqueous phase, resulting to a high separation factor (DGd/DPr) of 2.45 9 103. Addition of H2O2 increased the separation factor probably due to the fact that H2O2 helped Pr to obtain Pr?4, which eventually increased the difference of ionic radii between Pr?4 and Gd?3, and as a consequence the difference between the extraction behaviors of these two elements increased. The indirect production of nca 149Gd was appeared advantageous compared to earlier methods and it provides high radionuclidic purity. The developed method is simple, fast, reliable and takes only 80 min. Astatine Astatine has no naturally abundant isotopes, hence need to be produced artificially. All the known isotopes of astatine are short-lived, the longest one being 210At, with a half-life of 8.1 h. Astatine is the heaviest known halogen, therefore expected to show chemical properties similar to those of its lighter homologues. However, unlike other halogens, astatine is semi-metallic in nature. Therefore, astatine chemistry is severely influenced by the experimental environment [10]. Due to the practical difficulty of production, it is one of the least studied elements in the Periodic Table. Favourable halflife, decay mode and 5.867 MeV a-particles of 211At seemed to be ideal for the targeted therapy. Most commonly, 211At is produced in an accelerator via 209Bi(a,2n)211At reaction by 28 MeV a-particles. Multiple reports are available towards optimization of the production of 211At in 209Bi(a,2n)211At reaction. However, theoretical studies are rather few compared to experiment. Recently, we carried out a systematic theoretical investigation to understand various possible production routes of 209-211At from light ion (a,3He) and heavy ion (6Li, 7Li, 9Be) induced reactions on natural and enriched targets up to 100 MeV incident energy [11]. The study sheds light on the contribution of various nuclear reaction mechanisms such as direct, preequilibrium and equilibrium reactions to the total production cross-section. In the medium energy range, equilibrium and preequilibrium reactions are the dominating mechanisms. Direct reactions play no role in producing astatine radionuclides and may have some contribution only in case of high incident energies. Excitation functions of a number of target-projectile combinations were estimated using the nuclear reaction model codes, TALYS, ALICE91 and PACE-II and compared with the previously reported crosssection values, wherever available. The reaction channels include 209Bi(a,xn) [x = 2,3,4], 209Bi(3He,xn) [x = 1–3], 208 Pb(6/7Li,xn) [x = 3–6], 203/205Tl(9Be,xn) [x = 1–5]. It has been shown that though light ion induced reactions have higher cross sections, the 7Li and 9Be induced reactions on natPb or natTl have comparable possibility for the production of 209,210,211At. However, production of 211At
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will increase significantly reducing the production of impurity radionuclides, if the enriched 208Pb target is used. In order to validate the theory, we experimented on the two heavy ion induced reactions: 9Be ? natTl and 7 Li ? natPb. It is noteworthy to mention that 9Be projectile was used for the first time to produce any astatine radionuclides. Formation cross sections of the evaporation residues, 207,208,209,210At, produced in (7Li/9Be, xn) channel, have been measured by the stacked-foil technique followed by the off-line c-spectrometry at the low incident energies (\50 MeV). Measured excitation functions have been explained in terms of compound nuclear reaction mechanism using Weisskopf-Ewing and Hauser-Feshbach model. The measured cross-section values were lower than the respective theoretical predictions. Due to the limitation in available accelerator facility, the report covers a small incident energy range. Though theoretical investigation shows considerable possibility of producing 211At (*400 mb) in 7Li induced reaction on natPb [12], it was not possible to identify 211At by c-spectrometry in the present experiment due to its low intensity c-emissions. To develop chemical separation technique, we used 46.2 MeV 9Be beam of 630 nA current for 200 min to produce nca 208,209,210At on a 4.0 mg/cm2 Tl2CO3 target. After irradiation, nca At radionuclides were separated by the LLX technique using HDEHP dissolved in cyclohexane and liquor ammonia solution. Astatine remained quantitatively in the aqueous phase, showing its chemical form as At-1. Tl? was extracted in the HDEHP phase. However, a slight contamination of bulk in the aqueous phase could not be avoided [13]. It is necessary to mention that the batch yields of astatine isotopes in both 7Li and 9Be induced reactions are low compared to a-induced reaction. Therefore, these two methods could be utilized in production of radioastatine for tracer use rather than the medical application [13]. Technetium The magical radionuclide, 99mTc (6.006 h) has long been used most effectively in diagnostic study. However, despite favorable moderate half-lives suitable for diverse applications, isotopes of technetium, 93,94,94m,95,95m,96Tc, are seldom discussed. Usually proton rich Tc isotopes are produced in medium energy accelerators using p-, d-, 3He-,a-particle induced reactions on Mo or Nb target. Heavy ion induced productions of those isotopes have hardly been investigated. Recently, we carried out extensive work on the production of Tc isotopes by heavy ion activation, in particular, 7 Li ? natZr and 9Be ? natY as possible production routes of 93–96 Tc [14–16]. In order to choose the projectile energy range theoretical excitation function of each target-projectile combination was investigated using the nuclear reaction model
J Radioanal Nucl Chem
codes, ALICE91 and PACE-II. The experimental excitation functions of the evaporation residues produced in 7Li ? natZr and 9Be ? natY reactions were measured over energy ranges 37–45 MeV and 30–48 MeV, respectively. The experimental excitation functions were well validated by PACE-II. However, some anomalies were observed in ALICE-91 predictions. The cross-section data essentially revealed that the compound nuclear reaction was the key mechanism in the energy range studied. The most interesting part of the work was that the excitation function for production of 94,95Tc by nat Y ? 9Be was comparable with the 93Nb ? a reaction [14]. The resulting yield in the natY ? 9Be reaction is, however, much smaller than the 93Nb ? a reaction, because the range of 9Be in the matter is shorter than that of the a-particle [10]. This study also showed that an affordable compromise in yield would be effective if mononuclidic target is chosen in heavy ion induced production [14]. It is again notable that we first used 9Be as projectile for the production of proton rich technetium isotopes. Besides cross-section measurement, we carried out some radiochemical experiments with Tc radionuclides produced by heavy ion activation on natZr and natY targets [15, 16]. An yttrium target of 4.9 mg/cm2 thickness was bombarded with 37 MeV 9Be beam. The nca 93,94,95Tc was separated from the bulk yttrium both by LLX and solid–liquid extraction (SLX) techniques [16]. TOA dissolved in cyclohexane was used in LLX as liquid anion exchanger. Similarly, DOWEX-50 and DOWEX-1 were used as cation and anion exchangers, respectively, in the SLX system. It was observed that nca Tc radionuclides were extracted into the TOA phase from HCl media almost independent of HCl concentration and the bulk Y behaved just the reverse, i.e., it remained in the aqueous phase in the entire acidity range studied (10-5 – 1 M HCl). The logical conclusion from this behaviour is that Tc forms anionic complexes like [TcCl6]-, while Y has strong cationic chemistry. Thus a high separation factor (DTc/DY) *6 9 103 was obtained at the optimum condition, 10-4 M HCl and 0.5 M TOA. Similar separation factors were obtained in SLX when 10-3 M HCl was used as aqueous phase and DOWEX 50 or DOWEX 1 was used as the resin phase. Similarly, natural zirconium was irradiated with 7Li beam of 42.5 MeV energy [15]. Along with 93,94,94m,95,96Tc, 90,96 Nb were also produced in the matrix. The LLX with 0.01 M HCl and 0.1 M TOA/cyclohexane extracted nca 93,94,94m,95,96 Tc radionuclides in the organic phase, while 90,96 Nb and the bulk Zr quantitatively remained in the aqueous phase. The extracted Tc radionuclides were back extracted into the aqueous phase by 0.1 M DTPA in 0.1 M NaOH. In the developed processes, radiochemical yield of nca Tc was achieved *80 % and the radiochemical purity was 100 %. The extraction profile of Zr, Nb and Tc corroborated with earlier experimental data [17–19].
Ruthenium Proton rich 97Ru (2.83 d) decays to 97Tc via EC decay mode and emits only two intense c-lines 215.70 keV (85.62 %) and 324.49 keV (10.79 %) energy. Ruthenium has several oxidation states, which exhibit rich chemistry of Ru-complexes. The combination of excellent physical property of 97Ru and high chemical reactivity made it appealing for labelling compounds for delayed studies in diagnostic as well as therapeutic applications. The 97Ru has been produced so far either by neutron activation or by light charged particle activation. The reactor produced 97Ru through 96Ru(n,c)97Ru reaction has limited applications for in vivo studies due to low specific activity. In view of the growing importance, we have investigated two new production routes of 97Ru: natNb ? 7Li and natY ? 12C reaction [20, 21]. Nuclear reaction model calculations illustrate reasonable possibility for the production of 97Ru in aforesaid combinations. Based on theory, we measured excitation functions of the evaporation residues in both cases in relevant projectile energy range. nat
Nb ? 7Li
Theory predicts that 7Li-induced reaction on natNb produce only 97Ru isotopes below 40 MeV projectile energy. Therefore, 7Li ? natNb reaction at appropriate projectile energy in conjunction with efficient chemistry might produce 97Ru of high radiochemical and radioisotopical purity. A natural Nb foil of 20 mg/cm2 thickness was irradiated with 32 MeV 7Li beams for 6 h up to a total charge of 985 lC which yields * 1 MBq lA-1 h-1 activity of 97Ru at EOB. Nca 97Ru was separated from the bulk Nb by LLX using HDEHP dissolved in cyclohexane and SLX using cation exchanger DOWEX-50 in combination with aqueous HCl. The LLX technique was found to be superior over the SLX technique with respect to radiochemical yield and purity of 97Ru radionuclides [20]. nat
Y?
12
C
97
Ru was produced by bombardment of 70 MeV 12C projectiles (with an average beam current of 90 nA) for 3 h on a nat Y target. Two reaction channels, (i) natY(12C, 4n)97Rh(EC) 97 Ru (ii) natY(12C, p3n)97Ru, contributed in the production of 97 Ru. Nca Ru has been separated quantitatively from the bulk yttrium by LLX and SLX using liquid and solid cation exchangers. We have also separated nca Ru by column chromatography and aqueous biphasic systems (ABS), where high concentration of sodium salts were used in combination with 50 % PEG (Polyethylene glycol)-4000 in order to form various ABS systems, following the green chemistry approach as they do not use any organic solvents.
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Thus we carefully combined radiochemistry to green chemistry. Simplicity is the novelty in all the developed separation techniques [21]. Niobium 90
Nb (14.6 h) emits positrons (average b? energy of 662 keV) and Auger electrons with favorable energy and intensity (2.02 keV, 77.7 % and 13.4 keV, 17.5 %). Therefore it is also a potential candidate radionuclide for targeted therapy. A few reports described production of nca Nb from a-activated Y or Mo targets and its separation from the target matrix. However, no where 90Nb was free from radionuclidic impurity, which is an important issue in clinical applications. Hence, we aimed to produce pure 90Nb, free from coproduced radionuclides, from natural zirconium target and developed a fast and efficient radiochemical separation method. 90Nb (14.6 h) was produced by irradiating a natural zirconium foil of 4.9 mg/cm2 thickness by 13 MeV proton beam. Nca 90Nb of *27 kBq activity was produced in the target matrix. LLX technique was applied using TOA diluted in cyclohexane to separate nca 90Nb from bulk zirconium matrix. About 70 % radiochemical yield of nca 90Nb was achieved with a separation factor of 1.4 9 104 [22]. Zirconium 89
Zr (3.268 d), generally produced by p- or d-induced reaction on natural yttrium target, is a demanding clinical radionuclide, especially for positron emission tomography (PET). 89Zr labelled with monoclonal antibodies were proposed for bio-distribution studies. 89Zr isotope is also used in the study of biokinetics of zirconium in human. Several chemical separation techniques have been reported so far to separate nca 88,89Zr from natural yttrium target. We followed conventional method to produce nca 88,89Zr from natY target, but compared two chemical separation methods; LLX by HDEHP in cyclohexane and SLX using Dowex 50 W-X8 in combination with H2SO4 along with the species analysis. Both LLX and SLX offer simple, single step separation scheme and high separation factor. However, the SLX provides better yield and much higher separation factor (1.1 9 107) compared to LLX (4.7 9 103). Therefore to obtain high radiochemical purity, SLX may be a preferred method which does not involve any environmentally hazardous chemicals [23]. Another greener approach was developed to separation nca Zr from natural Y using sodium-salt and 50 % PEG-4000 in ABS.
environmental study of Cd pollutant. Nca 109Cd (462.6 d) is suitable to be used in long term metabolic studies of cadmium at subcellular and molecular level whereas nca 107Cd (6.5 h) is useful in short-term biological studies. Both, 107Cd and 109Cd, are useful in the nuclear medicine when used as 109 Cd/109mAg and 107Cd/107mAg generator system. Development of efficient separation technique is therefore important to address the purity of the tracers. We produced nca 107,109Cd radionuclides by bombarding natural silver target matrix with 13 MeV protons, which gave *15 MBq lA-1 h-1 yield for nca 107Cd at EOB. The nca cadmium radionuclides were separated from the natural silver target matrix by simply precipitating Ag as AgCl. The developed method is an example wherein green chemistry is used in trans-disciplinary research. The method is also simple, fast, cost effective and environmentally benign. This report shows that the classical chemistry is still relevant to push forward the modern days research [24]. Thallium Thallium isotopes have significant application in diagnostic nuclear medicine. 201Tl, a potassium analogue, is one of the important radionuclides in myocardial imaging. Use of 201 Tl (72.91 h) and 199Tl (7.42 h) includes the scanning of malignant bone tumours, soft tissue tumours, brain tumours, lung cancer, prostate cancer, breast cancer etc. Earlier heavy ion activation methods for production of 199Tl were proposed from our laboratory [25, 26]. For the first time, we used natHg2Cl2 target to produce nca 199,200Tl radionuclides in natHg(p, xn) reaction using 21 MeV proton beam for 9 h with *140 nA beam current. A number of short-lived Tl isotopes, 197Tl (2.84 h), 198Tl (5.3 h) and 198mTl (1.87 h), were produced along with 199,200Tl. However, short-lived isotopes were almost decayed after 14 h of EOB. Only 199,200 Tl were found abundant for radiochemical analysis. LLX technique was employed in order to separate radiothallium from the bulk mercury matrix using TOA dissolved in cyclohexane. In order to ensure the absence of stable Hg in Tl fraction, the entire process was repeated with stable salts of Hg and Tl and the extent of separation was examined by ICP-OES. High separation factors were observed in both radiometric and ICP-OES technique when 0.1 M HNO3 and 0.1 M TOA were used as aqueous and organic phase respectively. The Hg contamination was found less than 0.3 ppm in the aqueous phase containing Tl after three times extraction at the optimal condition [27]. Rhenium
Cadmium There is a definite demand of nca cadmium tracers, namely, 107,109 Cd. 109Cd is popular as a radioactive tracer for
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Among rhenium isotopes, 186Re and 188Re are established as therapeutic radionuclides. Short-lived 99mTc has some limitations to be used in long term study, though it plays a
J Radioanal Nucl Chem
key role in diagnostic nuclear medicine. Rhenium is the higher homologue of technetium and possesses rich coordination chemistry. Hence, proton rich rhenium radionuclides of suitable half life may serve as alternative of 99mTc in desired cases. In order to produce them in an accelerator, we explored theoretically various reaction channels leading to the production of proton rich rhenium radionuclides, 181,182,183,184,186 Re, for suitable biological applications. The possible production routes include both, light- and heavy ion induced reactions: natW (p, xn)181–184,186Re, nat Ta (a, xn)181–184Re, natHf (6Li, xn)181–183Re, natHf 7 ( Li, xn)181–184Re, and natLu (9Be, xn)181–179Re. Excitation functions were calculated using nuclear reaction model codes and compared with the measured data wherever available. For the first time, this study discussed about the possibility of light-heavy ion (6,7Li and 9Be) induced production of proton rich rhenium radionuclides [28]. The product nca Re need to be separated from the bulk assay. We therefore developed an experimental simulation of the separation of trace quantity of Re from the two bulk matrices of W and Hf by LLX using TOA and HDEHP dissolved in cyclohexane and aqueous HNO3. The presence or absence of Re and W or Hf were monitored by ICP-OES. A good separation was achieved in both cases [29].
hCG complexes with b-emitting radionuclides hCG is a peptide hormone, whose one of the structural subunits is identical to that of thyroid-stimulating hormone (TSH). As a consequence, the receptors of TSH also act as receptor for hCG hormone. This interesting property of hCG prompted us to study its complex formation ability with various nca b-emitting isotopes, 61Cu (3.3 h), 62Zn (9.2 h), 90Nb (14.60 h), 99Mo (66.02 h), with hCG molecule. Stability of the hCG-M (M = metal ions; 99Mo, 61Cu, 62 Zn and 90Nb) complexes was investigated by dialysis with respect to triple distilled water and ringer lactate solution, which has the same composition as extracellular fluid, following the modified Free-Ion Selective Radiotracer Extraction (FISRE) technique [30, 31]. If first order reaction is assumed between hCG (L) and radionuclides (M), dissociation rate of the hCG-M complex (ML) can be written as:
dfðMLÞmþn g ¼ kd fðMLÞmþn g ka fM m gfLn g dt
where, kd and ka are dissociation and association constants, respectively. The dissociated radionuclides were continuously removed from the dialysis sack leaving hardly a chance of re-association of L and M, hence, above equation is simplified to:
dfðMLÞmþn g ¼ kd fðMLÞmþn g dt whose solution is kd t fðMLÞmþn g ¼ fðMLÞmþn t t0 ge
The dissociation constant (kd) is the slope of the plot ln{hCG-M} vs. time. The M(99Mo,61Cu,62Zn)-hCG complexes have lesser half lives (1–1.5 h), while 90NbhCG complex offers a higher stability in extracellular fluid (T1/2 = 5.2 h). The complexes reported by us might come out as a useful alternative in the treatment of toxic multinodular goitres, whose only satisfactory treatment so long has been surgery. However, exact fate can be observed only after rigorous in vivo experiments [32].
Nuclear data for radiation dosimetry High current proton accelerators are increasingly used in producing PET and SPECT isotopes required for diagnosis and therapy. It is therefore necessary to assess radiation environment around these accelerators during operation and shutdown for the safe use of these facilities. Studies on neutron estimation are still not in the proper focus, though neutron plays a role of villain dominating the radiation environment in an accelerator. To contribute in this direction, we have studied energyangle distributions of emitted neutrons and light charged particles from both light and heavy ion induced reactions in thick stopping targets in the low to intermediate energy range mainly in the framework of preequilibrium and equilibrium reaction mechanisms using different nuclear reaction model codes, namely, ALICE91, PRECO-2000, EMPIRE-II, BME, PACE and HION, with proper modifications for thick stopping target [33–38]. The major emphasis of the work has been on the development of simple empirical formalisms for estimation of total yield, energy and angular distribution of neutrons from p- and a-particle- induced reactions on wide range of targets, Be to Bi, based on the parameterization of computed results in the incident energy range from 25 to 200 MeV. The developed formalisms requires only two input parameters; target mass, projectile (p or a) energy, hence computation time is greatly reduced (a factor of 500). It also reproduces reliably the available experimental neutron emission data [33, 34]. In case of a-particle induced reactions, we showed that the neutron distribution from the two initial configurations of a-particles i.e. 4particle-0hole and 5particle-1hole differ in angular distributions with a former being more forward peaked. The relative contribution of the 4particle-0hole configurations was found to vary as the cosine of the angle of emission [35].
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Simple empirical expressions are also developed for the estimation of total flux and dose of emitted neutrons and their transmission through the concrete shield from proton induced reactions on different target materials in the 25–200 MeV energy range. The estimated attenuation length of neutrons in the concrete shield shows increasing trend with incoming energy and slab thickness. These empirical formalisms will be useful if incorporated in large scale particle transport simulations [36, 37]. Apart from p or a-induced reactions, empirical formalism has also been developed for estimation of angular distribution of neutrons emitted from heavy ion induced reactions for energies up to about 10A MeV. This has been accomplished through systematic analysis of the available experimental data from our work and others’ works. An exponential function of emission angle of neutron has been found to reproduce the distribution involving the parameters like, projectile energy, target and projectile masses. A good agreement was obtained when computed neutron distribution was compared to the experimental data [39]. To validate the theoretical propositions, we experimented to measure angular yield and dose distribution of neutrons from proton and heavy ion induced reactions in thick targets. Pulse shape discrimination technique was adopted to distinguish neutrons from gammas in liquid scintillator detectors. Both, unfolding of the neutron pulse shape spectra and timeof-flight techniques, are used to determine the energy-angle distributions of emitted neutrons. Measured data; for instance, 19 F(110 MeV) ? Al, 19F(100 MeV) ? Cu, p(20 MeV) ? Be, p(20 MeV) ? Cu, etc., were analyzed in terms of different nuclear reaction model codes and previously reported formulations [40–44].
Future scope in the field Uninterrupted progress of science and technology keeps ourselves dynamic to be more precise towards the quality life. The field of diagnostic/therapeutic nuclear medicine is developing. In order to avoid reactor facilities, demand of accelerator produced radionuclides has been realized. As a first step, a large number of proton rich radionuclides have been proposed for both, diagnostic and therapeutic applications through some ingenious interplay of biology, medicine and technology. However, use of the proposed radionuclides is till date limited in medical science except the enormous application of 99mTc and a limited application of few radionuclides like 67Ga, 131I, 177Lu, etc. In order to apply those radionuclides successfully, we need more research to get specific information on the production parameters to reduce the impurity of coproduced radionuclides. Improved separation chemistry, speciation study and designing of suitable
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carrier are also vital to maintain radiochemical purity of the product for in vivo or in vitro study. Technology of accelerator is planning to cover large energy region. Several high current and high energy accelerators are coming up. Studies on nuclear reactions in those accelerators and development of chemical separation technique will be interesting to produce radionuclides of varied importance. High energy accelerators may be exploited in life sciences. For instance, in the production of satisfactory amount of multi-tracer that will have exciting application in environmental or biological investigations. Generation of nuclear data is also essential in view of radiological safety. Acknowledgments I sincerely acknowledge my collaborators for their contributions and advice in original work. My sincere thanks go to the Council of Scientific and Industrial Research (CSIR) for providing necessary grants. This work is as part of the Saha Institute of Nuclear Physics-Department of Atomic Energy, XI five year plan project ‘‘Trace Analysis: Detection, Dynamics and Speciation (TADDS)’’ and XII five year plan project ‘‘Trace Ultratrace Analysis and Isotope Production (TULIP)’’.
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