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At least 19 records

Optimized anion exchange column isolation of zirconium-89 (89Zr) from yttrium cyclotron target: Method development and implementation on an automated fluidic platform

Zirconium-89 (89Zr), produced by the (p,n) reaction from naturally monoisotopic yttrium (natY), is a promising positron emitting isotope for immunoPET imaging. Its long half-life of 78.4 h is sufficient for evaluating slow physiological processes. A prototype automated fluidic system, coupled to on-line and in-line detectors, has been constructed to facilitate development of new 89Zr purification methodologies. The highly reproducible reagent delivery platform and near-real time monitoring of column effluents allows for efficient method optimization. The separation of Zr from dissolved Y metal targets was evaluated using several anion exchange resins. Each resin was evaluated against its ability to quantitatively capture Zr from a load solution that is high in dissolved Y. The most appropriate anion exchange resin for this application was identified, and the separation method was optimized. The method is capable of a high Y decontamination factor (>105) and has been shown to separate Fe, an abundant contaminant in Y foils, from the 89Zr elution fraction. Finally, the performance of the method was evaluated using cyclotron bombarded Y foil targets. The separation method was shown to achieve >95% recovery of the 89Zr present in the foils. The 89Zr eluent, however, was in a chemical matrix not immediately conducive to labeling onto proteins. The main intent of this study was to develop a tandem column 89Zr purification process, wherein the anion exchange column method described here is the first separation in a dual-column purification process.

Zirconium-89, ImmunoPET, medical isotope, automati↗

Hyperfine interactions in titanates: Study of orbital ordering and local magnetic properties

Hyperfine magnetic fields induced on the nuclei of nonmagnetic ions {sup 139}La and {sup 89}Y in LaTiO{sub 3} and YTiO{sub 3}, respectively, have been microscopically calculated. The dependence of the hyperfine fields on the orbital and magnetic structures of the compounds under study has been analyzed. The comparative analysis of the calculated and known experimental data confirms the existence of the static orbital structure in lanthanum and yttrium titanates.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Nuclear Data Sheets for A = 89

The evaluated experimental data are presented for 14 known nuclides of mass 89 (Ge, As, Se, Br, Kr, Rb, Sr, Y, Zr, Nb, Mo, Tc, Ru, Rh). New data on high–spin excitations are available for {sup 89}Kr, {sup 89}Rb, {sup 89}Sr, {sup 89}Tc and {sup 89}Ru, including a superdeformed structure in {sup 89}Tc. Fluorescence studies in {sup 89}Y have revealed a large number of new levels in 7–11 MeV range. New two–neutron transfer data are available for {sup 89}Zr. New direct and precise measurement of atomic masses of {sup 89}Se, {sup 89}Br, 89{sup K}r, {sup 89}Rb, {sup 89}Mo and {sup 89}Tc have greatly improved the Q value landscape in this mass region. This work supersedes previous A=89 evaluation published in 1998Si31, and also the older ones 1989Si20, 1975Ko21, and M.W. Johns et al., Nuclear Data Tables A 8, 373 (1970). In spite of extensive experimental work on the isobaric nuclei of this mass chain several deficiencies remain. The identification of {sup 89}Rh isotope remains unconfirmed. The half–lives of ground states of {sup 89}Ge, {sup 89}As and {sup 89}Rh have not been measured, only the lower limits are estimated from time–of–flight in a reaction and experimental arrangement, where produced and identified. The decay schemes of {sup 89}Ge, {sup 89}As, {sup 89}Se, {sup 89}Ru and {sup 89}Rh are not known, and those for {sup 89}Tc and {sup 89}Mo are incomplete. High–lying (neutron unbound) levels in {sup 89}Kr, expected to be populated in the decay of {sup 89}Br, have not been investigated. The spins and parities for levels in {sup 89}Kr are largely unassigned, while for {sup 89}Tc and {sup 89}Ru, only few low–spin excitations are established. For {sup 89}Rb, little information is available for high–spin structures. Detailed gamma–ray data are available for {sup 88}Sr(n,γ){sup 89}Sr reaction, but most of these γ rays remain unassigned in a level scheme. Excited state data are nonexistent for {sup 89}Ge, {sup 89}As, {sup 89}Se, {sup 89}Br and {sup 89}Rh. The {sup 89}Y and {sup 89}Zr are the most extensively studied nuclei in A=89.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Comparative analysis of 11 different radioisotopes for palliative treatment of bone metastases by computational methods

Purpose: Throughout the years, the palliative treatment of bone metastases using bone seeking radiotracers has been part of the therapeutic resources used in oncology, but the choice of which bone seeking agent to use is not consensual across sites and limited data are available comparing the characteristics of each radioisotope. Computational simulation is a simple and practical method to study and to compare a variety of radioisotopes for different medical applications, including the palliative treatment of bone metastases. This study aims to evaluate and compare 11 different radioisotopes currently in use or under research for the palliative treatment of bone metastases using computational methods. Methods: Computational models were used to estimate the percentage of deoxyribonucleic acid (DNA) damage (fast Monte Carlo damage algorithm), the probability of correct DNA repair (Monte Carlo excision repair algorithm), and the radiation-induced cellular effects (virtual cell radiobiology algorithm) post-irradiation with selected particles emitted by phosphorus-32 ({sup 32}P), strontium-89 ({sup 89}Sr), yttrium-90 ({sup 90}Y ), tin-117 ({sup 117m}Sn), samarium-153 ({sup 153}Sm), holmium-166 ({sup 166}Ho), thulium-170 ({sup 170}Tm), lutetium-177 ({sup 177}Lu), rhenium-186 ({sup 186}Re), rhenium-188 ({sup 188}Re), and radium-223 ({sup 223}Ra). Results: {sup 223}Ra alpha particles, {sup 177}Lu beta minus particles, and {sup 170}Tm beta minus particles induced the highest cell death of all investigated particles and radioisotopes. The cell survival fraction measured post-irradiation with beta minus particles emitted by {sup 89}Sr and {sup 153}Sm, two of the most frequently used radionuclides in the palliative treatment of bone metastases in clinical routine practice, was higher than {sup 177}Lu beta minus particles and {sup 223}Ra alpha particles. Conclusions: {sup 223}Ra and {sup 177}Lu hold the highest potential for palliative treatment of bone metastases of all radioisotopes compared in this study. Data reported here may prompt future in vitro and in vivo experiments comparing different radionuclides for palliative treatment of bone metastases, raise the need for the careful rethinking of the current widespread clinical use of {sup 89}Sr and {sup 153}Sm, and perhaps strengthen the use of {sup 223}Ra and {sup 177}Lu in the palliative treatment of bone metastases.

60 APPLIED LIFE SCIENCES↗

Investigations of Properties of {sup 89}Y Levels with Reactor Fast Neutrons

By employing a beam of reactor fast neutrons, the spectrum of gamma rays up to an energy of 4.6MeV and their angular distributions with respect to the neutron-beamaxis aremeasured in the reaction {sup 89}Y(n, n'γ). The multipolarities and multipole-mixture parameters for 34 gamma transitions and the spin–parities J{sup π} of states excited in this reaction are determined. The lifetimes of the lowest 32 levels of 89Y were measured by the Doppler shift attenuation method, and the reduced probabilities for the respective gamma transitions were calculated. Levels of the K{sup π} = +5/2{sup +} and K{sup π} = −7/2{sup +} bands associated with, respectively, prolate and oblate deformation shapes are found in {sup 89}Y at low excitation energies.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

s-processing in AGB stars revisited. I. Does the main component constrain the neutron source in the {sup 13}C pocket?

Slow neutron captures at A ≳ 85 are mainly guaranteed by the reaction {sup 13}C(α,n){sup 16}O in asymptotic giant branch (AGB) stars, requiring proton injections from the envelope. These were so far assumed to involve a small mass (≲ 10{sup –3} M {sub ☉}), but models with rotation suggest that in such tiny layers excessive {sup 14}N hampers s-processing. Furthermore, s-element abundances in galaxies require {sup 13}C-rich layers substantially extended in mass (≳ 4 × 10{sup –3} M {sub ☉}). We therefore present new calculations aimed at clarifying those issues and at understanding whether the solar composition helps to constrain the {sup 13}C 'pocket' extension. We show that: (1) mixing 'from bottom to top' (as in magnetic buoyancy or other forced mechanisms) can form a {sup 13}C reservoir substantially larger than assumed so far, covering most of the He-rich layers; (2) on the basis of this idea, stellar models at a fixed metallicity reproduce the main s-component as accurately as before; and (3) they make nuclear contributions from unknown nucleosynthesis processes (LEPP) unnecessary, against common assumptions. These models also avoid problems of mixing at the envelope border and fulfil requirements from C-star luminosities. They yield a large production of nuclei below A = 100, so that {sup 86,} {sup 87}Sr may be fully synthesized by AGB stars, while {sup 88}Sr, {sup 89}Y, and {sup 94}Zr are contributed more efficiently than before. Finally, we suggest tests suitable for providing a final answer regarding the extension of the {sup 13}C pocket.

79 ASTRONOMY AND ASTROPHYSICS↗

Experimental studies of reactions relevant for γ-process nucleosynthesis

We report on our recent experimental studies of reactions relevant for the γ process nucleosynthesis. Applying the activation method using the Cologne Clover Counting Setup total cross sections of the reactions {sup 168}Yb(α,γ), {sup 168}Yb(α,n), and {sup 187}Re(α,n) could be obtained. Furthermore, the reaction {sup 89}Y(p,γ) was investigated via the in-beam technique with HPGe detectors at the high-efficiency g-ray spectrometer HORUS in Cologne in order to determine partial and total cross sections.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Radiative strength functions for dipole transitions in {sup 90}Zr

Partial cross sections for the (p, {gamma}) reaction on the {sup 89}Y nucleus that were measured previously at proton energies between 2.17 and 5.00 MeV and which were averaged over resonances were used to determine the absolute values and the energy distribution of the strength of dipole transitions from compound-nucleus states to low-lying levels of the {sup 90}Zr nucleus. The data obtained in this way were compared with the predictions of various models.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Elastic alpha scattering experiments and the alpha-nucleus optical potential at low energies

High precision angular distribution data of (α,α) elastic scattering are presented for the nuclei {sup 89}Y, {sup 92}Mo, {sup 106,110,116}Cd, {sup 112,124}Sn, and {sup 144}Sm at energies around the Coulomb barrier. Such data with small experimental uncertainties over the full angular range (20–170°) are the indispensable prerequisite for the extraction of local optical potentials and for the determination of the total reaction cross section σ{sub reac}. A systematic fitting procedure was applied to the experimental scattering data presented to obtain comprehensive local potential parameter sets that are composed of a real folding potential and an imaginary potential of Woods–Saxon surface type. The potential parameters obtained were used in turn to construct a new systematic α-nucleus potential with very few parameters. Although this new potential cannot reproduce the angular distributions with the same small deviations as the local potential, the new potential is able to predict the total reaction cross sections for all cases under study.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Excitation Function Calculations of Neutron-Induced Reactions of Some Zirconium Target Isotopes

Nuclear structures with high performance materials will be critical for the success of future fusion energy. Zirconium alloys are extensively used for nuclear reactor core materials as fuel cladding and guide tubes due to excellent radiation and corrosion resistant properties. In this paper, the excitation functions of {sup 90}Zr(n,2n){sup 89}Zr, {sup 90}Zr(n,α){sup 87}Sr, {sup 91}Zr(n,p){sup 91}Y and {sup 92}Zr(n,p){sup 92}Y nuclear reactions were calculated for energies up to 25 MeV. Besides, ALICE/ASH and TALYS 1.6 codes were used for the cross section calculations. The obtained calculations were compared with the experimental data in the literature.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Suppressing 1 H Spin Diffusion in Fast MAS Proton Detected Heteronuclear Correlation Solid-State NMR Experiments

Fast magic angle spinning (MAS) and indirect detection by high gyromagnetic ratio (γ) nuclei such as proton or fluorine are increasingly utilized to obtain 2D heteronuclear correlation (HETCOR) solid-state NMR spectra of spin-1/2 nuclei by using cross polarization (CP) for coherence transfer. However, one major drawback of CP HETCOR pulse sequences is that 1 H spin diffusion during the back X→ 1 H CP transfer step results in relayed correlations. This problem is particularly pronounced for the indirect detection of very low-γ nuclei such as 89 Y, 103 Rh, 109 Ag and 183 W where long contact times on the order of 10 to 30 ms are necessary for optimal CP transfer. In this work, we propose two methods that eliminate relayed correlations and allow more reliable distance information to be obtained from 2D HETCOR NMR spectra. The first method uses Lee-Goldburg (LG) CP during the X→ 1 H back-transfer step to suppress 1 H spin diffusion. We determine LG conditions compatible with fast MAS frequencies (ν rot ) of 40- 95 kHz and show that 1 H spin diffusion can be efficiently suppressed at low effective radiofrequency (RF) fields (ν 1,eff << 0.5ν rot ) and also at high effective RF fields (ν 1,eff >> 2ν rot ). We describe modified Hartmann-Hahn LG-CP match conditions compatible with fast MAS and suitable for indirect detection of moderate-γ nuclei such as 13 C, and low-γ nuclei such as 89 Y. The second method uses D-RINEPT (dipolar refocused insensitive nuclei enhanced by polarization transfer) during the X→ 1 H back-transfer step of the HETCOR pulse sequence. The effectiveness of these methods for acquiring HETCOR spectra with reduced relayed signal intensities is demonstrated with 1 H{ 13 C} HETCOR NMR experiments on L-histidine•HCl•H 2 O and 1 H{ 89 Y} HETCOR NMR experiments on an organometallic yttrium complex.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Production of Positron Emitting Radiometals: Cu-64, Y-86, Zr-89. Final report

This proposal seeks support to increase our production of the radionuclides yttrium-86 and zirconium-89 while continuing to produce copper-64. We have the advantage that we already ship out copper-64 to some 20-25 institutions per week (over 60 different institutions total including 4 Canadian sites) and thus our group already has significant experience with producing, purifying and shipping radioactive materials. A significant portion of the funds requested supported the purchase of a new hotcell for the production of zirconium-89 and yttrium-86.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗

Strong Ferromagnetic Exchange Coupling and Single-Molecule Magnetism in MoS 4 3– -Bridged Dilanthanide Complexes

We report the synthesis and characterization of the trinuclear 4d-4f compounds [Co(C 5 Me 5 ) 2 ][(C 5 Me 5 ) 2 Ln(μ-S) 2 Mo(μ-S) 2 Ln(C 5 Me 5 ) 2 ], 1-Ln (Ln = Y, Gd, Tb, Dy), containing the highly polarizable MoS 4 3 - bridging unit. UV-Vis-NIR diffuse reflectance spectra and DFT calculations of 1-Ln reveal a low-energy metal-to-metal charge transfer transition assigned to charge transfer from the singly occupied 4d z 2 orbital of Mo V to the empty 5d orbitals of the lanthanides (4d in the case of 1-Y ), mediated by sulfur-based 3p orbitals. Electron paramagnetic resonance spectra collected for 1-Y in a tetrahydrofuran solution show large 89 Y hyperfine coupling constants of A ⊥ = 23 MHz and A || = 26 MHz, indicating the presence of significant yttrium-localized unpaired electron density. Magnetic susceptibility data support similar electron delocalization and ferromagnetic Ln-Mo exchange for 1-Gd , 1-Tb , and 1-Dy . This ferromagnetic exchange gives rise to an S = 15/2 ground state for 1-Gd and one of the largest magnetic exchange constants involving Gd III observed to date, with J Gd-Mo = +16.1(2) cm -1 . Additional characterization of 1-Tb and 1-Dy by ac magnetic susceptibility measurements reveals that both compounds exhibit slow magnetic relaxation. Although a Raman magnetic relaxation process is dominant for both 1-Tb and 1-Dy , an extracted thermal relaxation barrier of U eff = 68 cm -1 for 1-Dy is the largest yet reported for a complex containing a paramagnetic 4d metal center. Furthermore, these results provide a potentially generalizable route to enhanced n d-4f magnetic exchange, revealing opportunities for the design of new n d-4f single-molecule magnets and bulk magnetic materials.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Tandem column isolation of zirconium-89 from cyclotron bombarded yttrium targets using an automated fluidic platform: Anion exchange to hydroxamate resin columns

The development of a tandem column purification method for the production of high-purity 89Zr is presented. The primary column was a macroporous strongly basic anion exchange resin on styrene divinylbenzene co-polymer. The secondary column, with an internal volume of ~27 µL, was packed with hydroxamate resin. A condition of inverted selectivity was developed, whereby the 89Zr eluent from the primary column is synonymous with the load condition on the secondary column. The ability to transfer 89Zr from one column to the next allows two sequential column clean-up methods to be performed prior to the final elution of the 89Zr. This approach assures delivery of high purity 89Zr product and assures a 89Zr product that is eluted in a substantially smaller volume than is possible when using the traditionally-employed single hydroxamate resin column method. The tandem column purification process has been implemented into a prototype automated fluidic system. The system is configured with on-line gamma detection so column effluents can be monitored in near-real time. The automated method was tested using seven cyclotron bombarded Y foil targets. It was found that 95.1±1.3% of the 89Zr present in the foils was recovered in the secondary column elution fraction. Furthermore, elution peak analysis of several 89Zr elution profile radiochromatograms made possible the determination of 89Zr recovery as a function of volume; a 89Zr product volume that contains 90% of the mean secondary column elution peak can be obtained in 0.29±0.06 mL (representing 86±5% of the 89Zr activity in the target). This product volume represents a significant increase in isotope product concentration over the predominant method used in the field. In addition to the reduced 89Zr product elution volume, titrations of the 89Zr product with deferoxamine mesylate salt across two preparatory methods resulted in mean effective specific activity (ESA) values of 279 and 340 TBq·mmole-1 and mean bindable metals concentrations ([MB]) of 13.5 and 16.7 nmole·g-1. These ESA and [MB] values infer that the 89Zr product resulting from this tandem column isolation method has the highest purity reported to date.

immunoPET, zirconium-89, laboratory automation, de↗

Improved Cumulative Fission Yield Measurements with Fission Spectrum Neutrons on 235 U

Two isotopically-characterized targets of high-purity (99.84±0.03%) 235 U-oxide and a neutron dosimetry package were exposed to a pulsed neutron irradiation using the Godiva critical assembly at the National Criticality Experiments Research Center. Following irradiation, the fissioned targets were counted with a broad-energy germanium detector. Estimates of the total fissions for each target were made using measurements of well-known fission products. The total fission values were then used to measure the fission yields of 21 fission products with half-lives between 636 and 119,700 seconds. Mean values of seventeen of the measured fission products fell within the 95% confidence level of the Evaluated Nuclear Data Files VII.1/b (ENDF/B-VII.1) using the larger of the two uncertainties: 84g Br, 89 Rb, 91 Sr, 93 Y, 97 Zr, 101 Mo, 105 Ru, 128 Sn, 129 Sb, 130g Sb, 131 Sb, 131m Te, 133 I, 135 I, 141 Ba, 142 Ba, and 142 La. Seven isotopes were measured to better precision than is listed in the ENDF/B-VII.1 database: 89 Rb, 93 Y, 128 Sn, 129 Sb, 130g Sb, 131m Te, and 133 I. Four of the measured isotopes were found to be statistically different from the ENDF/B-VII.1 database: 94 Y, 134 Te, 134 I, and 138 Xe. Two of the isotopic analyses conducted in this paper fit the parent and daughter data simultaneously. The parent-daughter pairs measured in this way were the 134 Te/I and 142 Ba/La pairs. The fission yield results obtained in this way are unique, especially for 134 I, because the parent and daughter half-lives are so close. Here, given the limited number of direct measurements of the 134 Te/I pair from fast neutron induced fission and the seemingly high estimate for 134 Te from previous work, it is likely that the value in this paper is more accurate; however, additional measurements of this pair are needed to validate this assertion.

42 ENGINEERING↗

Yttrium-90-Labeled Anti-Glypican 3 Radioimmunotherapy Halts Tumor Growth in an Orthotopic Xenograft Model of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the second most lethal malignancy globally and is increasing in incidence in the United States. Unfortunately, there are few effective systemic treatment options, particularly for disseminated disease. Glypican-3 (GPC3) is a proteoglycan cell surface receptor overexpressed in most HCCs and provides a unique target for molecular therapies. We have previously demonstrated that PET imaging using a 89 Zr-conjugated monoclonal anti-GPC3 antibody ( α GPC3) can bind to minute tumors and allow imaging with high sensitivity and specificity in an orthotopic xenograft mouse model of HCC and that serum alpha-fetoprotein (AFP) levels are highly correlated with tumor size in this model. In the present study, we conjugated 90 Y, a high-energy beta-particle-emitting radionuclide, to our α GPC3 antibody to develop a novel antibody-directed radiotherapeutic approach for HCC. Luciferase-expressing HepG2 human hepatoblastoma cells were orthotopically implanted in the livers of athymic nude mice, and tumor establishment was verified at 6 weeks after implantation by bioluminescent imaging and serum AFP concentration. Tumor burden by bioluminescence and serum AFP concentration was highly correlated in our model. Yttrium-90 was conjugated to α GPC3 using the chelating agent 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and injected via the tail vein into the experimental mice at a dose of 200 μ Ci/mouse or 300 μ Ci/mouse. Control mice received DOTA- α GPC3 without radionuclide. At 30 days after a single dose of the radioimmunotherapy agent, mean serum AFP levels in control animals increased dramatically, while animals treated with 200 μ Ci only experienced a minor increase, indicating cessation of tumor growth, and animals treated with 300 μ Ci experienced a reduction in serum AFP concentration, indicating tumor shrinkage. Mean tumor-bearing liver weight in control animals was also significantly greater than that in animals that received either dose of 90 Y- α GPC3. These results were achieved without significant toxicity as measured by body condition scoring and body weight. The results of this preclinical pilot demonstrate that GPC3 can be used as a target for radioimmunotherapy in an orthotopic mouse model of HCC and may be a target of clinical significance, particularly for disseminated HCC.

60 APPLIED LIFE SCIENCES↗

Rapid determination of radiostrontium in seawater samples

A new method for the determination of radiostrontium in seawater samples has been developed at the Savannah River National Laboratory (SRNL) that allows rapid preconcentration and separation of strontium and yttrium isotopes in seawater samples for measurement. The new SRNL method employs a novel and effective pre-concentration step that utilizes a blend of calcium phosphate with iron hydroxide to collect both strontium and yttrium rapidly from the seawater matrix with enhanced chemical yields. The pre-concentration steps, in combination with rapid Sr Resin and DGA Resin cartridge separation options using vacuum box technology, allow seawater samples up to 10 liters to be analyzed. The total 89 Sr + 90 Sr activity may be determined by gas flow proportional counting and recounted after ingrowth of 90 Y to differentiate 89 Sr from 90 Sr. Gas flow proportional counting provides a lower method detection limit than liquid scintillation or Cerenkov counting and allows simultaneous counting of samples. Simultaneous counting allows for longer count times and lower method detection limits without handling very large aliquots of seawater. Seawater samples up to 6 liters may be analyzed using Sr Resin for 89 Sr and 90 Sr with a Minimum Detectable Activity (MDA) of 1-10 mBq/L, depending on count times. Seawater samples up to 10 liters may be analyzed for 90 Sr using a DGA Resin method via collection and purification of 90 Y only. If 89 Sr and other fission products are present, then 91 Y (beta energy 1.55 MeV, 58.5 day half-life) is also likely to be present. 91 Y interferes with attempts to collect 90 Y directly from the seawater sample without initial purification of Sr isotopes first and 90 Y ingrowth. The DGA Resin option can be used to determine 90 Sr, and if 91 Y is also present, an ingrowth option with using DGA Resin again to collect 90 Y can be performed. An MDA for 90 Sr of <1 mBq/L for an 8 hour count may be obtained using 10 liter seawater sample aliquots.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗