Separation and recovery of exotic radiolanthanides from irradiated tantalum targets for half-life measurements.

The current knowledge of the half-lives (T1/2) of several radiolanthanides is either affected by a high uncertainty or is still awaiting confirmation. The scientific information deriving from this imprecise T1/2 data has a significant impact on a variety of research fields, e.g., astrophysics, fundamental nuclear sciences, and nuclear energy and safety. The main reason for these shortcomings in the nuclear databases is the limited availability of suitable sample material together with the difficulties in performing accurate activity measurements with low uncertainties. In reaction to the urgent need to improve the current nuclear databases, the long-term project "ERAWAST" (Exotic Radionuclides from Accelerator Waste for Science and Technology) was launched at Paul Scherrer Institute (PSI). In this context, we present a wet radiochemical separation procedure for the extraction and purification of dysprosium (Dy), terbium (Tb), gadolinium (Gd), and samarium (Sm) fractions from highly radioactive tantalum specimens, in order to obtain 154Dy, 157-158Tb, 148,150Gd, and 146Sm samples, needed for T1/2 determination studies. Ion-exchange chromatography was successfully applied for the separation of individual lanthanides. All separations were conducted in aqueous phase. The separation process was monitored via γ-spectrometry using suitable radioactive tracers. Both the purity and the quantification of the desired radiolanthanides were assessed by inductively coupled plasma mass spectrometry. Test experiments revealed that, prior to the Dy, Tb, Gd, and Sm separation, the removal of hafnium, lutetium, and barium from the irradiated tantalum material was necessary to minimize the overall dose rate exposure (in the mSv/h range), as well to obtain pure lanthanide fractions. With the herein proposed separation method, exotic 154Dy, 157-158Tb, 148,150Gd, and 146Sm radionuclides were obtained in sufficient amounts and purity for the preparation of samples for envisaged half-life measurements. During the separation process, fractions containing holmium, europium, and promethium radionuclides were collected and stored for further use.

Simulation of the dose rate per activity of beta-emitting radionuclides.

The dose rate per activity was simulated for 10 beta-emitting radionuclides and for different activity distributions (point source, areal sources and a semi-infinite volume source). The results are given for 7 different distances from the source (from 0.01 to 2 m) for both contributions: the beta- and electron-emission, and the X- and gamma-emission. Data are provided for both operational quantities and organ doses: Hp(0.07), Hp(3), Hp(10), Hskin and Hlens. Finally, a software applicaton to interpolate the dose rate per activity due to the beta-emission of arbitrary radionuclides is presented and a simple superposition of these data and of gamma-ray dose constants to calculate the total dose rate is described.

A chemical deposition method to prepare circular planar 147Pm sources for the measurement of particulate emission in air.

This paper describes a method for preparing a circular planar source of 17 mm diameter containing approximately 400 kBq of (147)Pm employing a wet chemical deposition technique to be used in dust monitors. This manuscript described the overall process concept and experimental procedure. The technical feasibility, efficiency of the process and product quality has been evaluated. The quality of the prepared source in terms of nonleachability, uniform distribution of activity and stability, which are necessary attributes of a radioactive source were evaluated and found to be satisfactory.

Feasibility of EBT Gafchromic films for comparison exercises among standard beta radiation fields.

The feasibility of using radiochromic films to verify the metrological coherence among standard beta radiation fields was evaluated. Exercises were done between two Brazilian metrology laboratories in beta fields from (90)Sr/(90)Y, (85)Kr and (147)Pm radiation sources. Results showed that the radiochromic film was useful for field mapping aiming uniformity and alignment verification and it was not reliable for absorbed dose measurements only for (147)Pm beta field.

(Depth-dose curves of the beta reference fields (147)Pm, (85)Kr and (90)Sr/(90)Y produced by the beta secondary standard BSS2.

The most common reference fields in beta dosimetry are the ISO 6980 series 1 radiation fields produced by the beta secondary standard BSS2 and its predecessor BSS. These reference fields require sealed beta radiation sources ((147)Pm, (85)Kr or (90)Sr/(90)Y) in combination with a source-specific beam-flattening filter, and are defined only at a given distance from the source. Every radiation sources shipped with the BSS2 is sold with a calibration certificate of the Physikalisch-Technische Bundesanstalt. The calibration workflow also comprises regular depth-dose measurements. This work publishes complete depth-dose curves of the series 1 sources (147)Pm, (85)Kr and (90)Sr/(90)Y in ICRU tissue up to a depth of 11 mm,when all electrons are stopped. For this purpose, the individual depth-dose curves of all BSS2 sources calibrated so far have been determined, i.e. the complete datasets of all BSS2 beta sources have been re-evaluated. It includes 191 depth-dose curves of 116 different sources comprising more than 2200 data points in total. Appropriate analytical representations of the nuclide-specific depth-dose curves are provided for the first time.

Comparison of two different types of LiF:Mg,Cu,P thermoluminescent dosimeters for detection of beta rays (beta-TLDs) from 90Sr/90Y, 85Kr and 147Pm sources.

Targeted radionuclide therapies in nuclear medicine departments increasingly depend on using unsealed beta radiation sources in the labeling of peptides and antibodies. Monitoring doses received by the fingers and hands during these procedures is best accomplished with TLD dosimeters that can be located at the fingertips. The present study examines the response of two TLD dosimeters (MCP-Ns and GR200A) to 90Sr/90Y, 85Kr, and 147Pm. The dosimeters were supplied by two different services, and all irradiations were performed at the PTB Institute in Germany. Each dosimetry service evaluated the dosimeters without knowledge that they had been purposefully irradiated. The accuracy and precision of the dosimeters were evaluated as a function of delivered dose, energy of beta particles and angular incidence. The results are compared to performance measures recommended by the IEC. Both dosimeter types displayed significant energy dependence. Angular dependence was moderate. Accuracy and precision as a function of dose (linearity) differed between the two systems, with the MCP-Ns being noticeably better than the GR200A. The superior precision makes the MCP-Ns much more useful for extremity dose measurements. The differences between these two dosimeter systems reinforce the need to evaluate a dosimeter carefully before using it in the daily work routine.

Efficiency of Pm-147 direct charge radioisotope battery.

A theoretical analysis is presented here of the efficiency of direct charge radioisotope batteries based on the efficiency of the radioactive source, the system geometry, electrostatic repulsion of beta particles from the collector, the secondary electron emission, and backscattered beta particles from the collector. Efficiency of various design batteries using Pm-147 sources was experimentally measured and found to be in good agreement with calculations. The present approach can be used for predicting the efficiency for different designs of direct charge radioisotope batteries.

A new approach to determine 147Pm in irradiated fuel solutions.

Developments carried out in the Laboratory of Isotopic, Nuclear and Elementary Analyses in order to quantify (147)Pm in spent nuclear fuels analyzed at the CEA within the framework of the Burn Up Credit research program for neutronic code validation are presented here. This determination is essential for safety-criticality studies. The quantity and the nature of the radionuclides in irradiated fuel solutions force us to separate the elements of interest before measuring their isotopic content by mass spectrometry. The main objective of this study is to modify the separation protocol used in our laboratory in order to recover and to measure the (147)Pm at the same time as the other lanthanides and actinides determined by mass spectrometry. A very complete study on synthetic solution (containing or not (147)Pm) was undertaken in order to determine the yield of the various stages of separation carried out before obtaining the isolated Pm fraction from the whole of the elements present in the spent fuel solutions. With the lack of natural tracer to carry out the measurement with the isotope dilution technique, the great number of isotopes in fuel, the originality of this work rests on the use of another present lanthanide in fuel to define the output of separation. The yields were measured at the conclusion of each stage of separation with two others lanthanides in order to show that one of them could be used as a tracer to correct the measurement of the (147)Pm with the separation yield. The total yield (at the conclusion of the two stages of separation) was measured at the same time by ICP-MS and liquid scintillation. This last determination made it possible to validate the use of the (147)Sm (natural) to measure the (147)Pm in ICP-MS since the outputs determined in liquid scintillation and ICP-MS (starting from the radioactive decrease of the source having been used to make the synthetic solution) were equivalent. It is the first time that such measurement is performed in ICP-MS. The measurement of the (147)Pm was finally taken on fuels UOx and MOx by using the (153)Eu like a tracer of the separation yield. The results obtained are in very good agreement with those obtained from neutronic calculation code.

Comparative biokinetics of trivalent radionuclides with similar ionic dimensions: promethium-147, curium-242 and americium-241.

Data on the distribution and redistribution patterns in the laboratory rat of three trivalent elements with a similar ionic radius have been compared. This showed that these distributions for the two ions with the same ionic radius (111 pm), i.e., those of promethium (a lanthanoid) and curium (an actinoid), were indistinguishable and that americium, with a slightly larger ion size (111.5 pm), behaved similarly. The results are consistent with the suggestion that ion size is the only important factor controlling the deposition and redistribution patterns of trivalent lanthanoids and actinoids in rats. The result is important because it suggests that the same radiological protection dosimetry models should be used for trivalent actinoids and lanthanoids, that human volunteer data generated for lanthanoid isotopes can be used to predict the behavior of actinoids with the same ion size, and that appropriate pairs of beta-particle-emitting lanthanoid and alpha-particle-emitting actinoids could be used to study the relative toxicity of alpha and beta particles in experimental animals.

Electron- and positron-emitting radiolanthanides for therapy: aspects of dosimetry and production.

UNLABELLED: All lanthanides have similar chemical properties regarding labeling. Therefore, radiolanthanides that have been used for therapy, such as (153)Sm and (177)Lu, might easily be replaced with other radiolanthanides. The aim of this work was to investigate the suitability of electron- and positron-emitting radiolanthanides for radionuclide therapy with reference to dosimetry and production possibilities. METHODS: Radiolanthanides with half-lives of 1 h to 15 d, stable or long-lived daughters, and limited photon emission were selected. The ratio of the absorbed dose rate to the tumors and the normal tissue (TND) was calculated for different tumor sizes and compared with the TND values for (90)Y and (131)I. The normal tissue and tumors were simulated as an ellipsoid and spheres, respectively. The TND values depend on the physical parameters of the radionuclides, the tumor size, and the ratio between the activity concentrations in the tumor and normal tissue (TNC). RESULTS: (153)Sm, (161)Tb, (169)Er, (175)Yb, and (177)Lu had the highest TND values for most of the tumor sizes studied. Among these radiolanthanides, (161)Tb and (177)Lu are the only ones that can be produced no-carrier-added (nca) and with high specific activities. The Auger-electron emitters (161)Ho and (167)Tm had high TND values for tumors weighing less than 1 mg and can be produced nca and with high specific activities. (142)Pr, (145)Pr, and (166)Ho showed TND values similar to those of (90)Y. (166)Ho is generator produced and can be obtained nca and at high specific activities. (143)Pr, (149)Pm, (150)Eu, (159)Gd, (165)Dy, (176m)Lu, and (179)Lu had higher TND values than did (90)Y for all tumor sizes studied, but only (149)Pm can be produced nca and at high specific activities. The other electron-emitting radiolanthanides and the positron-emitting radiolanthanides showed low TND values for all tumor sizes because of the high photon contribution. CONCLUSION: The low-energy electron emitters (161)Tb, (177)Lu, and (167)Tm might be suitable for radionuclide therapy. The Auger-electron emitter (161)Ho might not be suitable for systemic radionuclide therapy (intravenous injection) because of its short half-life but might be suitable for local therapy (e.g., in body cavities). If higher electron energy is needed, (149)Pm or (166)Ho might be suitable for radionuclide therapy.

Radiolanthanide-labeled monoclonal antibody CC49 for radioimmunotherapy of cancer: biological comparison of DOTA conjugates and 149Pm, 166Ho, and 177Lu.

The radiolanthanides 149Pm, 166Ho, and 177Lu have decay characteristics suitable for radioimmunotherapy (RIT) of cancer. N-Hydroxysulfosuccinimidyl DOTA (DOTA-OSSu) and methoxy-DOTA (MeO-DOTA) were conjugated to the anti-TAG-72 monoclonal antibody CC49 for radiolabeling with 149Pm, 166Ho, and 177Lu. While both DOTA conjugates could be labeled to high specific activity with 177Lu, MeO-DOTA afforded superior conjugate stability, radiolabeling, and radiochemical purity. Pilot biodistributions in nude mice bearing LS174T human colon carcinoma xenografts demonstrated that MeO-DOTA afforded higher tumor uptake and lower kidney retention of 177Lu than DOTA-OSSu. The in vitro stability of 149Pm-, 166Ho-, and 177Lu-MeO-DOTA-CC49 was evaluated using serum and hydroxyapatite assays. Serum stability of radiolanthanide-labeled MeO-DOTA-CC49 followed a trend based on the coordination energies of the radiometals, with 177Lu showing the highest stability after 96 to 168 h at 37 C. In contrast, MeO-DOTA-CC49 labeled with all three radiolanthanides was >92% stable to hydroxyapatite challenge for 168 h at 37 C. Comprehensive biodistributions of 149Pm-, 166Ho-, and 177Lu-MeO-DOTA-CC49 were obtained in LS174T-bearing nude mice. Maximum tumor uptakes were 100.0% ID/g for 149Pm at 96 h, 69.5% ID/g for 166Ho at 96 h, and 132.4% ID/g for 177Lu at 168 h. Normal organ uptakes were generally low, except in the liver, spleen, and kidney at early time points. By 96 to 168 h postinjection, nontarget organ uptake decreased to approximately 7% ID/g (kidney), 12% ID/g (spleen), and 20% ID/g (liver) for each radiolanthanide. When labeled with 149Pm, 166Ho, and 177Lu, MeO-DOTA-CC49 has potential for RIT of colorectal cancer and other carcinomas.

Evaluation of beta-absorbed fractions in a mouse model for 90Y, 188Re, 166Ho, 149Pm, 64Cu, and 177Lu radionuclides.

Several short-lived, high-energy beta emitters are being proposed as the radionuclide components for molecular- targeted potential cancer therapeutic agents. The laboratory mice used to determine the efficacy of these new agents have organs that are relatively small compared to the ranges of these high-energy particles. The dosimetry model developed by Hui et al. was extended to provide realistic beta-dose estimates for organs in mice that received therapeutic radiopharmaceuticals containing (90)Y, (188)Re, (166)Ho, (149)Pm, (64)Cu, and (177)Lu. Major organs in this model included the liver, spleen, kidneys, lungs, heart, stomach, small and large bowel, thyroid, pancreas, bone, marrow, carcass, and a 0.025-g tumor. The study as reported in this paper verifies their results for (90)Y and extends them by using their organ geometry factors combined with newly calculated organ self-absorbed fractions from PEREGRINE and MCNP. PEREGRINE and MCNP agree to within 8% for the worst-case organ with average differences (averaged over all organs) decreasing from 5% for (90)Y to 1% for (177)Lu. When used with typical biodistribution data, the three different models predict doses that are in agreement to within 5% for the worst-case organ. The beta-absorbed fractions and cross-organ-deposited energy provided in this paper can be used by researchers to predict mouse-organ doses and should contribute to an improved understanding of the relationship between dose and radiation toxicity in mouse models where use of these isotopes is favorable.

Design and coordination behavior of the first selective recognition ligand of 147Pm(III).

A new amide tripodal ligand, 6-[2-(2-diethylamino-2-oxoethoxy)ethyl]-N,N,12-triethyl-11-oxo-3,9-dioxa-6,12-diazatetradecanamide (4) has been designed and synthesized for the recognition of rare earth ions. Three representative complexes of trivalent lighter (La), middle (Gd), and heavier (Er) rare earth ions with 4 were synthesized and characterized by X-ray crystallography. In the complex, the heptadentate forms a cup-like coordination cavity encapsulating the central ion. Different supramolecular complex dimers are constructed by pi-pi interaction and van der Waals forces in accordance with the lanthanide contraction. The differences of the cavity and dimer structures were investigated further by assessing the separation efficiency of in multitrace solvent extraction of rare earth ions from picrate acid solution and the ligand has the best separation factor for 147Pm(III).

Biological comparison of 149Pm-, 166Ho-, and 177Lu-DOTA-biotin pretargeted by CC49 scFv-streptavidin fusion protein in xenograft-bearing nude mice.

The radiolanthanides (149)Pm, (166)Ho, and (177)Lu possess a range of half-lives and alpha(-) beta(-) energies for targeted radiotherapy of cancer. (149)Pm-, (166)Ho-, and (177)Lu-DOTA-biotin were pretargeted to LS174T colorectal tumors in nude mice with CC49 scFvSA antibody-streptavidin fusion protein. Tumor uptakes of (149)Pm (22.9% ID/g), (166)Ho (30.2% ID/g), and (177)Lu (35.4% ID/g) peaked at 1-4 h. Rapid blood disappearance was accompanied by urinary excretion of 59-66% ID within 1 h. Biodistributions of these agents show promise for pretargeted radioimmunotherapy of cancer.

Aminocarboxylate complexes and octreotide complexes with no carrier added 177Lu, 166Ho and 149Pm.

Several aminocarboxylate complexes of the "no carrier added" (NCA) radiolanthanides (149)Pm, (166)Ho and (177)Lu were evaluated using our in vitro hydroxyapatite and serum stability model and in vivo in normal CF-1 mice [10]. The aminocarboxylate chelates evaluated with the NCA radiolanthanides for in vitro stability were EDTA, CDTA, DTPA, MA-DTPA and DOTA. In addition, the NCA radiolanthanide complexes with DTPA-octreotide (DTPA-OCT) were synthesized and evaluated, as a model for a peptide conjugated aminocarboxylate complex. The biodistribution studies of the NCA complexes with DTPA, DOTA and DTPA-OCT showed that the in vitro model correctly predicted the in vivo stability of the radiolanthanide complexes, with Ln-DOTA > Ln-DTPA > Ln-DTPA-OCT.

Pm-149 DOTA bombesin analogs for potential radiotherapy. in vivo comparison with Sm-153 and Lu-177 labeled DO3A-amide-betaAla-BBN(7-14)NH(2).

Promethium-149 (149Pm) is one of only three radiolanthanides that can be prepared in no carrier added concentrations. This high specific activity radiolanthanide is thus suitable for targeting limited numbers of specific receptors found on many tumor cells. Promethium-149 is a moderate energy beta(-) emitter (1.07 MeV (95.9%)) with a half-life of 2.21 days. Pm-149 also emits a low abundance of an imageable gamma ray (286 keV (3%)) that may allow in vivo tracking of the therapeutic dose. The 149Pm and Sm complexes with the DO3A-amide chelator with zero and three carbon spacers to the bombesin peptide analog BBN(7-14)NH(2) were synthesized and characterized. The Sm complexes were synthesized for macroscopic characterization purposes (ESI-MS, in vitro cell binding) since no stable isotopes of Pm are known. The biological properties of the 149Pm, 153Sm and 177Lu-DO3A-amide-betaAla-BBN complexes were compared in normal mouse biodistribution studies.

Direct determination of 90Sr and 147Pm in Chernobyl hot particles collected in Kiev using beta absorption method.

59 hot particles were collected in Kiev, Ukraine, in 1987. All but one were prepared from a moss carpet of 360 cm2 area. Radionuclide composition of the hot particles was investigated by gamma-spectrometry and beta absorption method. Pure beta emitters 90Sr and 147Pm were determined in 25 hot particles measuring the beta absorption curves of the hot particles with an end-window Geiger-Müller counter and decomposing the curves in order to obtain the contributions of 90Sr and 147Pm to the total beta counting rate. All but one of the hot particles were found to be the debris of the fuel. The activity ratio 90Sr:l44Ce was 0.052 in good agreement with theoretical calculations on core inventories. This means that strontium behaved as a nonvolatile element in the process of the formation of the hot particles investigated. The activity ratio 147Pm:144Ce was 0.078 which is half of the theoretical result. Although 147Pm is considered to be a refractory nuclide, it seems that significant part of 147Pm went to the homogeneous fraction of the general fallout. The surface density of hot particles (of higher than about 50 Bq activity) was about 1,600 m(-2) and that of the activities of the nuclides 90Sr, 106Ru, 134Cs, 137Cs, 144Ce and 147Pm as components of hot particles was 12.2, 54.3, 5.9, 9.7, 234 and 18.3 kBq m(-2) (activity values counted for 26 April 1986), respectively, in downtown Kiev city in 1987.

Beta-ray photography of lyophilized animal sections.

A new photographic method that images the density distribution of lyophilized animal sections approximately 50 microns in thickness is described. The new method involves sandwiching the animal section between a radiation sensor and a 147Pm planar radiation source. Either conventional photographic film or an imaging plate for radioluminography can be used as the sensor. The method described herein will find promising applications in whole body autoradiography as well as in the study of osteoporosis in experimental animals.

A Monte Carlo approach to assessing 147Pm in the liver of the adult phantom.

A low-background phoswich detector is used to detect small amounts of 147Pm--a pure beta-emitting nuclide--present in the liver of an occupational worker. The assessment was based on the measurement of bremsstrahlung radiation produced by the beta particles in the tissue. Computer programs based on Monte Carlo techniques for photon transport have been developed to calculate the response of an external phoswich detector to 1) a 147Pm point source embedded in tissue-equivalent slabs of various thicknesses; and 2) various source distributions of 147Pm in the liver of an adult phantom. The goal is to theoretically calibrate the phoswich detector for each source distribution and to study the variation of maxima of the spectra with the depth of the source in the adult phantom liver and tissue-equivalent slabs. The initial bremsstrahlung photon distribution of 147Pm in water has been computed using Wyard's and Pratt's methods. These calculations have been compared with experimental measurements using Perspex acrylic sheet slabs. Good agreements have been noted when the initial bremsstrahlung spectrum is obtained by using Wyard's method. These results find applications in monitoring the liver burdens in occupational workers handling 147Pm-based radioluminous paints.

High-resolution determination of 147Pm in urine using dynamic ion-exchange chromatography.

A procedure has been developed for measuring 147Pm in bioassay samples, based on the separation and preconcentration of 147Pm from the urine matrix by adsorption onto a conventional cation-exchange column with final separation and purification by HPLC using dynamic ion-exchange chromatography. The concentration of 147Pm is determined by collecting the appropriate HPLC fraction and measuring the 147Pm by liquid scintillation counting. The limit of detection is 0.1 Bq (3 fg) 147Pm based on a 500-mL sample of urine and a counting time of 30 min with a background of 100 cpm. Ten samples can be processed in 1.5-2 days.