F.M. Nortier

Charged-Particle Cross Section Database for Medical Radioisotope Production

Charged-particle cross section database for medical radioisotope production was developed under an international project coordinated by the IAEA. The project focused on radioisotopes for diagnostic purposes and on the related beam monitor reactions. The database contains activation cross-sections of reactions induced by light charged particles with energies mostly up to about 40 MeV. It includes 22 beam monitor reactions for protons (8), deuterons (5), 3He (3) and α-particles (6), and 26 reactions for most commonly used γ-emitters (12), their serious isotopic impurities (4) and β+-emitters (10).

Excitation functions of 125Te(p, xn)-reactions from their respective thresholds up to 100 MeV with special reference to the production of 124I.

Excitation functions of the nuclear reactions 125Te(p, xn) (119,120m, 120g, 121,122,123,124,125)I were measured for the first time from their respective thresholds up to 100 MeV using the stacked-foil technique. Thin samples were prepared by electrolytic deposition of 98.3% enriched 125Te on Ti-backing. In addition to experimental studies, excitation functions were calculated by the modified hybrid model code ALICE-IPPE. The experimental and theoretical data generally showed good agreement. From the measured cross section data, integral yields of (123,124,125)I were calculated. The energy range Ep 21 --> 15 MeV appears to be very suitable for the production of the medically interesting radionuclide 124I (T(1/2) = 4.18 d; I(beta)+ = 25%). The thick target yield of 124I amounts to 81 MBq/microA h and the level of 125I-impurity to 0.9%. The 125Te(p,2n)124I reaction gives 124I yield about four times higher than the commonly used 124Te(p,n)124I and 124Te(d,2n)124I reactions. The proposed production energy range is too high for small cyclotrons but large quantities of 124I can be produced with medium-sized commercial machines.

Application of ion exchange and extraction chromatography to the separation of actinium from proton-irradiated thorium metal for analytical purposes

Actinium-225 (t1/2=9.92d) is an α-emitting radionuclide with nuclear properties well-suited for use in targeted alpha therapy (TAT), a powerful treatment method for malignant tumors. Actinium-225 can also be utilized as a generator for (213)Bi (t1/2 45.6 min), which is another valuable candidate for TAT. Actinium-225 can be produced via proton irradiation of thorium metal; however, long-lived (227)Ac (t1/2=21.8a, 99% β(-), 1% α) is co-produced during this process and will impact the quality of the final product. Thus, accurate assays are needed to determine the (225)Ac/(227)Ac ratio, which is dependent on beam energy, irradiation time and target design. Accurate actinium assays, in turn, require efficient separation of actinium isotopes from both the Th matrix and highly radioactive activation by-products, especially radiolanthanides formed from proton-induced fission. In this study, we introduce a novel, selective chromatographic technique for the recovery and purification of actinium isotopes from irradiated Th matrices. A two-step sequence of cation exchange and extraction chromatography was implemented. Radiolanthanides were quantitatively removed from Ac, and no non-Ac radionuclidic impurities were detected in the final Ac fraction. An (225)Ac spike added prior to separation was recovered at ≥ 98%, and Ac decontamination from Th was found to be ≥ 10(6). The purified actinium fraction allowed for highly accurate (227)Ac determination at analytical scales, i.e., at (227)Ac activities of 1-100 kBq (27 nCi to 2.7 μCi).

Proton-induced cross sections relevant to production of 225Ac and 223Ra in natural thorium targets below 200 MeV

Cross sections for (223,)(225)Ra, (225)Ac and (227)Th production by the proton bombardment of natural thorium targets were measured at proton energies below 200 MeV. Our measurements are in good agreement with previously published data and offer a complete excitation function for (223,)(225)Ra in the energy range above 90 MeV. Comparison of theoretical predictions with the experimental data shows reasonable-to-good agreement. Results indicate that accelerator-based production of (225)Ac and (223)Ra below 200 MeV is a viable production method.

Excitation functions of 85Rb(p, xn)85m, g, 83,82,81Sr reactions up to 100 MeV: integral tests of cross section data, comparison of production routes of 83Sr and thick target yield of 82Sr

The beta+ emitter 83Sr (T(1/2) = 32.4 h, Ebeta+ = 1.23 MeV, Ibeta+ = 24%) is a potentially useful radionuclide for therapy planning prior to the use of the beta+ emitter 89Sr (T(1/2) = 50.5 d). In order to investigate its production possibility, cross section measurements on the 85Rb(p,xn)-reactions, leading to the formation of the isotopes (85m,g)Sr, 83Sr, 82Sr and 81Sr, were carried out using the stacked-foil technique. In a few cases, the products were separated via high-performance liquid chromatography. For 82Sr, both gamma-ray and X-ray spectrometry were applied; in other cases only gamma-ray spectrometry was used. From the measured excitation functions, the expected yields were calculated. For the energy range Ep = 37 --> 30 MeV the 83Sr yield amounts to 160 MBq/microA h and the level of the 85gSr (T(1,2) = 64.9 d) and 82Sr (T(1/2) = 25.5 d) impurities to <0.25%. In integral tests involving yield measurements radiostrontium was chemically separated and its radioactivity determined. The experimental production data agreed within 10% with those deduced from the excitation functions. The results of the 85Rb(p,3n)83Sr reaction were compared with the data on the production of 83Sr via the 82Kr(3He,2n)-process. In the energy range E3Hc = 18 --> 10 MeV the theoretical yield of 83Sr amounts to 5 MBq/microA h and the 82Sr impurity to about 0.2%. The method of choice for the production of 83Sr is thus the 85Rb(p,3n)-process, provided a 40 MeV cyclotron is available. During this study some supplementary information on the yield and purity of 82Sr was also obtained.

225Ac and 223Ra production via 800 MeV proton irradiation of natural thorium targets

Cross sections for the formation of (225,227)Ac, (223,225)Ra, and (227)Th via the proton bombardment of natural thorium targets were measured at a nominal proton energy of 800 MeV. No earlier experimental cross section data for the production of (223,225)Ra, (227)Ac and (227)Th by this method were found in the literature. A comparison of theoretical predictions with the experimental data shows agreement within a factor of two. Results indicate that accelerator-based production of (225)Ac and (223)Ra is a viable production method.

Some nuclear chemical aspects of medical generator nuclide production at the Los Alamos hot cell facility

Abstract Generator nuclides constitute a convenient tool for applications in nuclear medicine. In this paper, some radiochemical aspects of generator nuclide parents regularly processed at Los Alamos are introduced. The bulk production of the parent nuclides 68Ge, 82Sr, 109Cd and 88Zr using charged particle beams is discussed. Production nuclear reactions for these radioisotopes, and chemical separation procedures are presented. Experimental processing yields correspond to 80%-98% of the theoretical thick target yield. Reaction cross sections are modeled using the code ALICE-IPPE; it is observed that the model largely disagrees with experimental values for the nuclear processes treated. Radionuclide production batches are prepared 1-6 times yearly for sales. Batch activities range from 40 MBq to 75 GBq.

Proton irradiation parameters and chemical separation procedure for the bulk production of high-specific-activity 186gRe using WO3 targets

Abstract Rhenium-186g (T1/2= 89.2 h) is a β− emitter suitable for therapeutic applications. Current production methods rely on reactor production via 185Re(n,γ) which results in low specific activities, thereby limiting its use. Production by p,d activation of enriched 186W results in a 186gRe product with a higher specific activity, allowing it to be used for targeted therapy with limited receptors. A test target consisting of pressed, sintered natWO3 was proton irradiated at Los Alamos (LANL-IPF) to evaluate product yield and impurities, irradiation parameters and wet chemical Re recovery for proof-of-concept for bulk production of 186gRe. We demonstrated isolation of 186gRe in 97% yield from irradiated natWO3 targets within 12 h of end of bombardment (EOB) via an alkaline dissolution followed by anion exchange. The recovery process has potential for automation, and WO3 can be easily recycled for recurrent irradiations. A 186gRe batch yield of 42.7 ± 2.2 μCi/μAh or 439 ± 23 MBq/C was obtained after 24 h in an 18.5 μA proton beam. The target entrance energy was determined to be 15.6 MeV. The specific activity of 186gRe at EOB was measured to be 1.9 kCi (70.3 TBq) mmol−1, which agrees well with the result of a previous 185,186mRe co-production EMPIRE and TALYS modeling study assuming similar conditions. Utilizing enriched 186WO3, we anticipate that a proton beam of 250 μA for 24 h will provide batch yields of 256 mCi (9.5 GBq) of 186gRe at EOB with specific activities even higher than 1.9 kCi (70.3 TBq) mmol−1, suitable for therapy applications.

Ac, La, and Ce radioimpurities in 225Ac produced in 40–200 MeV proton irradiations of thorium

Abstract Accelerator production of 225Ac addresses the global supply deficiency currently inhibiting clinical trials from establishing 225Acs therapeutic utility, provided that the accelerator product is of sufficient radionuclidic purity for patient use. Two proton activation experiments utilizing the stacked foil technique between 40 and 200 MeV were employed to study the likely co-formation of radionuclides expected to be especially challenging to separate from 225Ac. Foils were assayed by nondestructive γ-spectroscopy and by α-spectroscopy of chemically processed target material. Nuclear formation cross sections for the radionuclides 226Ac and 227Ac as well as lower lanthanide radioisotopes 139Ce, 141Ce, 143Ce, and 140La whose elemental ionic radii closely match that of actinium were measured and are reported. The predictions of the latest MCNP6 event generators are compared with measured data, as they permit estimation of the formation rates of other radionuclides whose decay emissions are not clearly discerned in the complex spectra collected from 232Th(p,x) fission product mixtures.

Cross sections from proton irradiation of thorium at 800 MeV

Nuclear formation cross sections are reported for 65 nuclides produced from 800-MeV proton irradiation of thorium foils. These data are useful as benchmarks for computational predictions in the ongoing process of theoretical code development and also to the design of spallation-based radioisotope production currently being considered for multiple radiotherapeutic pharmaceutical agents. Measured data are compared with the predictions of three MCNP6 event generators and used to evaluate the potential for 800-MeV productions of radioisotopes of interest for medical radiotherapy. In only a few instances code predictions are discrepant from measured values by more than a factor of two, demonstrating satisfactory predictive power across a large mass range. Similarly, agreement between measurements presented here and those previously reported is good, lending credibility to predictions of target yields and radioimpurities for high-energy accelerator-produced radionuclides.