P. Hoff

Methods for Production of Intense Beams of Unstable Nuclei: New Developments at ISOLDE

An overview of progress in the target and ion source techniques at the ISOLDE on-line mass separator is given. The production of high intensity beams of mass-separated radioactive nuclei by bombardment of targets with 600 MeV protons and 910 MeV 3He from the CERN synchro-cyclotron is discussed. Off-line tests performed in order to clarify the release properties of different target materials are described. The targets are metal powders or foils, alloys, carbides, oxides, intermetallic compounds or molten metals. The influence of reactive gases on the release rates and progress in ion-source techniques are also discussed. Recent on-line tests are described in details, and systems are suggested for the production of elements which are not yet available as primary products in on-line mass separators.

212Bi-DOTMP : An alpha particle emitting bone-seeking agent for targeted radiotherapy

The synthesis and in vivo stability of the bone-seeking alpha-particle emitting compounds 212Bi-DOTMP and 212Pb/212Bi-DOTMP are described. 212Bi-DOTMP, injected i.v. into Balb/c mice, showed prominent bone localization and a rapid clearance from blood and other organs. Femur/blood ratios increased from 13 at 15 min up to 490 at 2.0 h postinjection. Enhanced uptake of 212Bi-DOTMP was demonstrated in regions with high bone turnover. A comparison between 212Bi-DOTMP and [153Sm]Sm-EDTMP showed essentially no differences in biodistribution. 212Pb/212Bi-DOTMP followed a similar biodistribution, except for slightly elevated levels of 212Bi in the kidneys. The present study has shown 212Bi-DOTMP to be an in vivo stable bone-seeking radiopharmaceutical with promising biological properties for the treatment of sclerotic metastases and osteoblastic osteosarcoma.

223Ra for endoradiotherapeutic applications prepared from an immobilized 227Ac/227Th source

A method is described for the production of 223Ra (t1/2=11.4 d) in a quality useful for endoradiotherapeutic applications. The method is based on a long term operating generator with a source of 227Ac (t1/2=21.7 years), from which 223Ra is eluted. The 227Ac was isolated from a 231Pa source using the f-element selective extraction chromatographic material TRU-resin. The purified 227Ac/227Th source was subsequently applied to another extraction chromatographic resin, containing the extractant P,P′-di(2-ethylhexyl)methanediphosphonic acid on silica (Dipex-2) and used as a generator for 223Ra. From the generator column, the yield of 223Ra was about 60 kBq per 100 kBq of 227Ac with a highly effective separation of 223Ra from the precursors. In production runs, the activity of 227Ac was found to be 6×10-6 relative to the eluted activity of 223Ra. By using a second column of Dipex-2 for additional purification, the activity of Ac was reduced to below 7×10-8 relative to 223Ra with nearly quantitative recovery of 223Ra. The described procedure resulted in a high purity 223Ra preparation, potentially useful in, e.g., targeted radiotherapy of tumors.

Inactivation of human osteosarcoma cells in vitro by 211At-TP-3 monoclonal antibody: comparison with astatine-211-labeled bovine serum albumin, free astatine-211 and external-beam X rays.

The potential usefulness of alpha-particle radioimmunotherapy in the treatment of osteosarcoma was studied in vitro by using the monoclonal antibody TP-3 and cells of three human osteosarcoma cell lines (OHS, SAOS and KPDX) differing in antigen expression. Cell survival curves were established after treatment with (a) 211At-TP-3 of different specific activities, (b) 211At-labeled bovine serum albumin (BSA), (c) free 211At and (d) external-beam X rays. The three osteosarcoma cell lines showed similar survival curves, whether treated with external-beam X rays, 211At-BSA or free 211At. The D0s were lower for free 211At than for 211At-BSA. The survival curves for 211At-TP-3 treatment, on the other hand, differed significantly among the cell lines, suggesting that sensitivity to 211At-TP-3 treatment was governed by cellular properties other than sensitivity to external-beam X rays. The cellular property most important for sensitivity to 211At-TP-3 treatment was the antigen expression. Cell inactivation after 211At-TP-3 treatment increased substantially with increasing specific activity of the 211At-TP-3. At high specific activities, the cytotoxic effect of 211At-TP-3 was significantly higher than that of 211At-BSA. In conclusion, 211At-TP-3 has the potential to give clinically favorable therapeutic ratios in the treatment of osteosarcoma.

Evaluation of potential chelating agents for radium.

The alpha-particle-emitting radionuclide 223Ra (t(1/2) = 11.4 d) is of interest for use in targeted radionuclide therapy. In order to provide radium-labeled monoclonal antibodies, the development of a chelator binding radium in a stable fashion is required. As a part of the search for potentially useful radium chelators, the relative stability of 223Ra-chelates with linear and cyclic chelating agents was evaluated by means of competition extraction experiments.

Single-neutron states in Sn-133

The location of several single-neutron states in Sn-133 has been identified. The P-3/2, h(9/2), and f(5/2) states were found at 853.7, 1560.9, and 2004.6 keV, respectively, by measuring gamma rays in coincidence with delayed neutrons following the decay o

Recent development of high-temperature metal targets for ISOLDE

Abstract The improved target and ion-source system to be used at the SC-ISOLDE on-line mass separators is presented. Tests of a number of refractory metals with respect to their use as target materials are described. The materials discussed are pure metals and mixtures of graphite and platinum-like metals. Rapid release of a number of nuclear reaction products from powders and foils of titatium and thorium is shown. The release properties of rhenium and iridium are described. The enhanced release of refractory elements obtained from these metals by means of reaction with CF4 are related to the importance of in-grain diffusion versus surface desorption. The difference in performance between powder and foil targets is discussed. On-line tests of some of these materials combined with new high-temperature plasma-discharge type ion sources are described and the potential use of yet untested systems is discussed.

Decay Properties of 75-80Zn and Qβ-values of Neutron-Rich Zn and Ga Isotopes

The decays of strongly neutron rich isotopes of Zn have been studied with the primary aim of nuclear mass determinations. The work has also resulted in considerable information on the previously practically unknown level structure of 75,76,77,79,80Ga. Improved Qβ-values are obtained for 75,76,77,78Zn and 76,78,80Ga. The Qβ-values of 79,80Zn are reported for the first time. The experimental results are compared with predicted values of nuclear masses.

A GENERATOR FOR PRODUCTION OF 212PB AND 212BI

Abstract A generator has been developed for the production of the α-emitting radionuclide 212Bi and its parent nuclide 212Pb. The genrator is based on the emanation of 220Rn from [228Th]barium stearate. The decay product of 220Rn, 212Pb deposits on the walls of a polyethylene botlle, and can be washed off with distilled water. The generator shows no leakage of any long-lived parent nuclides, is easy to operate and has a high degree of radiation safety.

Potential in vivo generator for alpha-particle therapy with 212Bi: Presentation of a system to minimize escape of daughter nuclide after decay of 212Pb to 212Bi

Abstract Radiopharmaceuticals based on 212Pb (t1/2=10.6 h) are of interest for use as an in vivo generator of α-particle emitting 212Bi (t1/2=60.6 min). Sterically stabilized liposomes were evaluated as carriers of 212Pb/212Bi radionuclides in the reported study. 212Pb/212Bi-containing vesicles were prepared by ionophore mediated loading of 212Pb into preformed liposomes. The liposomal uptake of 212Pb with or without various concentrations of lead carrier was investigated. The retention of 212Pb and 212Bi in liposomes incubated in serum was studied. Conditions were found yielding a high and rapid uptake of 212Pb in liposomes. 90±2% of 212Pb was incorporated after 30 min. The retention of radionuclides was high, 95% of 212Pb and 212Bi were retained in liposomes after incubating for 20 h at 37°C in serum. The results from the present work indicate that an effective retention of 212Bi after the β--decay of 212Pb is achievable. This technology could be the basis of α-emitting radiopharmaceuticals built upon 212Pb.