ISOLDE Facility Research Articles

Preclinical investigations and first-in-human application of 152Tb-PSMA-617 for PET/CT imaging of prostate cancer

BackgroundFor almost a decade, terbium radioisotopes have been explored for their potential theragnostic application in nuclear medicine: 152Tb and 155Tb are the radioisotopes identified for PET or SPECT imaging, while 149Tb and 161Tb have suitable decay characteristics for α- and combined β−/Auger-e−-therapy, respectively. In the present study, the application of 152Tb, in combination with PSMA-617 for imaging of prostate-specific membrane antigen (PSMA)-positive prostate cancer, was demonstrated in a preclinical setting and in a patient with metastatic castration-resistant prostate cancer (mCRPC).Results152Tb was produced at the ISOLDE facility at CERN/Geneva, Switzerland, by spallation, followed by on-line mass separation. The chemical separation was performed at Paul Scherrer Institute using chromatographic methods, as previously reported. 152Tb was employed for labeling PSMA-617, and the radioligand was extensively investigated in vitro to demonstrate similar characteristics to its 177Lu-labeled counterpart. Preclinical PET/CT imaging studies performed with mice enabled visualization of PSMA-positive PC-3 PIP tumors, while uptake in PSMA-negative PC-3 flu tumors were absent. Based on these promising preclinical results, 152Tb was shipped to Zentralklinik Bad Berka, Germany, where it was used for labeling of PSMA-617, enabling PET imaging of a patient with mCRPC. PET/CT scans were performed over a period of 25 h post injection (p.i.) of the radioligand (140 MBq). The images were of diagnostic quality, particularly those acquired at later time points, and enabled the detection of the same metastatic lesions and of local recurrent tumor as previously detected by 68Ga-PSMA-11 PET/CT acquired 45 min p.i.ConclusionsThe results of this study demonstrate the successful preparation and preclinical testing of 152Tb-PSMA-617 and its first application in a patient with mCRPC. This work could pave the way towards clinical application of other Tb radionuclides in the near future, most importantly 161Tb, which has promising decay characteristics for an effective treatment of mCRPC patients.

Mass measurements of neutron-rich isotopes near N=20 by in-trap decay with the ISOLTRAP spectrometer

The masses of $^{34}\mathrm{Si}$, $^{33,34}\mathrm{Mg}$, and $^{34}\mathrm{Al}$ have been measured with the ISOLTRAP Penning-trap spectrometer at ISOLDE/CERN. The results are in agreement with previous mass measurements and uncertainties have been decreased. The mass of $^{34}\mathrm{Al}$ was determined in two configurations, one following direct production by the ISOLDE facility, favoring the ${4}^{\ensuremath{-}}$ state, expected to be the ground state, second by in-trap decay of $^{34}\mathrm{Mg}$, followed by recoil-ion trapping, favoring the production of the isomeric ${1}^{+}$ state. A position-sensitive detector was used to clean the ToF-ICR resonance. In addition, the mass of the refractory doubly magic $^{34}\mathrm{Si}$ nucleus was directly measured, using the in-trap decay of $^{34}\mathrm{Mg}$, following two sequential recoil-ion captures. The approach, challenges and conclusions are discussed.

β decay of In133 : γ emission from neutron-unbound states in Sn133

Excited states in Sn-133 were investigated through the beta decay of In-133 at the ISOLDE facility. The ISOLDE Resonance Ionization Laser Ion Source (RILIS) provided isomer-selective ionization for In-133, allowing us to study separately, and in detail, the beta-decay branch of In-133 J(pi)= (9/2(+)) ground state and its J(pi) = (1/2(-)) isomer.Thanks to the large spin difference of the two beta-decaying states of In-133, it is possible to investigate separately the lower and higher spin states in the daughter, Sn-133, and thus to probe independently different single-particle and single-hole levels. We report here new gamma transitions observed in the decay of In-133, including those assigned to the deexcitation of the neutron-unbound states.

^{7}Be(n,p)^{7}Li Reaction and the Cosmological Lithium Problem: Measurement of the Cross Section in a Wide Energy Range at n_TOF at CERN.

We report on the measurement of the ^{7}Be(n,p)^{7}Li cross section from thermal to approximately 325keV neutron energy, performed in the high-flux experimental area (EAR2) of the n_TOF facility at CERN. This reaction plays a key role in the lithium yield of the big bang nucleosynthesis (BBN) for standard cosmology. The only two previous time-of-flight measurements performed on this reaction did not cover the energy window of interest for BBN, and they showed a large discrepancy between each other. The measurement was performed with a Si telescope and a high-purity sample produced by implantation of a ^{7}Be ion beam at the ISOLDE facility at CERN. While a significantly higher cross section is found at low energy, relative to current evaluations, in the region of BBN interest, the present results are consistent with the values inferred from the time-reversal ^{7}Li(p,n)^{7}Be reaction, thus yielding only a relatively minor improvement on the so-called cosmological lithium problem. The relevance of these results on the near-threshold neutron production in the p+^{7}Li reaction is also discussed.

Precision Mass Measurements of ^{58-63}Cr: Nuclear Collectivity Towards the N=40 Island of Inversion.

The neutron-rich isotopes ^{58-63}Cr were produced for the first time at the ISOLDE facility and their masses were measured with the ISOLTRAP spectrometer. The new values are up to 300 times more precise than those in the literature and indicate significantly different nuclear structure from the new mass-surface trend. A gradual onset of deformation is found in this proton and neutron midshell region, which is a gateway to the second island of inversion around N=40. In addition to comparisons with density-functional theory and large-scale shell-model calculations, we present predictions from the valence-space formulation of the abinitio in-medium similarity renormalization group, the first such results for open-shell chromium isotopes.

Gamma-ray branching ratios in the decay of 49Cr

The $\gamma$ -decay branching ratios of 49V have been studied in the $\beta$ /EC decay of 49Cr. The $\gamma$ -ray spectrum has been measured with a 70% relative efficiency co-axial germanium detector calibrated in efficiency with a precision of about 0.5%. The primary result is the measurement of the relative branching ratios of the three main $\gamma$ rays in the decay of 49Cr. Large discrepancies were found with a previous experimental work. The 49Cr sample was produced by proton impact on a ZrO2 target and collected at the ISOLDE facility of CERN and enabled us to re-evaluate the decay scheme of 49Cr. The new data allow the use of this nucleus for future high-precision calibration work.

Laser-spectroscopy studies of the nuclear structure of neutron-rich radium

The neutron-rich radium isotopes, Ra222−233, were measured with Collinear Resonance Ionization Spectroscopy (CRIS) at the ISOLDE facility, CERN. The hyperfine structure of the 7s2S01→7s7pP13 transition was probed, allowing measurement of the magnetic moments, quadrupole moments, and changes in mean-square charge radii. These results are compared to existing literature values, and the new moments and change in mean-square charge radii of Ra231 are presented. Low-resolution laser spectroscopy of the very neutron-rich Ra233 has allowed the isotope shift and relative charge radius to be determined for the first time.

Probing the Ga31 ground-state properties in the region near Z=28 with high-resolution laser spectroscopy

Magnetic-dipole and electric-quadrupole moments for $^{65,67,69,75,79\text{--}82}\mathrm{Ga}$ are reported using the Collinear Resonance Ionization Spectroscopy (CRIS) technique at the ISOLDE facility, CERN. The moments of $^{65}\mathrm{Ga}$ have been measured for the first time: $\ensuremath{\mu}=+1.775(3)\phantom{\rule{4pt}{0ex}}{\ensuremath{\mu}}_{\mathrm{N}}$ and ${Q}_{s}=+21.0(15)\phantom{\rule{4pt}{0ex}}e\phantom{\rule{0.16em}{0ex}}{\mathrm{fm}}^{2}$. These results are compared to shell-model calculations using the GXPF1 and JUN45 interactions and the trends of the moments approaching the region of the doubly magic $^{56}\mathrm{Ni}$ are discussed. Additionally, new values for the change in mean-square charge radii for $^{65}\mathrm{Ga}$ and $^{67}\mathrm{Ga}$ allow investigation into the odd-even staggering in the region below $N=40$.

Fast-timing spectroscopy at ISOLDE

The advanced time-delayed (t) method has been used at ISOLDE since the relocation of the facility from the synchrocyclotron to the CERN proton synchrotron booster, a quarter of a century ago. The method was designed for precision measurements with low-intensity beams, achieving good efficiency and excellent time resolution with a compact setup. Over this time the technique has evolved to cope with the challenge of measuring lifetimes of complex level schemes of increasingly exotic nuclei populated in β decay. The ISOLDE facility provides unsurpassed opportunities to study many regions of the nuclide chart. The physics case encompasses topics of interest across the nuclide chart, including the evolution of shell structure around neutron shell and subshell closures such as N = 20, N = 40 and N = 50, shape coexistence, and octupole correlations in heavy nuclei. The recently commissioned ISOLDE decay station provides enhanced capabilities that will be fully exploited with the increased beam intensities available at the upcoming HIE-ISOLDE facility.

The ISOLDE facility

The ISOLDE facility has undergone numerous changes over the last 17 years driven by both the physics and technical community with a common goal to improve on beam variety, beam quality and safety. Improvements have been made in civil engineering and operational equipment while continuing developments aim to ensure operations following a potential increase in primary beam intensity and energy. This paper outlines the principal technical changes incurred at ISOLDE by building on a similar publication of the facility upgrades by Kugler (2000 Hyperfine Interact. 129 23–42). It also provides an insight into future perspectives through a brief summary issues addressed in the HIE-ISOLDE design study Catherall et al (2013 Nucl. Instrum. Methods Phys. Res. B 317 204–207).

Ion beam production and study of radioactive isotopes with the laser ion source at ISOLDE**This article belongs to the Focus on Exotic Beams at ISOLDE: A Laboratory Portrait special issue.

At ISOLDE the majority of radioactive ion beams are produced using the resonance ionization laser ion source (RILIS). This ion source is based on resonant excitation of atomic transitions by wavelength tunable laser radiation. Since its installation at the ISOLDE facility in 1994, the RILIS laser setup has been developed into a versatile remotely operated laser system comprising state-of–the-art solid state and dye lasers capable of generating multiple high quality laser beams at any wavelength in the range of 210–950 nm. A continuous programme of atomic ionization scheme development at CERN and at other laboratories has gradually increased the number of RILIS-ionized elements. At present, isotopes of 40 different elements have been selectively laser-ionized by the ISOLDE RILIS. Studies related to the optimization of the laser–atom interaction environment have yielded new laser ion source types: the laser ion source and trap and the versatile arc discharge and laser ion source. Depending on the specific experimental requirements for beam purity or versatility to switch between different ionization mechanisms, these may offer a favourable alternative to the standard hot metal cavity configuration. In addition to its main purpose of ion beam production, the RILIS is used for laser spectroscopy of radioisotopes. In an ongoing experimental campaign the isotope shifts and hyperfine structure of long isotopic chains have been measured by the extremely sensitive in-source laser spectroscopy method. The studies performed in the lead region were focused on nuclear deformation and shape coexistence effects around the closed proton shell Z = 82. The paper describes the functional principles of the RILIS, the current status of the laser system and demonstrated capabilities for the production of different ion beams including the high-resolution studies of short-lived isotopes and other applications of RILIS lasers for ISOLDE experiments.

Precision electron-capture energy in 202Pb and its relevance for neutrino mass determination

Within the framework of an extensive programme devoted to the search for alternative candidates for the neutrino mass determination, the atomic mass difference between 202Pb and 202Tl has been measured with the Penning trap mass spectrometer ISOLTRAP at the ISOLDE facility at CERN. The obtained value $ Q_{{\rm EC}} = 38.8(43)$ keV is three times more precise than the AME2012 value. While it will probably not lead to a replacement of 163Ho in modern experiments on the determination of the electron-neutrino mass, the electron capture in 202Pb would however allow a determination of the electron-neutrino mass on the few-eV level using a cryogenic micro-calorimeter.

New laser polarization line at the ISOLDE facility

Following a growing interest in spin-polarized beams of radioactive ions, a new laser spin-polarization setup has been installed at the ISOLDE facility at CERN. The setup is located at the VITO beamline which aims to bring together several experimental techniques using polarized ions allowing for studies in nuclear physics, fundamental interactions, material and life sciences. Intensive design work, which took place in 2016, allowed the installation of the first stage of the polarization line. With this experimental setup, the ion beam can be neutralized, polarized and implanted into a solid sample inside an electromagnet which also hosts β-detectors, where the degree of nuclear spin polarization can be measured. In autumn 2016 the setup was commissioned using short-lived 26Na and 28Na beams which were polarized in the D2 line from their atomic ground state. The previously observed degrees of β asymmetry were reproduced and thus the beamline is now ready for the first physics experiments with spin-polarized radioactive beams.

Weak interaction physics at ISOLDE

Radioactive nuclei offer unique possibilities to study the structure and symmetries of the weak interaction in nuclear β decay. The large variety of nuclear states available allows selecting the ones that are best suited to study the phenomena of interest with optimal sensitivity, while at the same time minimising the effects of nuclear structure. The ISOLDE facility, offering worldwide the largest variety and intensity of radioactive beams, is one of the best suited laboratories in this respect. Over the last decade or so different aspects of the weak interaction have been studied at ISOLDE, ranging from half-lives, branching ratios and nuclear masses relevant for the determination of the Vud quark-mixing matrix element, over β-asymmetry and correlation measurements searching for possible tensor and/or scalar contributions to the weak interaction, up to a measurement showing the effect of parity violation in the weak interaction in gamma decay. In addition, new projects respectively searching for scalar currents in the β-delayed proton decay of 32Ar, or to determine the Vud quark-mixing matrix element from the β-asymmetry parameter in the mirror decay of 35Ar, have just started.

Penning-trap mass spectrometry and mean-field study of nuclear shape coexistence in the neutron-deficient lead region

We present a study of nuclear shape coexistence in the region of neutron-deficient lead isotopes. The midshell gold isotopes Au180,185,188,190 (Z=79), the two long-lived nuclear states in At197 (Z=85), and the neutron-rich nuclide At219 were produced by the ISOLDE facility at CERN and their masses were determined with the high-precision Penning-trap mass spectrometer ISOLTRAP. The studied gold isotopes address the trend of binding energies in a region of the nuclear chart where the nuclear charge radii show pronounced discontinuities. Significant deviations from the atomic-mass evaluation were found for Au188,190. The new trend of two-neutron separation energies is smoother, although it does reveal the onset of deformation. The origin of this effect is interpreted in connection to the odd-even staggering of binding energies, as well as theoretically by Hartree-Fock-Bogoliubov calculations including quasiparticle blocking. The role of blocking for reproducing the large odd-even staggering of charge radii in the mercury isotopic chain is illustrated.

Development of a processing route for carbon allotrope-based TiC porous nanocomposites

Ti-foils are currently used as a spallation target material to produce radioisotopes for physics research at the ISOLDE facility at CERN. However, radioisotope production rates often decrease over time due to material degradation from high operation temperatures. Due to enhanced release rates, porous nanomaterials are being studied as spallation target materials for isotope production. TiC is a material with a very high melting point making it an interesting material to replace the Ti-foils. However, in its nanometric form it sinters readily at high temperatures. To overcome this, a new processing route was developed where TiC was co-milled with graphite, carbon black or multi-wall carbon nanotubes in order to hinder the sintering of TiC. The obtained nanocomposite particle sizes, density, specific surface area and porosity were characterized and compared using ANOVA. All carbon allotropes mixed with the TiC, were able to successfully stabilize the nanometric TiC, hindering its sintering up to 1500°C for 10h.

Physics with post accelerated beams: nuclear astrophysics

In this article, recent studies so far conducted with post accelerated beams at the ISOLDE facility in the area of nuclear astrophysics are reviewed. Two experiments in particular are highlighted, that each feature novelty and innovation. Three future experiments are also briefly presented. Collectively, these works advance our understanding of big bang nucleosynthesis, quiescent and explosive burning in novae and x-ray bursts, and core-collapse supernovae, both in terms of the underlying explosion mechanism and gamma-ray satellite observable radioisotopes.

Lattice Location of Mg in GaN: A Fresh Look at Doping Limitations.

Radioactive ^{27}Mg (t_{1/2}=9.5 min) was implanted into GaN of different doping types at CERN's ISOLDE facility and its lattice site determined via β^{-} emission channeling. Following implantations between room temperature and 800 °C, the majority of ^{27}Mg occupies the substitutional Ga sites; however, below 350 °C significant fractions were also found on interstitial positions ∼0.6 Å from ideal octahedral sites. The interstitial fraction of Mg was correlated with the GaN doping character, being highest (up to 31%) in samples doped p type with 2×10^{19} cm^{-3} stable Mg during epilayer growth, and lowest in Si-doped n-GaN, thus giving direct evidence for the amphoteric character of Mg. Implanting above 350 °C converts interstitial ^{27}Mg to substitutional Ga sites, which allows estimating the activation energy for migration of interstitial Mg as between 1.3 and 2.0eV.

Precision mass measurements of cesium isotopes—new entries in the ISOLTRAP chronicles

Alkali ion beams are among the most intense produced by the ISOLDE facility. These were the first to be studied by the ISOLTRAP mass spectrometer and ever since, new measurements have been regularly reported. Recently the masses of very neutron-rich and short-lived cesium isotopes were determined at ISOLTRAP. The isotope 148Cs was measured directly for the first time by Penning-trap mass spectrometry. Using the new results, the trend of two-neutron separation energies in the cesium isotopic chain is revealed to be smooth and gradually decreasing, similar to the ones of the barium and xenon isotopic chains. Predictions of selected microscopic models are employed for a discussion of the experimental data in the region.

Application of the Broad Energy Germanium detector: A technique for elucidating β-decay schemes which involve daughter nuclei with very low energy excited states

A technique for elucidating β-decay schemes of isotopes with a large density of states at low excitation energy has been developed, in which a Broad Energy Germanium (BEGe) detector is used in conjunction with coaxial hyper-pure germanium detectors. The power of this technique is demonstrated using the example of 183Hg decay. Mass-separated samples of 183Hg were produced by a deposition of the low-energy radioactive-ion beam delivered by the ISOLDE facility at CERN. The excellent energy resolution of the BEGe detector allowed γ-ray energies to be determined with a precision of a few tens of eV, which was sufficient for the analysis of the Rydberg-Ritz combinations (in conjunction with γ-γ coincidences) in the level scheme. The timestamped structure of the data was used for unambiguous separation of γ rays arising from the decay of 183Hg from those due to the daughter decays.