Terbium-149 (T
= 4.1 h, E
= 3.98 MeV (16.7%), 28 µm range in tissue) is a radionuclide with potential for targeted alpha therapy. Due to the negligible emission of α-emitting daughter nuclides, ...toxicity to healthy tissue may be reduced in comparison with other α-particle emitters. In this study, terbium-149 was produced via 1.4 GeV proton irradiation of a tantalum target at the CERN-ISOLDE facility. The spallation products were mass separated and implanted on zinc-coated foils and, later, radiochemically processed. Terbium-149 was separated from the co-produced isobaric radioisotopes and the zinc coating from the implantation foil, using cation-exchange and extraction chromatographic techniques, respectively. At the end of separation, up to 260 MBq terbium-149 were obtained with > 99% radionuclidic purity. Radiolabeling experiments were performed with DOTATATE, achieving 50 MBq/nmol apparent molar activity with radiochemical purity > 99%. The chemical purity was determined by inductively coupled plasma-mass spectrometry measurements, which showed lead, copper, iron and zinc only at ppb level. The radiolabeling of the somatostatin analogue DOTATATE with
TbTbCl
and the subsequent in vivo PET/CT scans conducted in xenografted mice, showing good tumor uptake, further demonstrated product quality and its ability to be used in a preclinical setting.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
The in vivo-generator radionuclides
140
Nd (t
1/2
= 3.4 d) and
134
Ce (t
1/2
= 3.2 d) were used to trace a urokinase-type plasminogen activator (uPA)-targeting mouse monoclonal antibody, ...ATN-291, in U87 MG xenograft tumor-bearing mice. ATN-291 is known to internalize on the uPA/uPA-receptor pair, making it an appropriate targeting vector for investigating the fate of in vivo generator daughters on internalizing probes.
Ante-mortem
and
post-mortem
PET imaging at 120 h post-injection gave no indication of redistribution of the positron emitting daughter nuclides
134
La and
140
Pr from tumor tissue (
p
> 0.5). The lack of redistribution indicates that the parent radionuclides
134
Ce and
140
Nd could be considered as long-lived PET-diagnostic matches to therapeutic radionuclides like
177
Lu,
161
Tb and
225
Ac when internalizing bioconjugates are employed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The use of radioactive molecules for fundamental physics research is a developing interdisciplinary field limited dominantly by their scarce availability. In this work, radioactive molecular ion ...beams containing actinide nuclei extracted from uranium carbide targets are produced via the Isotope Separation On-Line technique at the CERN-ISOLDE facility. Two methods of molecular beam production are studied: extraction of molecular ion beams from the ion source, and formation of molecular ions from the mass-separated ion beam in a gas-filled radio-frequency quadrupole ion trap. Ion currents of U+, UO1−3+, UC1−3+, UF1−4+, UF1,2O1,2+ are reported. Metastable tantalum and uranium fluoride molecular ions are identified. Formation of UO1−3+, U(OH)1−3+, UC1−3+, UF1,2O1,2+ from mass-separated beams of U+, UF1,2+ with residual gas is observed in the ion trap. The effect of trapping time on molecular formation is presented.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BOLD-100 (formerly IT-139, KP1339), a well-established chemotherapeutic agent, is currently being investigated in clinical trials for the treatment of gastric, pancreatic, colorectal, and bile duct ...cancer. Despite numerous studies, the exact mode of action is still the subject of discussions. Radiolabeled BOLD-100 could be a powerful tool to clarify pharmacokinetic pathways of the compound and to predict therapy responses in patients using nuclear molecular imaging prior to the therapy. In this study, the radiosyntheses of carrier-added (c.a.)
97/103
RuBOLD-100 were performed with the two ruthenium isotopes ruthenium-103 (
103
Ru; β
−
, γ) and ruthenium-97 (
97
Ru; EC, γ), of which in particular the latter isotope is suitable for imaging by single-photon emission computed tomography (SPECT). To identify the best tumor-to-background ratio for diagnostic imaging, biodistribution studies were performed with two different injected doses of c.a.
103
RuBOLD-100 (3 and 30 mg kg
−1
) in Balb/c mice bearing CT26 allografts over a time period of 72 h. Additionally,
ex vivo
autoradiography of the tumors (24 h p.i.) was conducted. Our results indicate that the higher injected dose (30 mg kg
−1
) leads to more unspecific accumulation of the compound in non-targeted tissue, which is likely due to an overload of the albumin transport system. It was also shown that lower amounts of injected c.a.
103
RuBOLD-100 resulted in a relatively higher tumor uptake and, therefore, a better tumor-to-background ratio, which are encouraging results for future imaging studies using c.a.
97
RuBOLD-100.
Radiolabeling of the chemotherapeutic agent BOLD-100 with ruthenium-103 enables animal experiments with lower amounts of injected drug. This leads to a relatively higher tumor uptake and promising tumor-to-background ratio for future imaging studies.
Background
It has been proposed, and preclinically demonstrated, that
161
Tb is a better alternative to
177
Lu for the treatment of small prostate cancer lesions due to its high emission of ...low-energy electrons.
161
Tb also emits photons suitable for single-photon emission computed tomography (SPECT) imaging. This study aims to establish a SPECT protocol for
161
Tb imaging in the clinic.
Materials and methods
Optimal settings using various γ-camera collimators and energy windows were explored by imaging a Jaszczak phantom, including hollow-sphere inserts, filled with
161
Tb. The collimators examined were extended low-energy general purpose (ELEGP), medium-energy general purpose (MEGP), and low-energy high resolution (LEHR), respectively. In addition, three ordered subset expectation maximization (OSEM) algorithms were investigated: attenuation-corrected OSEM (A-OSEM); attenuation and dual- or triple-energy window scatter-corrected OSEM (AS-OSEM); and attenuation, scatter, and collimator-detector response-corrected OSEM (ASC-OSEM), where the latter utilized Monte Carlo-based reconstruction. Uniformity corrections, using intrinsic and extrinsic correction maps, were also investigated. Image quality was assessed by estimated recovery coefficients (RC), noise, and signal-to-noise ratio (SNR). Sensitivity was determined using a circular flat phantom.
Results
The best RC and SNR were obtained at an energy window between 67.1 and 82.1 keV. Ring artifacts, caused by non-uniformity, were removed with extrinsic uniformity correction for the energy window between 67.1 and 82.1 keV, but not with intrinsic correction. Analyzing the lower energy window between 48.9 and 62.9 keV, the ring artifacts remained after uniformity corrections. The recovery was similar for the different collimators when using a specific OSEM reconstruction. Recovery and SNR were highest for ASC-OSEM, followed by AS-OSEM and A-OSEM. When using the optimized parameter setting, the resolution of
161
Tb was higher than for
177
Lu (8.4 ± 0.7 vs. 10.4 ± 0.6 mm, respectively). The sensitivities for
161
Tb and
177
Lu were 7.41 and 8.46 cps/MBq, respectively.
Conclusion
SPECT with high resolution is feasible with
161
Tb; however, extrinsic uniformity correction is recommended to avoid ring artifacts. The LEHR collimator was the best choice of the three tested to obtain a high-resolution image. Due to the complex emission spectrum of low-energy photons, window-based scatter correction had a minor impact on the image quality compared to using attenuation correction only. On the other hand, performing attenuation, scatter, and collimator-detector correction clearly improved image quality. Based on these data, SPECT-based dosimetry for
161
Tb-labeled radiopharmaceuticals is feasible.
Terbium-152 is one of four terbium radioisotopes that together form a potential theranostic toolbox for the personalised treatment of tumours. As 152 Tb day by positron emission it can be utilised ...for diagnostics by positron emission tomography. For use in radiopharmaceuticals and for activity measurements by an activity calibrator a high radionuclide purity of the material and an accurate and precise knowledge of the half-life is required. Mass-separation and radiochemical purification provide a production route of high purity 152Tb. In the current work, two mass-separated samples from the CERN-ISOLDE facility have been assayed at the National Physical Laboratory to investigate the radionuclide purity. These samples have been used to perform four measurements of the half-life by three independent techniques: high-purity germanium gamma-ray spectrometry, ionisation chamber measurements and liquid scintillation counting. From the four measurement campaigns a half-life of 17.8784(95) h has been determined. The reported half-life shows a significant difference to the currently evaluated half-life (ζ-score = 3.77), with a relative difference of 2.2 % and an order of magnitude improvement in the precision. This work also shows that under controlled conditions the combination of mass-separation and radiochemical separation can provide high-purity 152Tb.
•First half-life measurement of 152Tb since 1970.•Precise half-life of 152Tb determined by three independent techniques from mass-separated samples.•Presented half-life value shows a relative difference of 2.2% from current evaluated value.•Order of magnitude improvement in the precision to the current evaluated value.•Radionuclide contaminants from two mass-separated samples assessed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Isomers close to doubly magic _{28}^{78}Ni_{50} provide essential information on the shell evolution and shape coexistence near the Z=28 and N=50 double shell closure. We report the excitation energy ...measurement of the 1/2^{+} isomer in _{30}^{79}Zn_{49} through independent high-precision mass measurements with the JYFLTRAP double Penning trap and with the ISOLTRAP multi-reflection time-of-flight mass spectrometer. We unambiguously place the 1/2^{+} isomer at 942(10) keV, slightly below the 5/2^{+} state at 983(3) keV. With the use of state-of-the-art shell-model diagonalizations, complemented with discrete nonorthogonal shell-model calculations which are used here for the first time to interpret shape coexistence, we find low-lying deformed intruder states, similar to other N=49 isotones. The 1/2^{+} isomer is interpreted as the bandhead of a low-lying deformed structure akin to a predicted low-lying deformed band in ^{80}Zn, and points to shape coexistence in ^{79,80}Zn similar to the one observed in ^{78}Ni. The results make a strong case for confirming the claim of shape coexistence in this key region of the nuclear chart.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
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