Novel radionuclides: demand, production and distribution for translational research in Europe.

Background: In the field of medical and scientific research, radionuclides are used to investigate various physiological and pathological processes. PRISMAP - the European medical radionuclide programme was created to bring together production facilities including intense neutron sources, an isotope mass separation facility, high-power accelerators, biomedical research institutes, and hospitals to support medical research. The aim of this article is to introduce readers with the current status of innovative radionuclides in Europe.

Terbium sisters: current development status and upscaling opportunities.

The interest in terbium radionuclides, which can be used in nuclear medicine, has increased tremendously over the last decade. Several research studies have shown the potential of four terbium radionuclides Tb both for cancer diagnosis as well as therapy. The comparison of Tb and Lu showed Tb as the preferred candidate not only for standard radiotherapy, but also for the treatment of minimal residual disease.

The half-life re-measured: consolidating the chronometer for events in the early Solar System.

The half-life of the extinct radiolanthanide , important for both geochronological and astrophysical applications, was re-determined by a combination of mass spectrometry and -decay counting. Earlier studies provided only limited information on all potential factors that could influence the quantification of the half-life of . Thus, special attention was given  here to a complete documentation of all experimental steps to provide information about any possible artifacts in the data analysis.

Preclinical Evaluation of Gastrin-Releasing Peptide Receptor Antagonists Labeled with Tb and Lu: A Comparative Study.

To elucidate potential benefits of the Auger-electron-emitting radionuclide Tb, we compared the preclinical performance of the gastrin-releasing peptide receptor antagonists RM2 (DOTA-Pip-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH) and AMTG (α-Me-Trp-RM2), each labeled with both Lu and Tb. Tb/Lu labeling (90°C, 5 min) and cell-based experiments (PC-3 cells) were performed. In vivo stability (30 min after injection) and biodistribution studies (1-72 h after injection) were performed on PC-3 tumor-bearing CB17-SCID mice.

Synthesis and Preclinical Evaluation of Radiolabeled [Ru]BOLD-100.

The first-in-class ruthenium-based chemotherapeutic agent BOLD-100 (formerly IT-139, NKP-1339, KP1339) is currently the subject of clinical evaluation for the treatment of gastric, pancreatic, colorectal and bile duct cancer. A radiolabeled version of the compound could present a helpful diagnostic tool. Thus, this study investigated the pharmacokinetics of BOLD-100 in more detail to facilitate the stratification of patients for the therapy.

Study of thulium-167 cyclotron production: a potential medically-relevant radionuclide.

Targeted Radionuclide Therapy is used for the treatment of tumors in nuclear medicine, while sparing healthy tissues. Its application to cancer treatment is expanding. In particular, Auger-electron emitters potentially exhibit high efficacy in treating either small metastases or single tumor cells due to their short range in tissue.

Novel radionuclides for use in Nuclear Medicine in Europe: where do we stand and where do we go?

Background: In order to support the ongoing research across Europe to facilitate access to novel radionuclides, the PRISMAP consortium (European medical radionuclides programme) was established to offer the broadest catalog of non-conventional radionuclides for medical and translational research. The aim of this article is to introduce readers with current status of novel radionuclides in Europe.

Main Body: A consortium questionnaire was disseminated through the PRISMAP consortium and user community, professional associations and preclinical/clinical end users in Europe and the current status of clinical end-users in nuclear medicine were identified.

Cross-section measurement of thulium radioisotopes with an 18 MeV medical PET cyclotron for an optimized Er production.

Er is a pure Auger-electron emitter with promising characteristics for therapeutic applications in nuclear medicine. The short penetration path and high Linear Energy Transfer (LET) of the emitted Auger electrons make Er particularly suitable for treating small tumor metastases. Several production methods based on the irradiation with charged particles of Er and Ho targets can be found in the literature.

Tb-DOTATOC Production Using a Fully Automated Disposable Cassette System: A First Step Toward the Introduction of Tb into the Clinic.

Tb is an interesting radionuclide for application in the treatment of neuroendocrine neoplasms' small metastases and single cancer cells because of its conversion and Auger-electron emission. Tb has coordination chemistry similar to that of Lu; therefore, like Lu, it can stably radiolabel DOTATOC, one of the leading peptides used for the treatment of neuroendocrine neoplasms. However, Tb is a recently developed radionuclide that has not yet been specified for clinical use.

Activity Measurement of Sc and Calibration of Activity Measurement Instruments on Production Sites and Clinics.

Sc is a promising radionuclide for positron emission tomography (PET) in nuclear medicine. As a part of the implementation of a production site for Sc, precise knowledge of the activity of the product is necessary. At the Paul Scherrer Institute (PSI) and the University of Bern (UniBE), Sc is produced by enriched CaO-target irradiation with a cyclotron.

Determination of the half-life of gadolinium-148.

The half-life of the alpha-emitter Gd was measured using the "direct method", in which the number of atoms is directly determined and their activity is then measured. Pure Gd samples containing megabecquerels of Gd were obtained by reprocessing proton-irradiated tantalum material. Multicollector-inductively coupled plasma mass spectrometry was performed to determine the amount of Gd atoms retrieved.

[Ac]Ac-SibuDAB for Targeted Alpha Therapy of Prostate Cancer: Preclinical Evaluation and Comparison with [Ac]Ac-PSMA-617.

In the present study, SibuDAB, an albumin-binding PSMA ligand, was investigated in combination with actinium-225 and the data were compared with those of [Ac]Ac-PSMA-617. In vitro, [Ac]Ac-SibuDAB and [Ac]Ac-PSMA-617 showed similar tumor cell uptake and PSMA-binding affinities as their Lu-labeled counterparts. The in vitro binding to serum albumin in mouse and human blood plasma, respectively, was 2.

Half-life measurement of Sc and Sc.

The half-lives of Sc and Sc were measured by following their decay rate using several measurement systems: two ionization chambers and three γ-spectrometry detectors with digital and/or analogue electronics. For Sc, the result was the combination of seven half-life values giving a result of 4.042(7) h, which agrees with the last reported value of 4.

Chelation of Theranostic Copper Radioisotopes with S-Rich Macrocycles: From Radiolabelling of Copper-64 to In Vivo Investigation.

Copper radioisotopes are generally employed for cancer imaging and therapy when firmly coordinated via a chelating agent coupled to a tumor-seeking vector. However, the biologically triggered Cu-Cu redox switching may constrain the in vivo integrity of the resulting complex, leading to demetallation processes. This unsought pathway is expected to be hindered by chelators bearing N, O, and S donors which appropriately complements the borderline-hard and soft nature of Cu and Cu.

High precision half-life measurement of the extinct radio-lanthanide Dysprosium-154.

Sixty years after the discovery of Dy, the half-life of this pure alpha-emitter was re-measured. Dy was radiochemically separated from proton-irradiated tantalum samples. Sector field- and multicollector-inductively coupled plasma mass spectrometry were used to determine the amount of Dy retrieved.

Cross section measurement of terbium radioisotopes for an optimized Tb production with an 18 MeV medical PET cyclotron.

Tb [t = 5.32 d, E = 87 keV (32%); 105 keV (25%) (IAEA, 2021)] is a novel promising radionuclide for theranostic applications in nuclear medicine. Its physical properties make it suitable for single photon emission computed tomography (SPECT) imaging, while its chemistry allows it to be used as a diagnostic partner for therapeutic radiolanthanides or pseudo-radiolanthanides, such as Lu and Y.

Precise activity measurements of medical radionuclides using an ionization chamber: a case study with Terbium-161.

Background: Tb draws an increasing interest in nuclear medicine for therapeutic applications. More than 99% of the emitted gamma and X-rays of Tb have an energy below 100 keV. Consequently, precise activity measurement of Tb becomes inaccurate with radionuclide dose calibrators when using inappropriate containers or calibration factors to account for the attenuation of this low energy radiation.

Efficient Production of High Specific Activity Thulium-167 at Paul Scherrer Institute and CERN-MEDICIS.

Thulium-167 is a promising radionuclide for nuclear medicine applications with potential use for both diagnosis and therapy ("theragnostics") in disseminated tumor cells and small metastases, due to suitable gamma-line as well as conversion/Auger electron energies. However, adequate delivery methods are yet to be developed and accompanying radiobiological effects to be investigated, demanding the availability of Tm in appropriate activities and quality. We report herein on the production of radionuclidically pure Tm from proton-irradiated natural erbium oxide targets at a cyclotron and subsequent ion beam mass separation at the CERN-MEDICIS facility, with a particular focus on the process efficiency.

Ytterbium-175 half-life determination.

Yb is a radionuclide that can be generated by neutron capture on Yb and whose decay properties make it useful for developing therapeutic radiopharmaceuticals. As it happens with many of the emerging radionuclides for medical uses in recent years, its nuclear data were determined decades ago and are not thoroughly documented nor accurate enough for metrological purposes. The last documented reference for the Yb half-life value is 4.

CERN-MEDICIS: A Review Since Commissioning in 2017.

The CERN-MEDICIS (MEDical Isotopes Collected from ISolde) facility has delivered its first radioactive ion beam at CERN (Switzerland) in December 2017 to support the research and development in nuclear medicine using non-conventional radionuclides. Since then, fourteen institutes, including CERN, have joined the collaboration to drive the scientific program of this unique installation and evaluate the needs of the community to improve the research in imaging, diagnostics, radiation therapy and personalized medicine. The facility has been built as an extension of the ISOLDE (Isotope Separator On Line DEvice) facility at CERN.

Radiochemical Determination of Long-Lived Radionuclides in Proton-Irradiated Heavy Metal Targets: Part II Tungsten.

In this study, proton-irradiated tungsten targets, up to 2.6 GeV, were investigated for the purpose of the experimental cross-section measurements. Radiochemical separation methods were applied to isolate the residual long-lived alpha-emitters Gd, Dy, and Sm and the beta-emitters I and Cl from proton-irradiated tungsten targets.

Determination of the gamma and X-ray emission intensities of erbium-169.

The gamma and X-ray emission intensities of Er were determined using radionuclidically pure Er. The activity of the Er source was standardized by the triple-to-double-coincidence ratio technique. Three independent measurements were performed to measure the emission intensities using calibrated high-purity germanium spectrometers.

Determination of the gamma and X-ray emission intensities of terbium-161.

In this study, the gamma and X-ray emission intensities of Tb were determined using a high-purity germanium spectrometer. The samples used were previously standardised by coincidence counting and Triple to Double Coincidence Ratio (TDCR) methods. A total of 28 gamma-rays and 4 X-rays were measured and compared with previous measurements performed more than 30 years ago.

Production of Mass-Separated Erbium-169 Towards the First Preclinical Investigations.

The β-particle-emitting erbium-169 is a potential radionuclide toward therapy of metastasized cancer diseases. It can be produced in nuclear research reactors, irradiating isotopically-enriched ErO. This path, however, is not suitable for receptor-targeted radionuclide therapy, where high specific molar activities are required.