Development of LAT1-Selective Nuclear Medicine Therapeutics Using Astatine-211.

We investigated nuclear medicine therapeutics targeting the L-type amino acid transporter 1 (LAT1). We previously reported that a nuclear medicine therapeutic drug using astatine 211 (At), an alpha-emitting nuclide that can be produced in an accelerator and targets LAT1 as a molecular target, is effective. The seed compound was 3-[At] Astato-α-methyl-L-tyrosine (At-AAMT-OH-L).

Comparison Length of Linker in Compound for Nuclear Medicine Targeting Fibroblast Activation Protein as Molecular Target.

Novel nuclear medicine therapeutics are being developed by labeling medium-molecular-weight compounds with short-lived alpha-emitting radionuclides. Fibroblast activation protein α (FAPα) is recognized as a highly useful molecular target, and its inhibitor, FAPI, is a compound capable of , both therapeutic and diagnostic, for cancer treatment. In this study, we compared the functions of two compounds that target FAPα: At-FAPI1 and At-FAPI2.

Activation cross sections of alpha-particle-induced reactions on natural rhenium up to 50 MeV.

Activation cross sections of alpha-particle-induced reactions on natural rhenium were measured. The stacked-foil activation technique and high-resolution gamma-ray spectrometry were used to derive the cross sections. The production cross sections of Ir, Os, and Re were determined up to 50 MeV.

Precise Spectroscopy of the 3n and 3p Systems via the ^{3}H(t, ^{3}He)3n and ^{3}He(^{3}He, t)3p Reactions at Intermediate Energies.

To search for low-energy resonant structures in isospin T=3/2 three-body systems, we have performed the experiments ^{3}H(t,^{3}He)3n and ^{3}He(^{3}He,t)3p at intermediate energies. For the 3n experiment, we have newly developed a thick Ti-^{3}H target that has the largest tritium thickness among targets of this type ever made. The 3n experiment for the first time covered the momentum-transfer region as low as 15  MeV/c, which provides ideal conditions for producing fragile systems.

Controlling Th isomeric state population in a VUV transparent crystal.

The radioisotope thorium-229 (Th) is renowned for its extraordinarily low-energy, long-lived nuclear first-excited state. This isomeric state can be excited by vacuum ultraviolet (VUV) lasers and Th has been proposed as a reference transition for ultra-precise nuclear clocks. To assess the feasibility and performance of the nuclear clock concept, time-controlled excitation and depopulation of the Th isomer are imperative.

Preclinical Evaluation of Biodistribution and Toxicity of [At]PSMA-5 in Mice and Primates for the Targeted Alpha Therapy against Prostate Cancer.

Astatine (At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the At-labeled prostate-specific membrane antigen (PSMA) compound ([At]PSMA-5) exhibited excellent tumor growth suppression in a xenograft model.

Laser spectroscopy of triply charged Th isomer for a nuclear clock.

Thorium-229 (Th) possesses an optical nuclear transition between the ground state (Th) and low-lying isomer (Th). A nuclear clock based on this nuclear-transition frequency is expected to surpass existing atomic clocks owing to its insusceptibility to surrounding fields. In contrast to other charge states, triply charged Th (Th) is the most suitable for highly accurate nuclear clocks because it has closed electronic transitions that enable laser cooling, laser-induced fluorescence detection and state preparation of ions.

Production of [At]NaAt solution under GMP compliance for investigator-initiated clinical trial.

Background: The alpha emitter astatine-211 (At) is garnering attention as a novel targeted alpha therapy for patients with refractory thyroid cancer resistant to conventional therapy using beta emitter radioiodine (I). Herein, we aimed to establish a robust method for the manufacturing and quality control of [At]NaAt solution for intravenous administration under the good manufacturing practice guidelines for investigational products to conduct an investigator-initiated clinical trial.

Results: At was separated and purified via dry distillation using irradiated Bi plates containing At obtained by the nuclear reaction of Bi(He, 2n)At.

Metallic radionuclide-labeled tetrameric 2,6-diisopropylphenyl azides for cancer treatment.

This study proposes a new method for radionuclide therapy that involves the use of oligomeric 2,6-diisopropylphenyl azides and a chelator to form stable complexes with metallic radionuclides. The technique works by taking advantage of the endogenous acrolein produced by cancer cells. The azides react with the acrolein to give a diazo derivative that immediately attaches to the nearest organelle, effectively anchoring the radionuclide within the tumor.

Alpha-particle-induced reactions on natural silver in the 10-50 MeV energy range: Production of In, In and Cd.

Production cross sections of medical radionuclides In, In and Cd were investigated in the α-particle-induced reactions on natural silver up to 50 MeV. The stacked-foil activation technique and γ-ray spectrometry were used to determine the cross sections. The excitation functions of byproducts Ag, Cd and In were also determined.

Comparison of Nuclear Medicine Therapeutics Targeting PSMA among Alpha-Emitting Nuclides.

Currently, targeted alpha therapy (TAT) is a new therapy involving the administration of a therapeutic drug that combines a substance of α-emitting nuclides that kill cancer cells and a drug that selectively accumulates in cancer cells. It is known to be effective against cancers that are difficult to treat with existing methods, such as cancer cells that are widely spread throughout the whole body, and there are high expectations for its early clinical implementation. The nuclides for TAT, including Tb, At, Bi, Pb (for Bi), Ra, Ac, Th, and U, are known.

Immuno-PET and Targeted α-Therapy Using Anti-Glypican-1 Antibody Labeled with Zr or At: A Theranostic Approach for Pancreatic Ductal Adenocarcinoma.

Glypican-1 (GPC1) is overexpressed in several solid cancers and is associated with tumor progression, whereas its expression is low in normal tissues. This study aimed to evaluate the potential of an anti-GPC1 monoclonal antibody (GPC1 mAb) labeled with Zr or At as a theranostic target in pancreatic ductal adenocarcinoma. GPC1 mAb clone 01a033 was labeled with Zr or At with a deferoxamine or decaborane linker, respectively.

Therapeutic efficacy of At-radiolabeled 2,6-diisopropylphenyl azide in mouse models of human lung cancer.

Targeted α-particle therapy (TAT) is an attractive alternative to conventional therapy for cancer treatment. Among the available radionuclides considered for TAT, astatine-211 (At) attached to a cancer-targeting molecule appears very promising. Previously, we demonstrated that aryl azide derivatives could react selectively with the endogenous acrolein generated by cancer cells to give a diazo compound, which subsequently forms a covalent bond with the organelle of cancer cells .

Exploring a Nuclear-Selective Radioisotope Delivery System for Efficient Targeted Alpha Therapy.

Targeted alpha therapy (TAT) has garnered significant interest as an innovative cancer therapy. Owing to their high energy and short range, achieving selective α-particle accumulation in target tumor cells is crucial for obtaining high potency without adverse effects. To meet this demand, we fabricated an innovative radiolabeled antibody, specifically designed to selectively deliver At (α-particle emitter) to the nuclei of cancer cells.

Evaluation of Astatine-211-Labeled Fibroblast Activation Protein Inhibitor (FAPI): Comparison of Different Linkers with Polyethylene Glycol and Piperazine.

Fibroblast activation proteins (FAP) are overexpressed in the tumor stroma and have received attention as target molecules for radionuclide therapy. The FAP inhibitor (FAPI) is used as a probe to deliver nuclides to cancer tissues. In this study, we designed and synthesized four novel At-FAPI(s) possessing polyethylene glycol (PEG) linkers between the FAP-targeting and At-attaching moieties.

Tumor Targeting of At-Labeled Antibody under Sodium Ascorbate Protection against Radiolysis.

Astatine-211 (At) is an alpha emitter applicable to radioimmunotherapy (RIT), a cancer treatment that utilizes radioactive antibodies to target tumors. In the preparation of At-labeled monoclonal antibodies (At-mAbs), the possibility of radionuclide-induced antibody denaturation (radiolysis) is of concern. Our previous study showed that this At-induced radiochemical reaction disrupts the cellular binding activity of an astatinated mAb, resulting in attenuation of antitumor effects, whereas sodium ascorbate (SA), a free radical scavenger, prevents antibody denaturation, contributing to the maintenance of binding and antitumor activity.

Astatine-211-Labeled Gold Nanoparticles for Targeted Alpha-Particle Therapy via Intravenous Injection.

Alpha-particle radiotherapy has gained considerable attention owing to its potent anti-cancer effect. At, with a relatively short half-life of 7.2 h, emits an alpha particle within a few cell diameters with high kinetic energy, which damages cancer cells with high biological effectiveness.

Effect to Therapy of Sodium-Iodine Symporter Expression by Alpha-Ray Therapeutic Agent via Sodium/Iodine Symporter.

This study confirmed the effect of sodium/iodine symporter (NIS) expression on existing drugs by in vitro and in vivo tests using cultured cell lines. The tumor growth inhibitory effect of sodium astatide ([At]NaAt) was evaluated by in vitro and in vivo tests using human thyroid cancer cells (K1, K1/NIS and K1/NIS-DOX). NIS expression in cancer cells was controlled using the Tet-On system.

Activation cross sections of proton-induced reactions on natural platinum up to 30 MeV.

Activation cross sections of proton-induced reactions on natural platinum were measured. The stacked-foil activation technique and high-resolution gamma-ray spectrometry were used. The production cross sections of Au, Pt, and Ir were determined up to 30 MeV.

Facility upgrade for superheavy-element research at RIKEN.

The RIKEN Nishina Center (RNC) executed an accelerator upgrade project for the heavy-ion linac (called RILAC). A superconducting RIKEN linear accelerator (SRILAC) and a new superconducting electron-cyclotron-resonance ion source (SC-ECRIS) to boost the final energy and intensity were constructed, aimed at synthesizing a new superheavy element, 119, through a hot fusion reaction. The project included the construction of a gas-filled recoil ion separator (GARIS-III) suitable for detecting the residues of the hot-fusion reaction.

Targeted α-therapy using astatine (At)-labeled PSMA1, 5, and 6: a preclinical evaluation as a novel compound.

Purpose: Targeted α-therapy (TAT) for prostate-specific membrane antigen (PSMA) is a promising treatment for metastatic castration-resistant prostate cancer (CRPC). Astatine is an α-emitter (half-life=7.2 h) that can be produced by a 30-MeV cyclotron.

On the adsorption and reactivity of element 114, flerovium.

Flerovium (Fl, element 114) is the heaviest element chemically studied so far. To date, its interaction with gold was investigated in two gas-solid chromatography experiments, which reported two different types of interaction, however, each based on the level of a few registered atoms only. Whereas noble-gas-like properties were suggested from the first experiment, the second one pointed at a volatile-metal-like character.

Comparison of the Therapeutic Effects of [At]NaAt and [I]NaI in an NIS-Expressing Thyroid Cancer Mouse Model.

Astatine (At) is an alpha-emitter with a better treatment efficacy against differentiated thyroid cancer compared with iodine (I), a conventional beta-emitter. However, its therapeutic comparison has not been fully evaluated. In this study, we compared the therapeutic effect between [At]NaAt and [I]NaI.

Production cross sections of samarium-153 and -145 via alpha-particle-induced reactions on natural neodymium.

Production cross sections of Sm via alpha-particle-induced reactions on Nd were measured up to 23 MeV. The stacked-foil activation technique and high-resolution gamma-ray spectrometry were adopted for the measurement. The obtained cross sections were compared with the literature data and the TENDL-2019 and TENDL-2021 values.