Hiromitsu Haba

Targeted alpha therapy is generally evaluated by absorbed dose and direct tumor-cell killing, but whether alpha-particle–injured tumor cells can induce systemic antitumor immunity remains poorly defined. We investigated the immunogenic consequences of astatine-211 (²¹¹At) injury in a prophylactic melanoma vaccination–challenge model. B16F10 cells were exposed ex vivo to ²¹¹At, etoposide, or ultraviolet irradiation under conditions that reduced viable-cell counts at 24 hours to approximately 40% of untreated controls. Injured cells were administered subcutaneously to syngeneic C57BL/6J mice before intravenous challenge with viable B16F10 cells. Vaccination with cells exposed to 1 MBq/mL ²¹¹At suppressed pulmonary metastasis, reduced regulatory T-cell proportions, and elicited tumor-reactive interferon-γ responses and antibodies. Transcriptomic profiling revealed enrichment of type I interferon, inflammatory, and chemokine-related signatures, together with suppression of cell-cycle, translation, and metabolic programs. At the cellular level, ²¹¹At injury was accompanied by γH2AX accumulation, G2/M arrest, increased reactive oxygen species and cytosolic double-stranded DNA, and senescence-like changes. These features arose without consistent increases in classical damage-associated molecular patterns or prominent induction of senescence-associated secretory phenotype factors at 1 MBq/mL. In vivo pharmacologic inhibition of stimulator of interferon genes (STING) signaling attenuated the antimetastatic effect of vaccination. Together, these findings demonstrate that ²¹¹At injury can generate an immunostimulatory tumor-cell state characterized by DNA damage and altered inflammatory signaling. STING contributes to the resulting immune protection, highlighting immunogenic tumor-cell conversion as a consideration in the design of targeted alpha therapies.

This work reports on the measurements performed during the commissioning of the GARIS-III separator in RIKEN with the study of the ⁴⁰ Ar + ²⁰⁸ Pb → ²⁴⁸ Fm ^* reaction. The excitation functions of the 2n, 3n, and 4n exit channels were measured with maximum cross sections of 27.5 ± 6.4, 37.4 ± 6.2, and 2.45 ± 0.52 nb, respectively. The obtained results were also compared to previous measurements from GSI and GARIS-II, as well as to theoretical statistical models. The measurements were also used to fully characterize the GARIS-III separator regarding its transmission, implantation profile and detection efficiency of the focal plane detector system.

The chemical properties of transfermium elements with atomic numbers >100 are largely unknown. Element 102, nobelium, is an actinide and forms stable +2 valent cations in aqueous solutions, unlike other heavy actinide. In previous experiments, No ²⁺ exhibits similar behavior to alkaline earth metal ions, particularly Ca ²⁺ and Sr ²⁺ , suggesting hard-acid character. In this study, the soft metal ion behavior of No ²⁺ was demonstrated through complex with crown ethers. In the solid–liquid extraction of ²⁵⁵ No using di- ^t Bu-dicyclohexano-18-crown-6 in HNO ₃ , No ²⁺ was extracted as much as Sr ²⁺ . Density functional theory calculations confirmed higher stability of the No ²⁺ –DtBuCH18C6 complex, with covalent bonding involving the 6 d orbitals. Theoretical studies also revealed strong relativistic effects on the atomic orbitals of No ²⁺ , rendering No ²⁺ a soft ion similar to Pb ²⁺ .

We demonstrated the production of high-intensity and low-energy neutral francium (Fr221) by developing an atomic source based on actinium (Ac225) covered with an yttrium (Y) layer. Low-energy Fr+221 ions and neutral Fr221 atoms were produced and measured. We investigated the flux and number of Fr221 atoms from the experimental results under different experimental conditions. The proposed atomic source is promising for Fr trapping experiments and Fr electric dipole moment measurements.

Activation cross sections of alpha-particle-induced reactions on 197Au were measured using the stacked-foil activation technique and high-resolution gamma-ray spectrometry. Production cross sections of 200, 199, 198g, 198m, 197g, 196mTl, 197g, 197mHg, and 196g, 195g, 194gAu and physical thick target yields of 200, 199, 198gTl, 197g, 197mHg, and 196g, 195g, 194gAu were determined for alpha-particle energies up to 50 MeV. The measured excitation functions were compared with previously reported experimental data and theoretical predictions from the TENDL-2025 library. The experimentally determined thick target yields showed good agreement with those calculated from the measured cross sections, confirming the high reliability of our experimental data. The measured cross sections and yield data provide valuable information for the production of thallium radioisotopes and for improving nuclear reaction model calculations.

Background/Objectives: Peritoneal dissemination of malignancies leads to poor prognoses, and no effective treatment currently exists. The difficulty of treating such malignancies is likely because systemically administered drugs cannot easily target malignant cells in the abdominal cavity. High intraperitoneal drug retention, non-toxicity towards normal tissues, and successful targeting of malignant cells are important for an effective therapy. The aim of this study was to evaluate an intraperitoneally administered astatine-labeled, integrin-targeted nanodrug, mPEG(Mn:350)-S-AuNP[²¹¹At]-c[RGDfK(C)] ([²¹¹At]AuNP@PEG/RGD), with respect to its kinetics, therapeutic efficacy, and safety. Methods: C6 rat glioma cells (10⁷), and BxPC3 (10⁷) and PANC-1 (10⁷) human pancreatic cancer cells were seeded intraperitoneally into nude mice, and [²¹¹At]AuNP@PEG/RGD (0.979 ± 0.194 MBq for C6 models (n = 3), 1.139 ± 0.035 MBq for BxPC3 models (n = 10), and 1.308 ± 0.039 MBq for PANC-1 models (n = 10) per mouse) or saline were intraperitoneally administered 4–7 days later. Cytotoxicity against malignant cells, pharmacokinetics after administration, therapeutic efficacy, and safety in abdominal organs were evaluated. Results: Intraperitoneally administered [²¹¹At]AuNP@PEG/RGD accumulated exclusively in the peritoneal cavity for a long period of time and showed minimal systemic diffusion through the blood. In the C6 model, the intraperitoneal tumor mass was significantly lower in the treated group compared with that of the controls (p = 0.05). For the BxPC3 (median survival time: control/treated = 41/65 days, p < 0.001) and PANC-1 (median survival time: control/treated = 19/35 days, p < 0.001) peritoneal dissemination models, survival analysis revealed that [²¹¹At]AuNP@PEG/RGD significantly prolonged overall survival. Although transient weight loss, leukopenia, and thrombocytopenia were observed at one week post-administration, a short recovery trend was evident thereafter. One month after administration, no abnormalities were found in hematological tests or histological analyses of intra-abdominal organs. Conclusions: The intraperitoneal administration of astatine-labeled integrin-targeted [²¹¹At]AuNP@PEG/RGD nanoparticles showed promising findings in terms of safety and efficacy for treating peritoneally disseminated malignant tumors.

We developed a 400-m polarization-maintaining optical fiber delivery system for magneto-optical trapping of radioactive Fr atoms at RIKEN in Japan. The optical system is useful for the precise studies of the electron’s electric dipole moment and the parity nonconservation effect in atomic systems. The power saturation effect due to the stimulated Brillouin scattering in the fiber was investigated. Polarization fluctuation was optimized to be below 5 × 10−3. The absolute frequency of the stabilized laser was measured with an absolute accuracy of 1.5 MHz using a high-performance commercial wavelength meter. In addition, the absolute frequencies of hyperfine transitions of iodine molecules (127I2) near 718 nm were determined. We demonstrated laser cooling of Rb with 440-m optical fiber delivery.