Francium (Fr), which is the alkali atom in the 7th period, can be obtained as ultracold atoms with laser cooling and trapping techniques, and could be employed for the experiments on searches for the ...permanent electric dipole moment (EDM) of an electron. In order to improve the sensitivity of the electron EDM search, development of a high-intensity source of Fr atoms is essential. We demonstrated a production of a high intensity
210
Fr ion beam with a rate of
5
×
10
6
ions/s by a fusion reaction with bombardment of an accelerated
18
O beam onto a fixed gold target in RIKEN. The Fr products inside the gold target were extracted from the gold surface as an ion beam focused with an electrostatic field. We also discussed the method to produce
221
Fr by
α
-decay of
225
Ac. A neutron-rich
221
Fr isotope can be obtained as a daughter nucleus of this decay.
Astatine-211 (211At) is an alpha emitter applicable to radioimmunotherapy (RIT), a cancer treatment that utilizes radioactive antibodies to target tumors. In the preparation of 211At-labeled ...monoclonal antibodies (211At-mAbs), the possibility of radionuclide-induced antibody denaturation (radiolysis) is of concern. Our previous study showed that this 211At-induced radiochemical reaction disrupts the cellular binding activity of an astatinated mAb, resulting in attenuation of in vivo antitumor effects, whereas sodium ascorbate (SA), a free radical scavenger, prevents antibody denaturation, contributing to the maintenance of binding and antitumor activity. However, the influence of antibody denaturation on the pharmacokinetics of 211At-mAbs relating to tumor accumulation, blood circulation time, and distribution to normal organs remains unclear. In this study, we use a radioactive anti-human epidermal growth factor receptor 2 (anti-HER2) mAb to demonstrate that an 211At-induced radiochemical reaction disrupts active targeting via an antigen–antibody interaction, whereas SA helps to maintain targeting. In contrast, there was no difference in blood circulation time as well as distribution to normal organs between the stabilized and denatured immunoconjugates, indicating that antibody denaturation may not affect tumor accumulation via passive targeting based on the enhanced permeability and retention effect. In a high-HER2-expressing xenograft model treated with 1 MBq of 211At-anti-HER2 mAbs, SA-dependent maintenance of active targeting contributed to a significantly better response. In treatment with 0.5 or 0.2 MBq, the stabilized radioactive mAb significantly reduced tumor growth compared to the denatured immunoconjugate. Additionally, through a comparison between a stabilized 211At-anti-HER2 mAb and radioactive nontargeted control mAb, we demonstrate that active targeting significantly enhances tumor accumulation of radioactivity and in vivo antitumor effect. In RIT with 211At, active targeting contributes to efficient tumor accumulation of radioactivity, resulting in a potent antitumor effect. SA-dependent protection that successfully maintains tumor targeting will facilitate the clinical application of alpha-RIT.
Many zinc (Zn) complexes have been developed as promising oral antidiabetic agents. In vitro assays using adipocytes have demonstrated that the coordination structures of Zn complexes affect the ...uptake of Zn into cells and have insulinomimetic activities, for which moderate stability of Zn complexes is vital. The complexation of Zn plays a major role improving its bioavailability. However, investigation of the speciation changes of Zn complexes after oral administration is lacking. A dual radiolabeling approach was applied in order to investigate the speciation of bis(5-chloro-7-iodo-8-quinolinolato)zinc complex Zn(Cq)2, which exhibits the antidiabetic activity in diabetic mice. In the present study, 65Zn- and 131I-labeled Zn(Cq)2 were synthesized, and their biodistribution were analyzed after an oral administration using both invasive conventional assays and noninvasive gamma-ray emission imaging (GREI), a novel nuclear medicine imaging modality that enables analysis of multiple radionuclides simultaneously. The GREI experiments visualized the behavior of 65Zn and 131ICq from the stomach to large intestine and through the small intestine; most of the administered Zn was transported together with clioquinol (5-chloro-7-iodo-8-quinolinol) (Cq). Higher accumulation of 65Zn for Zn(Cq)2 than ZnCl2 suggests that the Zn associated with Cq was highly absorbed by the intestinal tract. In particular, the molar ratio of administered iodine to Zn decreased during the distribution processes, indicating the dissociation of most Zn(Cq)2 complexes. In conclusion, the present study successfully evaluated the speciation changes of orally administered Zn(Cq)2 using the dual radiolabeling method.
All superheavy elements (SHEs), with atomic numbers (Z) ≥104, have been artificially synthesized one atom at a time and their chemical properties are largely unknown. Because these heavy nuclei have ...short lifetimes as well as extremely low production rates, chemical experiments need to be carried out on single atoms and have mostly been limited to adsorption and extraction. We have now investigated the precipitation properties of the SHE Rf (Z = 104). A co-precipitation method with samarium hydroxide had previously established that the co-precipitation behaviour of a range of elements reflected these elements' tendency to form hydroxide precipitates and/or ammine complex ions. Here we investigated co-precipitation of Rf in basic solutions containing NH
or NaOH. Comparisons between the behaviour of Rf with that of Zr and Hf (lighter homologues of Rf) and actinide Th (a pseudo-homologue of Rf) showed that Rf does not coordinate strongly with NH
, but forms a hydroxide (co)precipitate that is expected to be Rf(OH)
.
A one-pot three-component double-click process for preparing tumor-targeting agents for cancer radiotherapy is described here. By utilizing DOTA (or NOTA) containing tetrazines and the ...TCO-substituted aldehyde, the two click reactions, the tetrazine ligation (an inverse electron-demand Diels-Alder cycloaddition) and the RIKEN click (a rapid 6π-azaelectrocyclization), could simultaneously proceed under mild conditions to afford covalent attachment of the metal chelator DOTA or NOTA to biomolecules such as to albumin and anti-IGSF4 antibody without altering their activities. Subsequently, radiolabeling of DOTA- or NOTA-attached albumin and anti-IGSF4 antibody (an anti-tumor-targeting antibody) with
Cu, a β
-emitting radionuclide, could be achieved in a highly efficient manner via a simple chelation with DOTA proving to be a more superior chelator than NOTA. Our work provides a new and operationally simple method for introducing the
Cu isotope even in large quantities to biomolecules, thereby representing an important process for preparations of clinically relevant tumor-targeting agents for radiotherapy.
The nuclear isomer
178
Hf
m2
enables various investigations owing to its unique properties. To study exotic nuclear reactions induced by
178
Hf
m2
, an isomeric target is the most effective option in ...terms of luminosity. However, this creates many challenges to overcome. One of the challenges is that nanogram quantities of the isomer are essential for fabricating a target. We conducted a pilot experiment to establish the method for isomer production, as the first step toward large-scale production at the Radioactive Isotope Beam Factory (RIBF), RIKEN. An
α
beam at 40 MeV supplied from the AVF cyclotron bombarded natural-abundance metallic Yb foils. Hf isotopes were extracted from the irradiated target by a new chemical separation method. We produced a sample containing
10
11
atoms of
178
Hf
m2
, paving the way to future large-scale production at the RIBF.
Activation cross sections of α-particle induced reactions on natYb were measured. The stacked foil technique, the activation method and the γ-ray spectrometry were used. The stacked target consisted ...of natYb and natTi foils was irradiated with a 51.0-MeV α beam at the RIKEN AVF cyclotron. The γ rays emitted from the irradiated foils were measured using a high-resolution HPGe detector. Production cross sections of 170,171,172,173,175Hf, 171,172,173,177gLu and 169Yb were determined. The results were compared with previous experimental studies and theoretical calculations. For most of the reactions a consistent agreement was found.
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