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The present study reports that the ground- and excited-state Re

Many scientists who are members of the Japan Society of Nuclear and Radiochemical Sciences have been involved in academic activities in response to the Fukushima Daiichi Nuclear Power Plant accident. Projects had been implemented that include determining radionuclides in environmental samples, identifying the distribution of radionuclides by large-scale soil monitoring, tracing radionuclide discharge time series, clarifying environmental dynamics of radionuclides, etc. For the last 10 years, these results have been shared and discussed in annual workshops partly sponsored by the society. This review summarizes the studies yielding these results, and they include reconstruction of the 131I distribution on soil by long-lived 129I analysis, reconstruction of the radioactive plume transport, identification of biological resuspension sources, discovery and characterization of cesium particles, and parameterization of the environmental behavior of radiocesium for dose assessment.

Purpose Fibroblast activation protein (FAP), which has high expression in cancer-associated fibroblasts of epithelial cancers, can be used as a theranostic target. Our previous study used 64Cu and 225Ac-labelled FAP inhibitors (FAPI-04) for a FAP-expressing pancreatic cancer xenograft imaging and therapy. However, the optimal therapeutic radionuclide for FAPI needs to be investigated further. In this study, we evaluated the therapeutic effects of beta-emitter (177Lu)-labelled FAPI-46 and alpha-emitter (225Ac)-labelled FAPI-46 in pancreatic cancer models. Methods PET scans (1 h post injection) were acquired in PANC-1 xenograft mice (n = 9) after the administration of [18F]FAPI-74 (12.4 ± 1.7 MBq) for the companion imaging. The biodistribution of [177Lu]FAPI-46 and [225Ac]FAPI-46 were evaluated in the xenograft model (total n = 12). For the determination of treatment effects, [177Lu]FAPI-46 and [225Ac]FAPI-46 were injected into PANC-1 xenograft mice at different doses: 3 MBq (n = 6), 10 MBq (n = 6), 30 MBq (n = 6), control (n = 4) for [177Lu]FAPI-46, and 3 kBq (n = 3), 10 kBq (n = 2), 30 kBq (n = 6), control (n = 7) for [225Ac]FAPI-46. Tumour sizes and body weights were followed. Results [18F]FAPI-74 showed rapid clearance by the kidneys and high accumulation in the tumour and intestine 1 h after administration. [177Lu]FAPI-46 and [225Ac]FAPI-46 also showed rapid clearance by the kidneys and relatively high accumulation in the tumour at 3 h. Both [177Lu]FAPI-46 and [225Ac]FAPI-46 showed tumour-suppressive effects, with a mild decrease in body weight. The treatment effects of [177Lu]FAPI-46 were relatively slow but lasted longer than those of [225Ac]FAPI-46. Conclusion This study suggested the possible application of FAPI radioligand therapy in FAP-expressing pancreatic cancer. Further evaluation is necessary to find the best radionuclide with shorter half-life, as well as the combination with therapies targeting tumour cells directly.

Objective Astatine (211At) is a promising alpha emitter as an alternative to iodine (131I). We are preparing the first-in-human (FIH) clinical trial of targeted alpha therapy for differentiated thyroid cancer in consultation with Pharmaceuticals and Medical Devices Agency. Here, we performed an extended single-dose toxicity examination under a reliability standard, as a preclinical safety assessment of [211At]NaAt to determine the FIH dose. Methods [211At]NaAt solution was injected into normal 6-week-old mice (male (n = 50) and female (n = 50), body weight: male 33.2 ± 1.7 g, female 27.3 ± 1.5 g), which were then divided into four groups: 5 MBq/kg (n = 20), 20 MBq/kg (n = 20), 50 MBq/kg (n = 30), saline control (n = 30). The mice were followed up for 5 days (primary evaluation point for acute toxicity: n = 80) or 14 days (n = 20: evaluation point for recovery) to monitor general condition and body weight change. At the end of the observation period, necropsy, blood test, organ weight measurement, and histopathological examination were performed. For body weight, blood test, and organ weight, statistical analyses were performed to compare data between the control and injected groups. Results No abnormal findings were observed in the general condition of mice. In the 50 MBq/kg group, males (days 3 and 5) showed a significant decrease in body weight compared with the control. However, necropsy did not differ significantly beyond the range of spontaneous lesions. In the blood test, males (50 MBq/kg) and females (50 MBq/kg) showed a decrease in white blood cell and platelet counts on day 5, and recovery on day 14. In the testis, a considerable weight decrease was observed on day 14 (50 MBq/kg), and multinucleated giant cells were observed in all mice, indicating a significant change related to the administration of [211At]NaAt. Conclusions In the extended single-dose toxicity study of [211At]NaAt, administration of high doses resulted in weight loss, transient bone marrow suppression, and pathological changes in the testis, which require consideration in the FIH clinical trial.

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 NH3 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 NH3, but forms a hydroxide (co)precipitate that is expected to be Rf(OH)4. It is difficult to investigate the chemical properties of superheavy elements, which are only available an atom at a time and rapidly decay. A co-precipitation method with samarium has now been developed that suggests rutherfordium would form hydroxide precipitates—but not ammine ones—if it were possible to perform these experiments on macroscopic quantities.

To investigate the chemical effect on the muon capture process through a muon transfer reaction from a muonic hydrogen atom, the formation rate of muonic carbon atoms is measured for benzene and cyclohexane molecules in liquid samples. The muon transfer rate to carbon atoms of the benzene molecule is higher than that to the carbon atoms of the cyclohexane molecule. Such a deviation has never been observed among those molecules for gas samples. This may be because the transfers occur from the excited states of muonic hydrogen atoms in the liquid system, whereas in the gas system, all the transfers occur from the 1s (ground) state of muon hydrogen atoms. The muonic hydrogen atoms in the excited states have a larger radius than those in the 1s state and are therefore considered to be affected by the steric hindrance of the molecular structure. This indicates that the excited states of muonic hydrogen atoms contribute significantly to the chemical effects on the muon transfer reaction.

α-Methyl-l-tyrosine (AMT) has a high affinity for the cancer-specific l-type amino acid transporter 1 (LAT1). Therefore, we established an anti-cancer therapy, with 211 At-labeled α-methyl-l-tyrosine (211 At-AAMT) as a carrier of 211 At into tumors. 211 At-AAMT had high affinity for LAT1, inhibited tumor cell growth, and induced DNA double-stranded breaks in vitro. We evaluated the accumulation of 211 At-AAMT in vivo and the role of LAT1. Treatment with 0.4 MBq/mouse 211 At-AAMT inhibited tumor growth in the PANC-1 tumor model and 1 MBq/mouse 211 At-AAMT inhibited metastasis in the lung of the B16F10 metastasis model. Our results suggested that 211 At would be useful for anti-cancer therapy and that LAT1 is suitable as a target for radionuclide therapy.

Phenylalanine derivatives, which target tumors especially through L-type amino acid transporter-1 (LAT1), have elicited considerable attention. In this study, we evaluated the treatment effect of phenylalanine labeled with the alpha emitter astatine (211At-PA) in tumor bearing mice. The C6 glioma, U-87MG, and GL261 cell lines were subjected to a cellular 211At-PA uptake analysis that included an evaluation of the uptake inhibition by the system L amino acid transporter inhibitor 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). BCH significantly inhibited para-211At-PA uptake in C6 glioma (12.2 ± 0.8%), U-87MG (27.6 ± 1.1%), and GL261 (12.6 ± 2.0%) cells compared to baseline, suggesting an uptake contribution by system L amino acid transporters. Subsequently, xenograft and allograft models were prepared by subcutaneously injecting C6 glioma (n = 12) or GL-261 cells (n = 12), respectively. C6 glioma mice received three 211At-PA doses (0.1, 0.5, or 1 MBq, n = 3/dose), while GL261 mice received one high dose (1 MBq, n = 7). 211At-PA exhibited a tumor growth suppression effect in C6 glioma models in a dose-dependent manner as well as in GL-261 models. This phenylalanine derivative labeled with astatine may be applicable as an alpha therapy that specifically targets system L amino acid transporters.

An elemental analysis method utilizing muons has been demonstrated to be effective for non-destructive and quantitative analysis of precious bulk materials. In muon capture process, molecular structure dependence was known, and this property has the potential to be used to identify chemical structure in addition to elemental composition. Before these potential applications, fundamental studies examining the muon capture process are necessary. In this study, muon capture ratios for two iron oxide compounds, which are both important in earth science, γ-Fe2O3 (maghemite) and Fe3O4 (magnetite), were measured. The measured muon capture ratios were A(Fe/O) = 2.34 ± 0.03 and A(Fe/O) = 2.77 ± 0.03 for γ-Fe2O3 and Fe3O4, respectively.

Chemical studies of transactinide elements (atomic number Z ≥ 104) are of great importance to understand the relativistic effects; however, the experimental methodology is limited owing to the sing...

Novel tetracyanidonitridorhenium(V) complexes with five-membered N-heteroaromatic ligands, (PPh4)2[ReN(CN)4L] [L = imidazole (Him) (2), 1-methylimidazole (Mim) (3), and pyrazole (pyz) (4)] and (PPh4)2[ReN(CN)4L]·L [L = Him (5) and Mim (6)], were synthesized by the reactions of (PPh4)2[ReN(CN)4] (1) with Him, Mim, and pyz, and their structures were determined by single-crystal X-ray analysis. The complexes 2, 3, 4, and 6 showed intense photoluminescence, with the emission quantum yields (Φem) being 0.65–0.75 in the solid state at 296 K. In contrast, the Φem and τem values of 5 are significantly smaller and shorter, respectively, than the relevant values of 2. The interconversion reactions among 1, 2, and 5 accompanied by large photoluminescence-intensity changes were accomplished by solvent-free reactions and exposure of water. The mechanochemical reaction of 2 with 1 mol equiv of Him in the solid state gave 5. Complex 5 was also obtained by the mechanochemical reaction of 1 with 2 mol equivalents of Him in the solid state. By placing solid of 5 in water, the solid showed intense photoluminescence to give 2. Complex 1 was produced under vacuum at 185 °C from 2 or 5.

Fibroblast activation protein (FAP), which promotes tumor growth and progression, is overexpressed in cancer-associated fibroblasts of many human epithelial cancers. Because of its low expression in normal organs, FAP is an excellent target for theranostics. In this study, we used radionuclides with relatively long half-lives, 64Cu (half-life, 12.7 h) and 225Ac (half-life, 10 d), to label FAP inhibitors (FAPIs) in mice with human pancreatic cancer xenografts. Methods: Male nude mice (body weight, 22.5 ± 1.2 g) were subcutaneously injected with human pancreatic cancer cells (PANC-1, n = 12; MIA PaCa-2, n = 8). Tumor xenograft mice were investigated after the intravenous injection of 64Cu-FAPI-04 (7.21 ± 0.46 MBq) by dynamic and delayed PET scans (2.5 h after injection). Static scans 1 h after the injection of 68Ga-FAPI-04 (3.6 ± 1.4 MBq) were also acquired for comparisons using the same cohort of mice (n = 8). Immunohistochemical staining was performed to confirm FAP expression in tumor xenografts using an FAP-α-antibody. For radioligand therapy, 225Ac-FAPI-04 (34 kBq) was injected into PANC-1 xenograft mice (n = 6). Tumor size was monitored and compared with that of control mice (n = 6). Results: Dynamic imaging of 64Cu-FAPI-04 showed rapid clearance through the kidneys and slow washout from tumors. Delayed PET imaging of 64Cu-FAPI-04 showed mild uptake in tumors and relatively high uptake in the liver and intestine. Accumulation levels in the tumor or normal organs were significantly higher for 64Cu-FAPI-04 than for 68Ga-FAPI-04, except in the heart, and excretion in the urine was higher for 68Ga-FAPI-04 than for 64Cu-FAPI-04. Immunohistochemical staining revealed abundant FAP expression in the stroma of xenografts. 225Ac-FAPI-04 injection showed significant tumor growth suppression in the PANC-1 xenograft mice, compared with the control mice, without a significant change in body weight. Conclusion: This proof-of-concept study showed that 64Cu-FAPI-04 and 225Ac-FAPI-04 could be used in theranostics for the treatment of FAP-expressing pancreatic cancer. α-therapy targeting FAP in the cancer stroma is effective and will contribute to the development of a new treatment strategy.

Elemental analysis based on muonic X-rays resulting from muon irradiation provides information about bulk material composition without causing damage, which is essential in the case of precious or otherwise unreachable samples, such as in archeology and planetary science. We developed a three-dimensional (3D) elemental analysis technique by combining the elemental analysis method based on negative muons with an imaging cadmium telluride double-sided strip detector (CdTe-DSD) designed for the hard X-ray and soft $$\gamma$$ γ -ray observation. A muon irradiation experiment using spherical plastic samples was conducted at the Japan Proton Accelerator Research Complex (J-PARC); a set of projection images was taken by the CdTe-DSD, equipped with a pinhole collimator, for different sample rotation angles. The projection images measured by the CdTe-DSD were utilized to obtain a 3D volumetric phantom by using the maximum likelihood expectation maximization algorithm. The reconstructed phantom successfully revealed the 3D distribution of carbon in the bulk samples and the stopping depth of the muons. This result demonstrated the feasibility of the proposed non-destructive 3D elemental analysis method for bulk material analysis based on muonic X-rays.

The deposition of insoluble radiocesium bearing microparticles (CsMPs), which were released from the Fukushima Daiichi Nuclear Power Plant (F1NPP) accident in March 2011, has resulted in the widespread contamination of eastern Japan. Obviously, these deposited insoluble CsMPs may become the secondary contamination sources by atmospheric migration or other environmental transferring process, however, the understanding of the transport mechanism remains non-elucidation, and the relevant evidence has not been directly provided. This study, for the first time, provides the direct evidence for the resuspension of these insoluble CsMPs to the atmosphere from 1) proximity of 137Cs radioactivity and resemblance of the morphology and the elemental compositions of CsMPs in the samples of soil and aerosol derived from the same sampling site, 2) the special characteristics of the resuspended CsMPs of which the ratios of Na/Si, K/Si and/or Cs/Si were smaller than those from the initially released CsMPs collected at either long distance or near F1NPP, which can be ascribed to the slowly natural corrosion of CsMPs by the loss of the small amount of soluble contents in CsMPs and 3) high CsMPs concentration of 10 granules/gram in the surface soil of our sampling site and the observed resuspension of surface soil dust at wind gust speed higher than 4 m s-1. Specifically, fifteen single CsMPs were successfully isolated from the aerosol filters collected by unmanned high-volume air samplers at a severely polluted area in Fukushima Prefecture, about 25 km away from F1NPP, from January 2015 to September 2019. The mean diameter of these CsMPs was 1.8 ± 0.5 μm, and the average 137Cs radioactivity was 0.35 ± 0.23 Bq/granule. The contribution rate of the resuspended CsMPs to the atmospheric radiocesium was estimated from the ratio of 137Cs radioactivity of a single CsMP to that of the aerosol filter to be of 23.9 ± 15.3%. There has been no considerable decreasing trend in the annual CsMP resuspension frequency.

Background 211At is a high-energy α-ray emitter with a relatively short half-life and a high cytotoxicity for cancer cells. Its dispersion can be imaged using clinical scanners, and it can be produced in cyclotrons without the use of nuclear fuel material. This study investigated the biodistribution and the antitumor effect of 211At-labeled gold nanoparticles (211At-AuNP) administered intratumorally. Results AuNP with a diameter of 5, 13, 30, or 120 nm that had been modified with poly (ethylene glycol) methyl ether (mPEG) thiol and labeled with 211At (211At-AuNP-S-mPEG) were incubated with tumor cells, or intratumorally administered to C6 glioma or PANC-1 pancreatic cancers subcutaneously transplanted into rodent models. Systemic and intratumoral distributions of the particles in the rodents were then evaluated using scintigraphy and autoradiography, and the changes in tumor volumes were followed for about 40 days. 211At-AuNP-S-mPEG was cytotoxic when it was internalized by the tumor cells. After intratumoral administration, 211At-AuNP-S-mPEG became localized in the tumor and did not spread to systemic organs during a time period equivalent to 6 half-lives of 211At. Tumor growth was strongly suppressed for both C6 and PANC-1 by 211At-AuNP-S-mPEG. In the C6 glioma model, the strongest antitumor effect was observed in the group treated with 211At-AuNP-S-mPEG with a diameter of 5 nm. Conclusions The intratumoral single administration of a simple nanoparticle, 211At-AuNP-S-mPEG, was shown to suppress the growth of tumor tissue strongly in a particle size-dependent manner without radiation exposure to other organs caused by systemic spread of the radionuclide. Graphic Abstract

Purpose Compared to a conventional beta-emitter 131I, an alpha-emitter 211At can have a stronger treatment effect against differentiated thyroid cancer. However, its therapeutic advantage has not been fully elucidated. Thus, here, we compared the therapeutic effect of [211At]NaAt with that of [131I]NaI. Methods In vitro observation of double-stranded breaks (DSBs) and colony formation assays were performed in K1-NIS cells. The biodistribution of [131I]NaI and [211At]NaAt was measured in K1-NIS xenograft mice at 3 and 24 h (n=12). The treatment effect was compared between [131I]NaI and [211At]NaAt in K1-NIS xenograft mice using different radioactivities for each solution (1 (n=4), 4 (n=4), and 8 MBq (n=4) of [131I]NaI and 0.4 (n=7), 0.8 (n=9), and 1.2 MBq (n=4) of [211At]NaAt).Results 211At caused more DSBs in K1-NIS cells and had a greater inhibitory effect on colony formation than 131I. In K1-NIS xenograft mice, the uptake of [131I]NaI in the thyroid gland was significantly higher than that of [211At]NaAt. In other organs and tumours, the uptake of [211At]NaAt was significantly higher than that of [131I]NaI. While both [211At]NaAt and [131I]NaI showed dose-dependent therapeutic effects, [211At]NaAt showed a stronger tumour-suppressive effect. Tumour regrowth was suppressed until 18, 25, and 46 days after 0.4, 0.8, and 1.2 MBq [211At]NaAt administration, respectively, whereas it was observed within 0–12 days after [131I]NaI administration (1, 4, and 8 MBq).Conclusions The stronger tumour-suppressive effect of [211At]NaAt solution supports the promising clinical application of [211At]NaAt therapy in patients with iodine-avid thyroid cancer refractory to [131I]NaI treatment.

Variations in isotopic abundance provide useful information for various scientific fields. Herein we performed a feasibility study by non-destructive isotopic analysis of negative muons. We irradiated two lead plate samples, one with the natural isotopic composition and one enriched with 208Pb, with negative muons and observed the gamma rays from 208Tl with a half-life of 3 min generated via muon absorption by 208Pb during muon irradiation. The isotopic abundance of 208Pb in natPb was successfully determined without sample destruction from the gamma ray intensity to be 69%, which agreed well with the mass spectrometry results.

We have developed a new method for producing 191Pt from an iridium target. Alkali fusion of iridium was successfully performed using a vertical beam irradiation method and a mixed target of Ir and Na2O2, which resulted in easy dissolution of the irradiated iridium target. A trace amount of PtⅣCl62- was isolated from bulk IrⅣCl62- by solvent extraction and anion exchange chromatography. The production yield of 191Pt was 7.1 ± 0.4 (MBq/μA h, EOB) by proton irradiation at 30 MeV. The radioplatinum product (n.c.a.) was prepared at a radiochemical purity of 97% for PtⅣCl62-, and 95% for PtⅡCl42-, respectively.

Background The α-emitting radionuclide radium-223 (223Ra) is widely used for the treatment of bone metastasis in patients with castration-resistant prostate cancer. However, 223Ra decays into radon-219 (219Rn) which is a noble-gas isotope, and 219Rn may escape from patients treated with 223Ra via their respiration. In this study, we quantified the amount of 219Rn contained in the breath of patients treated with 223Ra to estimate its effect on the internal exposure dose of caregivers. Methods A total of 12 breath samples were collected using a breath collection bag from a total of six patients treated with 223RaCl2. Approximately 300 mL of exhaled breath was collected in a breath bag at 1 min and at 5 min after the start of 223RaCl2 administration. The contents of each bag were measured using an HPGe detector, and the amount of 219Rn was quantified based on the detection of the γ peak of 211Bi, which is a descendant nuclide of 219Rn, persisting in the breath bag. The effective dose to caregivers arising from the inhalation of 219Rn was estimated by referring to the scenario for the calculation of release criteria established for 131I therapy in Japan. Results A small peak for the 351-keV γ ray of 211Bi originating from the exhalation of 219Rn was observed. Using the observed γ peak of 211Bi, the average amounts of 219Rn per unit breath volume at 1 min and 5 min after the start of 223RaCl2 administration were calculated as 90 ± 56 Bq/mL and 28 ± 9 Bq/mL, respectively. The effective dose of 219Rn to caregivers was estimated to be 3.5 μSv per injection. Conclusions The amount of 219Rn in the exhaled breath of patients treated with 223RaCl2 was quantitatively calculated using breath collection bags. The internal radiation exposure of caregivers from 219Rn in the exhaled breath of patients treated with 223RaCl2 is relatively small.

The Fukushima Daiichi Nuclear Power Plant (FDNPP) accident released abundant radioactive particles into the surrounding environment. Herein, we analyzed the activity of 90Sr in these particles to estimate the contribution of this radionuclide to the overall radiation exposure and shed light on the processes that occurred during the accident. Seven radioactive particles were isolated from the dust and soil samples collected from areas surrounding the FDNPP, and the minimum/maximum 137Cs activities were determined as 224/4,100 Bq. Based on the size, specific activity, and 134Cs/137Cs activity ratios, we concluded that six of the seven radioactive particles were released from the Unit 1 reactor, while one particle was released from the Unit 3 reactor by a hydrogen explosion. Strontium-90 was detected in all radioactive particles, and the minimal/maximal 90Sr activities were determined as 0.046/1.4 Bq. 137Cs/90Sr activity ratios above 1000 were observed for all seven particles, that is, compared to 137Cs, 90Sr had negligible contribution to the overall radiation exposure. The 137Cs/90Sr activity ratios of the radioactive particles were similar to those of terrestrial environmental samples and were higher for particles released from the Unit 1 reactor than for samples collected from the Unit 1 reactor building, which indicates possibility of additional 90Sr-rich contamination after release of the particles.

Elemental isotopic ratios are measured in various research fields and provide useful information regarding age, origin, geological and biological activities, ancient climate, etc. Here, we report a new isotopic analysis method without sample destruction using muon-induced characteristic X-rays. We demonstrated this method by conducting muon-beam irradiation experiments on two Pb plates with different isotopic ratios: natural isotopic composition and artificially enriched 208Pb. The observed broad X-ray peaks of the Pb Kα line around 6 MeV were deconvolved with 206Pb, 207Pb, and 208Pb isotopes, giving the isotopic ratios. The resulting isotopic ratios were consistent with those obtained from mass spectrometry.

The role of valence electrons for the muon capture process by molecules is experimentally investigated with the aid of cascade calculations. Low-momentum muons are introduced to gas targets of CO, CO2, and COS below atmospheric pressure. The initial states of captured muons are determined from the measured muonic X-ray structure of the Lyman and Balmer series. We propose that the lone pair electrons in the carbon atom of CO significantly contribute to the capture of a muon with large angular momenta.

金沢大学疾患モデル総合研究センター, Alpha particle-emitting radionuclides have gained considerable attention for radionuclide therapy. Astatine-211 ( 211 At) is a promising alpha particle-emitting radionuclide. 211 At is a halogen that has similar chemical properties to iodine and exhibits a half-life of 7.2 h. However, direct labeling of proteins or peptides into the tyrosine residue with 211 At was shown to be impractical. Herein, we demonstrate a novel 211 At-labeling method using the RGD peptide as a model peptide. An 211 At-labeled RGD peptide, [ 211 At]c[RGDf(4-At)K], was prepared from a precursor with a tributylstannyl group on the phenylalanine residue in c(RGDfK) with a radiochemical yield of 63% and a radiochemical purity of >96%, and its potential for targeted radionuclide therapy was evaluated. Based on the results of biodistribution experiments, [ 125 I]c[RGDf(4-I)K] and [ 211 At]c[RGDf(4-At)K] showed high accumulation in the tumor and similar biodistribution. This study provides useful information for radiotheranostics between an 211 At-labeled peptide and the corresponding radioiodine-labeled peptide. © 2019 American Chemical Society., This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.

211At is an α-emitter that has similar chemical properties to iodine and is used in targeted α-therapy. In the present study, we added ascorbic acid (AA) to 211At solution to increase the radiochemical purity of astatide and evaluated its efficacy against differentiated thyroid cancer, which is characterized by the expression of sodium/iodide symporter (NIS). Methods: Crude 211At solution (AA(−)) and 211At solution treated with AA (AA(+)) were prepared. Uptake by the thyroid was compared between the 2 solutions in normal male Wistar rats (n = 6). Cellular uptake in K1-NIS cells was analyzed under the AA(+) and AA(−) conditions. AA(+) was injected at 3 doses into K1-NIS xenograft mice: 1 MBq (n = 6), 0.4 MBq (n = 6), and 0.1 MBq (n = 6), and vehicle was injected into control mice (n = 6). The treatment effects were compared among the 4 groups. Results: Uptake by the thyroid was significantly enhanced in rats injected with the AA(+) as compared with those injected with AA(−). Cellular uptake analysis showed significantly increased uptake of 211At by the K1-NIS cells under the AA(+) condition as compared with the AA(−) condition. In the mouse xenograft model, the K1-NIS tumors showed significant accumulation of 211At at 3 and 24 h after administration (22.5 ± 10.4 and 12.9 ± 6.8 percentage injected dose, respectively). Tumor growth was immediately inhibited in a dose-dependent manner after administration of 211At. In the survival analysis, the 211At groups (0.1, 0.4, and 1 MBq) showed significantly better survival than the control group. Conclusion: Uptake of 211At was enhanced in differentiated thyroid cancer cells as well as the normal thyroid using 211At solution treated with AA. The method also showed dose-dependent efficacy against the K1-NIS xenografts, suggesting its potential applicability to targeted α-therapy.

The first thiohalide μ3-capped octahedral hexanuclear technetium clusters with 24 valence electrons, [Tc6(μ3-S)8−n(μ3-Br)nBr6]n−4 [n = 1 ([Tc-S7Br]3−) and n = 2 ([Tc-S6Br2]2−)] and [Tc6(μ3-S)7(μ3-Cl)Cl6]3− ([Tc-S7Cl]3−), were synthesized and characterized. The structures of [Tc-S7Br]3−, [Tc-S6Br2]2−, and [Tc-S7Cl]3− were determined by single-crystal X-ray analysis. The Tc–Tc bond distances in [Tc-S7Br]3−, [Tc-S6Br2]2−, and [Tc-S7Cl]3− are 2.5842(6)–2.6029(6) A (avg. 2.593(2) A), 2.5835(10)–2.6049(10) A (avg. 2.596(1) A), and 2.5829(4)–2.5940(4) A (avg. 2.587(3) A), respectively. The capping halide and sulfide ligands in [Tc-S7Br]3−, [Tc-S6Br2]2−, and [Tc-S7Cl]3− were disordered in the crystals. The bond distances of Tc–S/Br as a function of the occupancies of the capping bromides for [Tc-S6Br2]2−, [Tc-S7Br]3−, and [Tc6(μ3-S)8Br6]4− ([Tc-S8]4−) showed a linear correlation. The one-electron reduction waves assignable to the TcIII6/TcIITcIII5 [Tc6(24e/25e)] process were observed for the novel complexes. Density functional theory (DFT) calculations of the hexanuclear technetium complexes showed a smaller energy gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of the hexanuclear technetium complexes compared to those of the rhenium analogues. The electronic transitions of the new technetium complexes shifted to lower energy compared to the isotypic rhenium complexes.

Per-atom muon capture ratios are precisely determined from characteristic muonic X-ray measurements of three nitrogen oxide samples (NO, N2O, and NO2) at pressures below 100 kPa. A higher density of covalent electrons at the N atoms relative to the O atoms is required if we explain the experimental results using the proposed muon capture models. From molecular orbit calculations, we found that the electron distributions of only the highest occupied molecular orbitals (HOMO) are dominant at the N atoms, and the electrons in the HOMO significantly contribute to the muon capture phenomena in the nitrogen oxide molecules.