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This study demonstrated the availability of an anion-exchange spin column method for the isolation of astatine-211 (211At) from bismuth (Bi). 211At was isolated in medium-to-excellent recovery efficiencies when loading 211At with 8M HCl (75.3–79.1%), and 8M HNO3 (35.9–54.3%). The processing time of the optimized protocol was about 40 minutes. A neutralized eluent afforded an 211At-labeled phenylalanine derivative even in the absence of oxidant (radiochemical yield: 75.4%). These results indicate the anion-exchange spin column is useful for the isolation of 211At and the following synthesis of astatinated compounds, which is the first to isolate 211At with an anion-exchange method.

211At was produced in the 209Bi(4He, 2n)211At reaction. The yield was separated from the irradiated bismuth target by a simple method, based on dry distillation. The optimized conditions of the method were studied by monitoring the astatine radioactivity with gamma-ray spectrometers. The no-carrier-added 211At solutions were prepared with eluents, namely distilled water, ethanol, methanol, or chloroform. Generally, the recovery yields obtained with the utilization of 1.6 mL of the eluent were 26–75%. The prepared 211At solutions were subjected to thin-layer chromatography and high-performance liquid chromatography to identify the chemical species present.

Background We recently reported a new absorbed dose conversion method, RAP (RAtio of Pharmacokinetics), for 211At-meta-astatobenzylguanidine (211At-MABG) using a single biodistribution measurement, the percent injected dose/g. However, there were some mathematical ambiguities in determining the optimal timing of a single measurement of the percent injected dose/g. Thus, we aimed to mathematically reconstruct the RAP method and to examine the optimal timing of a single measurement. Methods We derived a new formalism of the RAP dose conversion method at time t. In addition, we acquired a formula to determine the optimal timing of a single measurement of the percent injected dose/g, assuming the one-compartment model for biological clearance. Results We investigated the new formalism’s performance using a representative RAP coefficient with radioactive decay weighting. Dose conversions by representative RAP coefficients predicted the true [211At]MABG absorbed doses with an error of 10% or less. The inverses of the representative RAP coefficients plotted at 4 h post-injection, which was the optimal timing reported in the previous work, were very close to the new inverses of the RAP coefficients 4 h post-injection. Next, the behavior of the optimal timing was analyzed by radiolabeled compounds with physical half-lives of 7.2 h and 10 d on various biological clearance half-lives. Behavior maps of optimal timing showed a tendency to converge to a constant value as the biological clearance half-life of a target increased. The areas of optimal timing for both compounds within a 5% or 10% prediction error were distributed around the optimal timing when the biological clearance half-life of a target was equal to that of the reference. Finally, an example of RAP dose conversion was demonstrated for [211At]MABG. Conclusions The RAP dose conversion method renovated by the new formalism was able to estimate the [211At]MABG absorbed dose using a similar pharmacokinetics, such as [131I]MIBG. The present formalism revealed optimizing imaging time points on absorbed dose conversion between two radiopharmaceuticals. Further analysis and clinical data will be needed to elucidate the validity of a behavior map of the optimal timing of a single measurement for targeted alpha-nuclide therapy.

Purpose Therapeutic options for patients with malignant pheochromocytoma are currently limited, and therefore new treatment approaches are being sought. Targeted radionuclide therapy provides tumor-specific systemic treatments. The β-emitting radiopharmaceutical meta-131I-iodo-benzylguanidine (131I-MIBG) provides limited survival benefits and has adverse effects. A new generation of radionuclides for therapy using α-particles including meta-211At-astato-benzylguanidine (211At-MABG) are expected to have strong therapeutic effects with minimal side effects. However, this possibility has not been evaluated in an animal model of pheochromocytoma. We aimed to evaluate the therapeutic effects of the α-emitter 211At-MABG in a pheochromocytoma model. Methods We evaluated tumor volume-reducing effects of 211At-MABG using rat pheochromocytoma cell line PC12 tumor-bearing mice. PC12 tumor-bearing mice received intravenous injections of 211At-MABG (0.28, 0.56, 1.11, 1.85, 3.70 and 5.55 MBq; five mice per group). Tumor volumes were evaluated for 8 weeks after 211At-MABG administration. The control group of ten mice received phosphate-buffered saline. Results The 211At-MABG-treated mice showed significantly lower relative tumor growth during the first 38 days than the control mice. The relative tumor volumes on day 21 were 509.2% ± 169.1% in the control mice and 9.6% ± 5.5% in the mice receiving 0.56 MBq (p

Production cross sections of astatine isotopes 207−211At in the 29–57 MeV 7Li + natPb reaction have been measured by α- and γ-ray spectrometry. Excitation functions of production cross sections have been compared with a statistical calculation to study the reaction mechanism of the 7Li + natPb reaction. Production reactions of 207−211At in the 7Li + natPb have been derived. Considerably small experimental cross sections of 210At and 209At compared with the statistical calculation were clearly observed at incident energies higher than 44 MeV, indicating that the effects of breakup reaction play a role. A chemical separation of astatine from an irradiated lead target has been studied with a dry-distillation method. A complementary way to produce astatine isotopes has been developed.

α-Radiation effect on the solvent extraction of 241Am using the solution of N,N,N′,N′-tetraoctyldiglycolamide was investigated by means of the external and internal irradiation systems. In contrast to the internal irradiation system using an actinide radionuclide as an α-particles emitter, the external irradiation with 4He2+ ions provided by an accelerator can be carried out in a reasonable timescale and without contamination with radionuclides. No significant decrease in distribution ratio was observed even after irradiation over 200 kGy in both systems. It was also confirmed that the external irradiation system could be a useful alternative to the internal irradiation.

No-carrier-added 177Lu produced via the 176Yb(n, γ)177Yb → 177Lu process was separated from the macroscopic amounts of the Yb target using reversed-phase ion-pair liquid chromatography. To produce a highly purified 177Lu solution capable of labeling antibodies, the metallic impurities were removed using cation, chelating ion, and anion exchange columns. After the elimination of metallic impurities, the concentrations of Ca, Fe, and Zn were reduced from 87, 340, and 77 ppb to 13, 18, and 9 ppb, respectively. Consequently, the labeling yield of the 177Lu-labeled antibody increased from

Background: Amino-acid transporters are necessary for the tumour cell growth and survival, and have a crucial role in the development and invasiveness of cancer cells. But, it remains unclear about the prognostic significance of L-type amino-acid transporter 1 (LAT1), system ASC amino-acid transporter-2 (ASCT2), and xCT expression in patients with tongue cancer. We conducted the clinicopathological study to investigate the protein expression of these amino-acid transporters in tongue cancer. Methods: Eighty-five patients with surgically resected tongue cancer were evaluated. Tumour sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, 4F2hc/CD98hc (4F2hc), Ki-67, and microvessel density (MVD) determined by CD34, and p53. Results: L-type amino-acid transporter 1 and 4F2hc were highly expressed in 61% (52 out of 85) and 45% (38 out of 47), respectively. ASC amino-acid transporter-2 and xCT were positively expressed in 59% (50 out of 85) and 21% (18 out of 85), respectively. The expression of both LAT1 and ASCT2 was significantly associated with disease staging, lymph-node metastasis, lymphatic permeation, 4F2hc expression and cell proliferation (Ki-67). xCT expression indicated a significant association with advanced stage and tumour factor. By univariate analysis, disease staging, lymphatic permeation, vascular invasion, LAT1, ASCT2, 4F2hc, and Ki-67 had a significant relationship with overall survival. Multivariate analysis confirmed that LAT1 was an independent prognostic factor for predicting poor prognosis. Conclusions: L-type amino-acid transporter 1 and ASCT2 can serve as a significant prognostic factor for predicting worse outcome after surgical treatment and may have an important role in the development and aggressiveness of tongue cancer.

As part of basic studies on bifunctional chelating agents for 177Lu-labeled antibodies, 177Lu complexation of 1,4,7,10-tetraazacyclododecan-N,N´,N´´,N´´´-tetraacetic acid (DOTA) and diethylenetriamine-N,N,N´,N´´,N´´-pentaacetic acid (DTPA) was investigated in the presence of competing metals, including Ca(II), Fe(II), and Zn(II). It was found that DTPA is a better 177Lu complexation agent than DOTA in the presence of Ca(II), Fe(II), and Zn(II). Moreover, the elimination of Fe from the 177Lu solution proved especially effective because the DTPA comlexation of 177Lu was highly inhibited by Fe(II).

The radionuclide 67Cu was produced via the 68Zn(p,2p)67Cu reaction by irradiating enriched 68Zn targets with 70 MeV proton beam. Copper-67 was chemically separated from the zinc target by ion-exchange chromatography using Chelex-100 chelating ion-exchange resin. Procedure for recovery of the enriched 68Zn was developed. The target recovery yield of this method was evaluated to be more than 97%.

Background The expression of L-type amino acid transporter 1 (LAT1) has been described to play essential roles in tumor cell growth and survival. However, it remains unclear about the clinicopathological significance of LAT1 expression in biliary tract cancer. This study was conducted to determine biological significance of LAT1 expression and investigate whether LAT1 could be a prognostic biomarker for biliary tract cancer. Methods A total of 139 consecutive patients with resected pathologic stage I-IV biliary tract adenocarcinoma were retrospectively reviewed. Tumor specimens were stained by immunohistochemistry for LAT1, Ki-67, microvessel density determined by CD34, and p53; and prognosis of patients was correlated. Biological significance of LAT1 expression was investigated by in vitro and in vivo experiments with LAT inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) using cholangiocarcinoma cell line. Results In total patients, high LAT1 expressions were recognized in 64.0%. The expression of LAT1 was closely correlated with lymphatic metastases, cell proliferation and angiogenesis, and was a significant indicator for predicting poor outcome after surgery. LAT1 expression was a significant independent predictor by multivariate analysis. Both in vitro and in vivo preliminary experiments indicated that BCH significantly suppressed growth of the tumor and yielded an additive therapeutic efficacy to gemcitabine and 5-FU. Conclusions High expression of LAT1 is a promising pathological marker to predict the outcome in patients with biliary tract adenocarcinoma. Inhibition of LAT1 may be an effective targeted therapy for this distressing disease.

Endohedral 133Xe-higher fullerenes (133Xe@C76 and 133Xe@C84) were produced by implantation of 133Xe ions using an isotope separator. A high performance liquid chromatography (HPLC) analysis showed that the peak of endohedral 133Xe-higher fullerenes shifted backward from that of empty fullerenes, suggesting a possibility of the separation of endohedral 133Xe-higher fullerenes from empty fullerenes. The yields of endohedral 133Xe-fullerenes were in the order of 133Xe@C76