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高井 俊秀; 古川 智弘; 渡辺 茂樹*; 石岡 典子*
Mechanical Engineering Journal (Internet), 9(4), p.21-00397_1 - 21-00397_11, 2022/08
がん治療用放射性医薬品として期待されているアスタチン211の量産技術として、量子科学技術研究開発機構において、革新的な"液体ビスマス標的システム"が考案された。このシステムを実現するためには、非常に腐食性の高いビスマス環境下で使用できる高耐食性標的窓が必要となる。この要請にこたえ、われわれは、高速炉および加速器駆動未臨界炉開発の一環として実施された鉛ビスマス環境下での材料腐食の知見に基づき、液体標的窓材を選定するための材料腐食試験を飽和溶存酸素条件下と低酸素濃度条件下で実施し、その腐食挙動を調べた。この結果、FeCrAl合金は優れた耐食性を示し、FeCrMo合金はこれに続いた。これら材料については液体標的窓材に適していると考えられる。
篠原 彩花*; 花岡 宏史*; 坂下 哲哉*; 佐藤 達彦; 山口 藍子*; 石岡 典子*; 対馬 義人*
Annals of Nuclear Medicine, 32(2), p.114 - 122, 2018/02
被引用回数：8 パーセンタイル：44.01(Radiology, Nuclear Medicine & Medical Imaging)オージェ放出核種を用いた放射線治療は、高い治療効果と低い正常組織反応を期待できる。本研究では、オージェ放出核種
Iと
線放出核種
Iを2次元と3次元の培養細胞に取り込ませて、その細胞致死率を測定した。また、粒子・重イオン輸送計算コードPHITSを用いて、各条件に対する細胞の吸収線量分布を精度よく計算し、細胞生存率と吸収線量の関係について評価した。その結果、I治療はI治療と比較して、2次元培養細胞の場合はほぼ同程度の効果が得られるが、3次元培養細胞の場合は治療効果が低いことが分かった。これは、クロスファイア効果と呼ばれる一本の線が複数の細胞をヒットする効果と、薬剤が培養細胞内に均一に分布しない効果に起因すると考えられる。
evaluation of F(
-I)KCCYSL for targeting HER2佐々木 一郎; 渡辺 茂樹; 大島 康宏; 須郷 由美; 山田 圭一*; 花岡 宏史*; 石岡 典子
Peptide Science 2015, p.243 - 246, 2016/03
Radioisotope labeled peptides with high affinity to receptors overexpressing on the surface of tumor cells are promising for applications in nuclear medicine such as diagnostic radiography and radiotherapy. Radiohalogens such as I and 
At are useful for clinical imaging and therapeutic applications, and it can be introduced at the 
position of phenylalanine residue via electrophilic destannylation. KCCYSL (Lys
-Cys
-Cys
-Tyr
-Ser
-Leu
) is a hexapeptide containing disulfide bond. Previous study revealed that KCCYSL has potential as tumor imaging and therapeutic agent targeting tumor cells overexpressing the human epidermal growth factor receptor type 2 (HER2). In this study, we report synthesis and evaluation of radiohalogenated KCCYSL derivatives. Precursor peptides, Boc-F(-SnBu
)K(Boc)C(Trt)C(Trt)Y(
Bu)S(Bu)L-OH and Boc-F(-SnBu)GS(Bu)GK(Boc)C(Trt)C(Trt)Y(Bu)S(Bu)L-OH, were synthesized by the Fmoc solid phase peptide synthesis. Then, precursor peptides were radioiodinated via electrophilic destannylation, and they were deprotected to obtain F(-I)KCCYSL and F(-I)GSGKCCYSL in radiochemical yield 15% and 17%, respectively. 
assays of the radioiodinated peptides for HER2 and stability in serum are being undertaken.
森 勝伸*; 佐柄 克哉*; 新井 香織*; 中谷 暢丈*; 大平 慎一*; 戸田 敬*; 板橋 英之*; 小崎 大輔*; 須郷 由美; 渡辺 茂樹; et al.
Journal of Chromatography A, 1431, p.131 - 137, 2016/01
被引用回数：10 パーセンタイル：41.68(Biochemical Research Methods)Selective separation and sensitive detection of dissolved silicon and boron (DSi and DB) in aqueous solution was achieved by connecting an electrodialytic ion isolation device (EID), an ion-exclusion chromatography (IEC) column, and a corona charged aerosol detector (CCAD) in sequence. They were separated by IEC using pure water eluent. Detection of DSi and DB by the CCAD was effective for much greater sensitivity than by conductimetric detection. The EID removed salt from the sample prior to the IEC-CCAD. The combination of EID, IEC and CCAD successfully separated and determined DSi and DB in artificial seawater and hot-spring water samples by eluting pure water.
Li + 
Pb reaction西中 一朗; 横山 明彦*; 鷲山 幸信*; 前田 英太*; 渡辺 茂樹; 橋本 和幸; 石岡 典子; 牧井 宏之; 豊嶋 厚史; 山田 記大*; et al.
Journal of Radioanalytical and Nuclear Chemistry, 304(3), p.1077 - 1083, 2015/06
被引用回数：9 パーセンタイル：60.64(Chemistry, Analytical)29-57MeVのLiビームとPb標的核の反応においてアスタチン同位体
Atの生成断面積を
線, 
線スペクトルメトリーで測定した。生成断面積の励起関数を統計模型モデル計算と比較することで、Li + Pbの反応機構を調べた。44MeVより大きい入射エネルギーでの
Atと
Atの生成断面積が理論値よりも小さいことから、分解反応が存在することを明らかにした。照射した鉛標的からのアスタチンの化学分離を乾式蒸留法に基づいて調べ、アスタチン製造の相補的な手法を開発した。
Br--methyl-phenylalanine for tumor PET imaging花岡 宏史*; 大島 康宏; 鈴木 結利花*; 山口 藍子*; 渡辺 茂樹; 上原 知也*; 永森 收志*; 金井 好克*; 石岡 典子; 対馬 義人*; et al.
Journal of Nuclear Medicine, 56(5), p.791 - 797, 2015/05
被引用回数：18 パーセンタイル：62.62(Radiology, Nuclear Medicine & Medical Imaging)Radiolabeled amino acids are superior PET tracers for imaging of malignant tumors, and amino acids labeled with Br, an attractive positron emitter due to its relatively long half-life (t
=16.2 h), could potentially be widely usable tumor imaging tracer. In this study, in consideration of stability and tumor specificity, 2-Br-bromo--methyl-L-phenylalanine (2-Br-BAMP) and 4-Br-bromo--methyl-L-phenylalanine (4-Br-BAMP) were designed and their potential as a tumor imaging agent was evaluated. No-carrier-added Br and 
Br, the latter of which is suitable radiobromine for basic studies due to its longer half-life (t = 57.1 h), were produced. Both Br-BAMPs were stable in the plasma and in the murine body. In biodistribution studies, 2-Br-BAMP showed more rapid blood clearance and lower renal accumulation than did 4-Br-BAMP. More than 90% of injected radioactivity was excreted in the urine by 6 h post-injection of 2-Br-BAMP. High tumor accumulation of 2-Br-BAMP was observed in tumor-bearing mice and PET imaging with 2-Br-BAMP enabled clear visualization of the tumor. These findings suggest that 2-Br-BAMP would constitute a potential new PET tracer for tumor imaging and may eventually enable the wider use of amino acid tracers.
evaluation of 
Cu-labeled peptide for tumor imaging須郷 由美; 佐々木 一郎; 渡辺 茂樹; 大島 康宏; 石岡 典子
JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 100, 2015/03
MARSGL peptide (H-Met-Ala-Arg-Ser-Gly-Leu-OH) has high affinity to the human epidermal growth factor receptor 2 (HER2) overexpressing in various tumor cells. Copper-64 (Cu) is a useful radionuclide in nuclear medicine, and can be produced by the cyclotron. In this study, we designed and synthesized Cu-labeled MARSGL peptide conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) as a novel positron emission tomography (PET) imaging probe for HER2 overexpressing tumors. The formation of Cu-DOTA-MARSGL was determined by TLC and HPLC compared with a non-radioactive preparation. It was confirmed that Cu-DOTA-MARSGL was obtained in high radiochemical yield more than 94%. We also examined a stability of Cu-DOTA-MARSGL . The chromatogram was not changed after incubation in physiological saline at 37
C overnight. In order to evaluate the usefulness as a PET imaging probe, further studies on the stability in human or mice plasma and the cellular uptake are in progress.
渡辺 智; 橋本 和幸; 石岡 典子
JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 102, 2015/03
As part of basic studies for the production of 
Lu capable of labeling of Lu-1,4,7,10-tetraazacyclododecan-N,N',N'',N'''-tetraacetic acid (DOTA)-antibody, Lu complexation of DOTA and diethylenetriamine-N,N,N',N'',N''-pentaacetic acid (DTPA) was investigated in the presence of competing metals: Mg, Cu, and Yb in addition to Ca, Fe, and Zn. The inhibition of Lu complexation by the competing metals was in the order of Mg, Ca 
Fe Yb Cu, Zn and Mg, Ca Zn Fe Cu Yb with DOTA and DTPA, respectively. Consequently, the elimination of Mg and Ca from the Lu final solution produced was not found to be necessary, while the elimination of Cu, Fe, Zn and Yb from the Lu final solution was found to be necessary. On the basis of the knowledge obtained, the method of elimination of the competing metals will be developed.
studies on cellular binding and stability of Cu-labeled peptide for tumor imaging須郷 由美; 大島 康宏; 佐々木 一郎; 石岡 典子
Peptide Science 2014, p.303 - 306, 2015/03
In the previous study, we have designed and synthesized Cu-DOTA-MARSGL as a novel positron emission tomography (PET) imaging probe for the human epidermal growth factor receptor 2 (HER2) overexpressing tumors. In order to evaluate the usefulness as a PET imaging probe, further studies on the cellular binding and the stability in human or murine plasma were carried out in this work. In the cellular binding assay, it was observed that the radioactivity bound to the cells was dependent on the HER2 expression level. This result suggests the HER2 specificity of Cu-DOTA-MARSGL. It was also confirmed that Cu-DOTA-MARSGL had high stability in saline, while it had low stability in plasma. The degradation product was analyzed by LC/MS using a non-radioactive preparation. The main peak in the chromatogram after incubation in plasma was assigned to Cu-DOTA-MA, which was formed by an endogenous peptidase. To increase the resistance to the peptidase, a modification of the structure is in progress.
佐々木 一郎; 花岡 宏史*; 山田 圭一*; 渡辺 茂樹; 須郷 由美; 大島 康宏; 鈴木 博元; 石岡 典子
Peptide Science 2014, p.257 - 260, 2015/03
We have sought to establish drug discovery system using radioisotope (RI) labeled peptides which have high affinity to target proteins overexpressed in cancers. Of the target proteins, we chose the human epidermal growth factor receptor type 2 (HER2), a membrane protein overexpressed in various cancers to evaluate the drug discovery system. Three series of random hexapeptide libraries introduced a radioiodinated D-tyrosine (y(3-I)) to 
-terminal were designed and binding assay with HER2-expressed cell lines were conducted in this study. First, we synthesized a series of random hexapeptide libraries with fixed amino acid sequence at 1 and 2 positions, y(3-I)XXXXXX. Non-radioactive random peptide libraries, yXXXXXX, were prepared by Fmoc-SPPS with an automatic peptide synthesizer. Radioiodinated y(3-I)XXXXXX were subsequently synthesized in 30-50% radiochemical yield. Binding assay using HER2-overexpressed cell line showed that high affinity (38-50% dose, n=6) was obtained with yIIXXXX, while other random peptide libraries were yielded low affinity (approximately 1% dose), which indicated that the system using RI labeled random peptide libraries have potential to discover peptide drug for cancer therapy. Preparation of other random hexapeptide libraries are being undertaken.
渡辺 智; 橋本 和幸; 石岡 典子
Journal of Radioanalytical and Nuclear Chemistry, 303(2), p.1519 - 1521, 2015/02
被引用回数：10 パーセンタイル：60.64(Chemistry, Analytical)がん治療に有用な線放出核種であるLu(半減期6.7日)の製造研究(
Yb(n,) Yb(T=1.911 h)
Lu)において、抗体標識に用いる二官能性キレート剤とLuとの錯形成時に、Ca, Fe及びZn等の金属元素が存在すると、錯形成の阻害が起こることを明らかにしている。ただし、Ca, Fe及びZnの存在量や、二官能性キレート剤の種類による阻害についての詳細は分かっていない。そこで、本研究では、DOTA及びDTPAとLuとの錯形成において、Ca, Fe又はZnを加えたときの影響について調べた。Lu溶液とCa(II), Fe(II)又はZn(II)溶液との混合溶液に、酢酸バッファーを加えた後、DOTA又はDTPA溶液を加えてLu-DOTA又はLu-DTPAを作製し、薄層クロマトグラフィーにより錯形成率を求めた。結果として、Ca, Fe又はZnの存在度が増加するに従いLuの錯形成率は減少し、また、DOTAよりもDTPAのほうがLuの錯形成率が高いことがわかった。以上から、抗体標識に用いる二官能性キレート剤として、DOTAよりもDTPAのほうがLuとの錯形成は有利であることが示唆された。
-radiation effect on solvent extraction of minor actinide須郷 由美; 佐々木 祐二; 田口 光正; 石岡 典子
Journal of Radioanalytical and Nuclear Chemistry, 303(2), p.1381 - 1384, 2015/02
被引用回数：4 パーセンタイル：25.85(Chemistry, Analytical)-Radiation effect on the extraction of 
Am was investigated using the solution of 
-tetraoctyldiglycolamide pre-irradiated with -particles provided by a tandem accelerator, in contrast to the irradiation using actinides as an -particles emitter. Am was extracted almost quantitatively from the aqueous phase into the organic one. The concentration in the organic phase nearly kept constant even after irradiation with -rays.
Lu for radioimmunotherapy渡辺 智; 橋本 和幸; 渡辺 茂樹; 飯田 靖彦*; 花岡 宏史*; 遠藤 啓吾*; 石岡 典子
Journal of Radioanalytical and Nuclear Chemistry, 303(1), p.935 - 940, 2015/01
被引用回数：11 パーセンタイル：67.3(Chemistry, Analytical)No-carrier-added Lu produced via the Yb(n, ) Yb Lu process was separated from the macroscopic amounts of the Yb target using reversed-phase ion-pair liquid chromatography. To produce a highly purified Lu 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 Lu -labeled antibody increased from less than 5% to 88%.
Cu produced by 
Z(
,
) reaction using 
C(
,) neutrons佐藤 望; 塚田 和明; 渡辺 智; 石岡 典子; 川端 方子; 佐伯 秀也; 永井 泰樹; 金 政浩*; 湊 太志; 岩本 信之; et al.
Journal of the Physical Society of Japan, 83(7), p.073201_1 - 073201_4, 2014/07
被引用回数：13 パーセンタイル：64.07(Physics, Multidisciplinary)本研究により、Zn(,)Cu反応で生成される医療用放射性同位体Cuは、従来法による製造と比較して放射核的純度が非常に高いことが初めて明らかになった。実験は原子力機構高崎研究所のイオン照射研究施設において行われ、中性子源としてエネルギー41MeVの重陽子ビームによるC(d,n)反応が用いられた。中性子照射後、高純度Ge検出器を用いて濃縮Zn試料の線測定を行い、その結果から核反応生成物の放射能を評価した。生成されたCuに対する不純物核種の量は非常に少ないため、ZnからCuを化学分離する過程の簡略化や、高価な濃縮Zn試料の再利用が期待される。この研究結果は、高純度Cu製造に最適な反応系としてZn(,)Cu反応を提案するものであり、Cuの製造法に関する長年の課題を解決できる可能性がある。
石岡 典子
放射線と産業, (136), p.4 - 8, 2014/06
「放射線と産業」136号にて特集する「RIを用いたがんの診断・治療薬開発の最前線」において、RI薬剤が可能にする精確ながん診断やQOLの高いがん治療について、イオンビームや中性子を利用したRIの製造から標識化合物の合成、薬剤化に向けた生物学的検討を示し、RI薬剤開発の全貌について研究成果を中心に解説する。
豊田 実*; 解良 恭一*; 大島 康宏; 石岡 典子; 紫野 正人*; 坂倉 浩一*; 高安 幸弘*; 高橋 克昌*; 富永 英之*; 織内 昇*; et al.
British Journal of Cancer, 110(10), p.2506 - 2513, 2014/05
被引用回数：106 パーセンタイル：95.14(Oncology)Amino-acid transporters are necessary for the tumor cell growth and survival, and play a crucial role in the development of cancer. 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. Eighty-five patients with surgically resected tongue cancer were evaluated. Tumor sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, CD98, Ki-67, CD34 and p53. The expression of LAT1 and ASCT2 was significantly associated with disease staging, lymph node metastasis, lymphatic permeation, vascular invasion, CD98 expression and cell proliferation (Ki-67). xCT expression indicated a significant association with advanced stage and tumor factor, correlated with CD98. By univariate analysis, both LAT1 and ASCT2 had a significant relationship with prognosis. Multivariate analysis confirmed that LAT1 were independent prognostic factors for predicting poor prognosis. These results suggest that LAT1 and ASCT2 can serve as a significant prognostic factor for predicting worse outcome after surgical treatment and may play an important role in the development and pathogenesis for tongue cancer.
-methyltyrosine (FAMT) uptake on PET in patients with oesophageal cancer鈴木 茂正*; 解良 恭一*; 大島 康宏; 石岡 典子; 宗田 真*; 横堀 武彦*; 宮崎 達也*; 織内 昇*; 富永 英之*; 金井 好克*; et al.
British Journal of Cancer, 110(8), p.1985 - 1991, 2014/04
被引用回数：24 パーセンタイル：60.43(Oncology)Fluorine-18--methyltyrosine (FAMT) as an amino acid tracer for positron emission tomography (PET) is useful for detecting human neoplasms. FAMT is accumulated in tumor cells solely via L-type amino acid transporter 1 (LAT1). This study was conducted to investigate the biological significance of FAMT uptake in patients with esophageal cancer. From April 2008 to December 2011, 42 patients with esophageal cancer underwent both FAMT PET and FDG PET before surgical treatment. The immunohistochemical analysis of LAT1, CD98, Ki-67, CD34, p53, p-Akt and p-mTOR was performed on the primary lesions. experiments were performed to examine the mechanism of FAMT uptake using LAT1 inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). High uptake of FAMT was significantly associated with advanced stage, lymph node metastasis and the expression of LAT1, CD98, Ki-67 and CD34. LAT1 expression yielded a statistically significant correlation with CD98 expression, cell proliferation, angiogenesis and glucose metabolism. experiments revealed that FAMT was specifically transported by LAT1. The uptake of FAMT within tumor cells is determined by the LAT1 expression and correlated with cell proliferation and angiogenesis in esophageal cancer. The present experiments also confirmed the presence of LAT1 as an underlying mechanism of FAMT accumulation.
須郷 由美; 佐々木 祐二; 石岡 典子
JAEA-Review 2013-059, JAEA Takasaki Annual Report 2012, P. 17, 2014/03
The mutual separation of Am/Cm/Ln is quite difficult to establish due to their very similar chemical behavior, same oxidation state, and similar ionic radii. We have developed a new technique using the combination of the hydrophilic and lipophilic ligands dissolved in aqueous and organic phases. This technique is very useful for the mutual separation of Am/Cm/Ln, due to the multiplier effect. In this study, several kinds of hydrophilic and lipophilic derivatives of diglycolamide (DGA), dioxaoctanediamide (DOODA), and nitrilotriacetamide (NTA) were synthesized and dissolved in water or n-dodecane. These aqueous and organic solutions were irradiated with 
Co -rays. It was found that the radiolytic stabilities are not correlated with the differences in the alkyl chain length at the amidic N and in the structure of the central framework.
佐々木 一郎; 山田 圭一*; 渡辺 茂樹; 花岡 宏史*; 須郷 由美; 奥 浩之*; 石岡 典子
JAEA-Review 2013-059, JAEA Takasaki Annual Report 2012, P. 96, 2014/03
Radioisotope (RI)-labeled peptide with high affinity to receptors overexpressing on the surface of tumor cells are promising for applications in nuclear medicine such as diagnostic radiography and radiotherapy. MARSGL (H-Met-Ala-Arg-Ser-Gly-Leu-OH), a linear peptide consisting of six amino acids, has high affinity to HER2/neu receptor overexpressing in various cancer cells. Radiohalogens (radionuclides) such as radioiodine and radiobromine are versatile for clinical imaging and therapeutic applications. Thus, radiohalogenated MARSGL may have potential for clinical applications to HER2 overexpressing tumors. In this study, in order to achieve the labeling of radiohalogen for MARSGL, we design a radioiodinated peptide, F(-I)MARSGL, in which phenylalanine labeled with I (t = 8.0 d) at the position of the aromatic ring is introduced into the N-terminal of MARSGL and report a new technique to prepare radiohalogen of peptide via electrophilic destanylation.
渡辺 智; 橋本 和幸; 石岡 典子
JAEA-Review 2013-059, JAEA Takasaki Annual Report 2012, P. 97, 2014/03
As basic studies of bifunctional chelating agent for Lu -labeled antibodies, Lu complexation of DOTA and DTPA was investigated by the addition of competing metals, Ca(II), Fe(II) and Zn(II). From comparison of competing metals, the inhibition by competing metals on the Lu complexation was in the order of Ca(II)Fe(II)Zn(II) and Ca(II)Zn(II)Fe(II) as DOTA and DTPA, respectively. For comparison between DOTA and DTPA, the susceptibility to the inhibition on Lu complexation by all the three competing metals was DTPADOTA. Therefore, it was found that DTPA is advantageous for Lu complexation compared with DOTA in the presence of Ca(II), Fe(II) and Zn(II), and that the elimination of Fe from Lu solution is especially effective because the Lu complexation of DTPA is highly inhibited by Fe(II).
