須郷 由美*; 橋本 和幸*; 川端 方子*; 佐伯 秀也*; 佐藤 俊一*; 塚田 和明; 永井 泰樹*
Journal of the Physical Society of Japan, 86(2), p.023201_1 - 023201_3, 2017/02
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
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.
佐々木 祐二; 須郷 由美; 森田 圭介; Nash, K.*; Nash, K. L.*
Solvent Extraction and Ion Exchange, 33(7), p.625 - 641, 2015/10
佐々木 祐二; 佐伯 盛久; 須郷 由美; 池田 泰久*; 川崎 武志*; 鈴木 智也*; 大橋 朗*
Solvent Extraction Research and Development, Japan, 22(1), p.37 - 45, 2015/05
新抽出剤のMIDOA(メチルイミノジオクチルアセトアミド)を用いて、Pd(II), Nb(V), Ta(V), Cr(VI), Mo(VI), W(VI), Tc(VII), Re(VII)等の溶媒抽出を行い、関連化合物のIDOA(イミノジオクチルアセトアミド)やMIDEHA(メチルイミノジエチルヘキシルアセトアミド)、TODGA(テトラオクチルジグリコールアミド)、TDGA(チアジグリコールアミド)等の結果を比較した。これらの結果より、MIDOAによる分配比はIDOAやMIDEHAよりやや高いこと、Pd, Re分配比はTODGA, TDGAより高いことを明らかにした。
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 37C 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.
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.
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
-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.
佐々木 祐二; 北辻 章浩; 須郷 由美; 津幡 靖宏; 鈴木 智也; 木村 貴海; 森田 泰治
Proceedings of 20th International Solvent Extraction Conference (ISEC 2014), p.431 - 435, 2014/09
佐々木 祐二; 津幡 靖宏; 北辻 章浩; 須郷 由美; 白数 訓子; 池田 泰久*; 川崎 武志*; 鈴木 智也*; 三村 均*; 臼田 重和*; et al.
JAEA-Research 2014-008, 220 Pages, 2014/06
文部科学省からの委託事業、原子力システム研究開発事業で行った研究「疎水性,親水性新規ジアミド化合物によるMA相互分離技術開発」3年間の成果をまとめる。本事業は次の3つのテーマからなる、(1)MA+Ln一括分離技術開発:DOODA基礎特性評価、(2)Am/Cm/Ln相互分離技術開発: Ln錯体の基礎特性評価,溶媒抽出分離法,抽出クロマトグラフィー法、(3)分離技術評価: プロセス評価。(1)では新規抽出剤であるDOODAの基礎特性の成果をまとめた。(2)では新規配位子が配位した金属錯体の構造解析結果、抽出剤を使った溶媒抽出結果、及び抽出クロマトグラフィーでのカラム分離結果をまとめた。(3)ではこれら結果を総合して相互分離フローを作成し、それぞれフラクションの元素量,放射能量,発熱量の評価を行った。
有阪 真; 渡邉 雅之; 須郷 由美; 小林 久実子*; 金尾 修*; 木村 貴海
Journal of Nuclear Science and Technology, 51(4), p.457 - 464, 2014/04
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.
須郷 由美; 佐々木 一郎; 渡辺 茂樹; 大島 康宏; 石岡 典子
Peptide Science 2013, p.355 - 358, 2014/03
HER2 is a member of the epidermal growth factor receptor family, which is overexpressed on the surface of tumor cells. H-Met-Ala-Arg-Ser-Gly-Leu-OH (MARSGL) is a linear peptide having high affinity to HER2 overexpressing in various cancer cells. In the previous study, we have synthesized a novel radioiodinated MARSGL via electrophilic destannylation in high radiochemical yield. Cu is an attractive radionuclide for positron emission tomography imaging as well as radiotherapy due to its half-life of 12.7 h and decay characteristics of both and . 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is a macrocyclic ligand for various metal ions. In this study, we designed and synthesized Cu-labeled MARSGL peptide conjugated with DOTA as an imaging probe for HER2 overexpressing tumors. In order to evaluate the usefulness of Cu-DOTA-MARSGL peptide as a PET imaging probe, studies were also performed.
佐々木 祐二; 津幡 靖宏; 北辻 章浩; 須郷 由美; 白数 訓子; 森田 泰治
Proceedings of International Nuclear Fuel Cycle Conference; Nuclear Energy at a Crossroads (GLOBAL 2013) (CD-ROM), p.1079 - 1082, 2013/09
佐々木 一郎; 山田 圭一*; 渡邉 茂樹; 花岡 宏史*; 須郷 由美; 奥 浩之*; 石岡 典子
Peptide Science 2013, p.157 - 160, 2013/03
Radioisotope (RI)-labeled peptides which have the high affinity to receptors on surface of the tumor cell are promising for diagnostic radiography (PET and SPECT) and radiotherapy. MARSGL (H-Met-Ala-Arg-Ser-Gly-Leu-OH), a linear hexapeptide consisting of six amino acids, has the high affinity to HER2/neu receptor overexpressing in various cancer cells. Thus, radiolabeled MARSGL has potential for the above mentioned purposes. Radiohalogens have various useful radionuclides, which could be introduced to aromatic compounds via tin-halogen exchange reaction. In this study, stannylated peptide Boc-F(-SnBu)MAR(Pbf)S(Bu)GL-OH was synthesized to prepare radiohalogen (Br or I)-labeled FMARSGL derivatives. First, Boc-Phe(-SnBu)-OH was prepared from Boc-Phe(-I)-OMe via Pd(0)-catalyzed coupling reaction with (BuSn) and was successfully introduced into -terminal of H-MARSGL-Trt(2-Cl) resin synthesized from H-Leu-Trt(2-Cl) resin by Fmoc-SPPS. After cleavage reaction of Boc-F(-SnBu)MAR(Pbf)S(Bu)GL-Trt(2-Cl) resin with 25% 1,1,1,3,3,3-hexafluoro-2-propanol in CHCl, Boc-F(-SnBu)MAR(Pbf)S(Bu)GL-OH was obtained and identified by using ESI-MS and NMR. Synthesis of I-labeled FMARSGL is due to report in this presentation.
須郷 由美; 田口 光正; 佐々木 祐二; 森田 泰治; 石岡 典子
JAEA-Review 2012-046, JAEA Takasaki Annual Report 2011, P. 18, 2013/01
Radiation effect on the extraction of Am was investigated using the solution of -tetraoctyldiglycolamide (TODGA) pre-irradiated with -particles and -rays. 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 both - and -rays up to 200 kGy. The absorbed dose had been estimated to be approximately 5 kGy per cycle in the actual process. Consequently, it is suggested that the extractability of TODGA for minor actinides can be maintained after recycling on the order of dozens of cycles in the process.
大島 康宏; 花岡 宏史*; 渡邉 茂樹; 須郷 由美; 渡辺 智; 富永 英之*; 織内 昇*; 遠藤 啓吾*; 石岡 典子
JAEA-Review 2011-043, JAEA Takasaki Annual Report 2010, P. 91, 2012/01
3-[F]Fluoro--methyl-L-tyrosine ([F]FAMT) is a useful amino acid tracer for PET imaging of malignant tumors. FAMT analogs labeled with Br, a positron emitter with a long half-life (t=16.1 h), could be widely used as tracers for tumor imaging. In this study, 3-[Br]bromo--methyl-L-tyrosine ([Br]BAMT) was designed, and its usefulness was evaluated as a novel PET tracer for imaging malignant tumors. In this study, both [Br]BAMT and [Br]BAMT were prepared. [Br]BAMT was stable in vitro, but was catabolized after administration in mice. Cellular accumulation and retention of [Br]BAMT using LS180 colon adenocarcinoma cells were significantly higher than those of [F]FAMT. In biodistribution studies using LS180 tumor-bearing mice, the tumor accumulation of [Br]BAMT was higher than that of [F]FAMT. However, some level of debromination was seen, and this debromination caused more retention of radioactivity in the blood and organs than was seen with [F]FAMT. PET imaging with [Br]BAMT enabled clear visualization of the tumor. In conclusion, although an improvement in stability is still needed, Br-labeled FAMT analogs could potentially serve as PET tracers for the imaging of malignant tumors.
須郷 由美; 田口 光正; 佐々木 祐二; 森田 泰治
JAEA-Review 2011-043, JAEA Takasaki Annual Report 2010, P. 18, 2012/01
Tetraoctyldiglycolamide (TODGA) has high extractability for actinides such as americium and curium from nitric acid into -dodecane. It had been obvious that the radiation chemical yield for the degradation of TODGA in -dodecane by helium ions corresponding to the alpha-particles was less than that by -rays. In this study, in order to prove an effect of linear energy transfer (LET) on the radiolysis of TODGA in -dodecane, the influence of energy of helium ions was investigated. The solution of TODGA in -dodecane was irradiated with 20-100 MeV helium ions provided by an accelerator. Incident energy of the ions on the surface of the sample was attenuated by aluminum foils. It was observed the number of molecules of TODGA decreased by the single helium ion was gradually increased with the incident energy. This result indicates that the degradation efficiency decreases with increasing LET value. Because the transient species are densely produced in the track by high LET radiations, and then decreased by recombination in the track at very early time.