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論文

Medical application of radiohalogenated peptides; Synthesis and ${it in vitro}$ evaluation of F(${it p}$-$$^{131}$$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 $$^{131}$$I and $$^{211}$$At are useful for clinical imaging and therapeutic applications, and it can be introduced at the ${it para}$ position of phenylalanine residue via electrophilic destannylation. KCCYSL (Lys$$^{1}$$-Cys$$^{2}$$-Cys$$^{3}$$-Tyr$$^{4}$$-Ser$$^{5}$$-Leu$$^{6}$$) 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 ${it in vitro}$ evaluation of radiohalogenated KCCYSL derivatives. Precursor peptides, Boc-F(${it p}$-SnBu$$_{3}$$)K(Boc)C(Trt)C(Trt)Y($$^{t}$$Bu)S($$^{t}$$Bu)L-OH and Boc-F(${it p}$-SnBu$$_{3}$$)GS($$^{t}$$Bu)GK(Boc)C(Trt)C(Trt)Y($$^{t}$$Bu)S($$^{t}$$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(${it p}$-$$^{131}$$I)KCCYSL and F(${it p}$-$$^{131}$$I)GSGKCCYSL in radiochemical yield 15% and 17%, respectively. ${it In vitro}$ assays of the radioiodinated peptides for HER2 and stability in serum are being undertaken.

論文

Simultaneous analysis of silicon and boron dissolved in water by combination of electrodialytic salt removal and ion-exclusion chromatography with corona charged aerosol detection

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:7 パーセンタイル:52.67(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.

論文

Preparation and evaluation of an astatine-211-labeled sigma receptor ligand for $$alpha$$ radionuclide therapy

小川 数馬*; 水野 覚瑛*; 鷲山 幸信*; 柴 和弘*; 高橋 成人*; 小阪 孝史*; 渡辺 茂樹; 篠原 厚*; 小谷 明*

Nuclear Medicine and Biology, 42(11), p.875 - 879, 2015/11

 被引用回数:13 パーセンタイル:34.92(Radiology, Nuclear Medicine & Medical Imaging)

Sigma receptors are overexpressed in a variety of human tumors, making them potential targets for radionuclide receptor therapy. We have previously synthesized and evaluated $$^{131}$$I-labeled (+)-2-[4-(4-iodophenyl)piperidino]cyclohexanol [(+)-[$$^{131}$$I]pIV], which has a high affinity for sigma receptors. Therefore, (+)-[$$^{131}$$I]pIV significantly inhibited tumor cell proliferation in tumor-bearing mice. In the present study, we report the synthesis and the in vitro and in vivo characterization of (+)-[$$^{211}$$At]pAtV, an $$^{211}$$At-labeled sigma receptor ligand, that has potential use in $$alpha$$-radionuclide receptor therapy. The lipophilicity of (+)-[$$^{211}$$At]pAtV was similar to that of (+)-[$$^{125}$$I]-pIV. Uptake of DU-145, prostate cancer cell lines, and the biodistribution patterns in DU-145 tumor-bearing mice at 1 h post-injection were also similar between (+)-[$$^{211}$$At]pAtV and (+)-[$$^{125}$$I]-pIV. Namely, (+)-[$$^{211}$$At]pAtV demonstrated high uptake and retention in tumor via binding to sigma receptors.

論文

ワシントン大学(シアトル)留学記

渡辺 茂樹

放射線と産業, (138), p.52 - 54, 2015/06

本稿は、2013年3月から1年間アメリカ合衆国ワシントン州シアトルにあるワシントン大学へ留学中の研究成果と生活を報告したものである。

論文

Production and separation of astatine isotopes in the $$^7$$Li + $$^{nat}$$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:7 パーセンタイル:38.07(Chemistry, Analytical)

29-57MeVの$$^7$$Liビームと$$^{nat}$$Pb標的核の反応においてアスタチン同位体$$^{207-211}$$Atの生成断面積を$$alpha$$線, $$gamma$$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、$$^7$$Li + $$^{nat}$$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$$^{210}$$Atと$$^{209}$$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。

論文

Development of a widely usable amino acid tracer; $$^{76}$$Br-$$alpha$$-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:12 パーセンタイル:34.92(Radiology, Nuclear Medicine & Medical Imaging)

Radiolabeled amino acids are superior PET tracers for imaging of malignant tumors, and amino acids labeled with $$^{76}$$Br, an attractive positron emitter due to its relatively long half-life (t$$_{1/2}$$=16.2 h), could potentially be widely usable tumor imaging tracer. In this study, in consideration of stability and tumor specificity, 2-$$^{76}$$Br-bromo-$$alpha$$-methyl-L-phenylalanine (2-$$^{76}$$Br-BAMP) and 4-$$^{76}$$Br-bromo-$$alpha$$-methyl-L-phenylalanine (4-$$^{76}$$Br-BAMP) were designed and their potential as a tumor imaging agent was evaluated. No-carrier-added $$^{76}$$Br and $$^{77}$$Br, the latter of which is suitable radiobromine for basic studies due to its longer half-life (t$$_{1/2}$$ = 57.1 h), were produced. Both $$^{77}$$Br-BAMPs were stable in the plasma and in the murine body. In biodistribution studies, 2-$$^{77}$$Br-BAMP showed more rapid blood clearance and lower renal accumulation than did 4-$$^{77}$$Br-BAMP. More than 90% of injected radioactivity was excreted in the urine by 6 h post-injection of 2-$$^{77}$$Br-BAMP. High tumor accumulation of 2-$$^{77}$$Br-BAMP was observed in tumor-bearing mice and PET imaging with 2-$$^{76}$$Br-BAMP enabled clear visualization of the tumor. These findings suggest that 2-$$^{76}$$Br-BAMP would constitute a potential new PET tracer for tumor imaging and may eventually enable the wider use of amino acid tracers.

論文

Synthesis and ${{it in vitro}}$ evaluation of $$^{64}$$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 ($$^{64}$$Cu) is a useful radionuclide in nuclear medicine, and can be produced by the cyclotron. In this study, we designed and synthesized $$^{64}$$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 $$^{64}$$Cu-DOTA-MARSGL was determined by TLC and HPLC compared with a non-radioactive preparation. It was confirmed that $$^{64}$$Cu-DOTA-MARSGL was obtained in high radiochemical yield more than 94%. We also examined a stability of $$^{64}$$Cu-DOTA-MARSGL ${it in vitro}$. The chromatogram was not changed after incubation in physiological saline at 37$$^{circ}$$C overnight. In order to evaluate the usefulness as a PET imaging probe, further ${it in vitro}$ studies on the stability in human or mice plasma and the cellular uptake are in progress.

論文

Exploring of peptides with affinity to HER2 from random peptide libraries using radioisotope; Random hexapeptide libraries with fixed amino acid sequence at 1 and 2 positions

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-$$^{131}$$I)) to $$N$$-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-$$^{131}$$I)X$$^{1}$$X$$^{2}$$X$$^{3}$$X$$^{4}$$X$$^{5}$$X$$^{6}$$. Non-radioactive random peptide libraries, yXXXXXX, were prepared by Fmoc-SPPS with an automatic peptide synthesizer. Radioiodinated y(3-$$^{131}$$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.

論文

Production of highly purified no-carrier-added $$^{177}$$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:6 パーセンタイル:38.07(Chemistry, Analytical)

No-carrier-added $$^{177}$$Lu produced via the $$^{176}$$Yb(n, $$gamma$$) $$^{177}$$Yb $$rightarrow$$$$^{177}$$Lu process was separated from the macroscopic amounts of the Yb target using reversed-phase ion-pair liquid chromatography. To produce a highly purified $$^{177}$$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 $$^{177}$$Lu -labeled antibody increased from less than 5% to 88%.

論文

Synthesis of radiohalogen-labeled peptide with high affinity to HER2/neu receptor

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$$^{1}$$-Ala$$^{2}$$-Arg$$^{3}$$-Ser$$^{4}$$-Gly$$^{5}$$-Leu$$^{6}$$-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(${it p}$-$$^{131}$$I)MARSGL, in which phenylalanine labeled with $$^{131}$$I (t$$_{1/2}$$ = 8.0 d) at the ${it para}$ 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.

論文

Synthesis and ${it in vitro}$ Evaluation of $$^{64}$$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

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. $$^{64}$$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 $$beta$$$$^{+}$$ and $$beta$$$$^{-}$$. 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 $$^{64}$$Cu-labeled MARSGL peptide conjugated with DOTA as an imaging probe for HER2 overexpressing tumors. In order to evaluate the usefulness of $$^{64}$$Cu-DOTA-MARSGL peptide as a PET imaging probe,${it in vitro}$ studies were also performed.

論文

Evaluation of a wet chemistry method for isolation of cyclotron produced [$$^{211}$$At] astatine

Balkin, E. R.*; Hamlin, D. K.*; Gagnon, K.*; Chyan, M.-K.*; Pal, S.*; 渡辺 茂樹; Wilbur, D. S.*

Applied Sciences (Internet), 3(3), p.636 - 655, 2013/09

 被引用回数:20 パーセンタイル:17.25(Chemistry, Multidisciplinary)

A "wet chemistry" approach for isolation of $$^{211}$$At from an irradiated bismuth target is described. The approach involves five steps: (1) dissolution of bismuth target in conc. HNO$$_{3}$$; (2) removal of the HNO$$_{3}$$ by distillation; (3) dissolution of residue in 8 M HCl; (4) extraction of $$^{211}$$At from 8 M HCl into DIPE; and (5) extraction of $$^{211}$$At from DIPE into NaOH. Results from 55 "optimized" At isolation runs gave recovery yields of approximately 78% after decay and attenuation corrections. An attenuation-corrected average of 26$$pm$$3 mCi in the target provided isolated (actual) yields of 16$$pm$$3 mCi of $$^{211}$$At. A sixth step, used for purification of $$^{211}$$At from trace metals, was evaluated in seven runs. In those runs, isolated $$^{211}$$At was distilled under reductive conditions to provide an average 71$$pm$$8% recovery. RadioHPLC analyses of the isolated $$^{211}$$At solutions, both initial and after distillation, were obtained to examine the $$^{211}$$At species present. The primary species of $$^{211}$$At present was astatide, but astatate and unidentified species were also observed. Studies to determine the effect of bismuth attenuation on $$^{211}$$At were conducted to estimate and attenuation factor ($$sim$$1.33) for adjustment of $$^{211}$$At readings in the bismuth target.

論文

Three-dimensional and multienergy $$gamma$$-ray simultaneous imaging by using a Si/CdTe Compton camera

鈴木 義行*; 山口 充孝; 小高 裕和*; 島田 博文*; 吉田 由香里*; 鳥飼 幸太*; 佐藤 隆博; 荒川 和夫*; 河地 有木; 渡辺 茂樹; et al.

Radiology, 267(3), p.941 - 947, 2013/06

 被引用回数:10 パーセンタイル:53.1(Radiology, Nuclear Medicine & Medical Imaging)

Capabillity tests of 3D imaging for medical applications were performed by using a new Compton camera. $$^{18}$$F, $$^{131}$$I and $$^{67}$$Ga separately compacted into micro tubes were injected subcutaneously into a Wister rat and imaged after sacrifice of the rat (ex-vivo model). In a separate experiment $$^{111}$$In-chloride and $$^{131}$$I-Methylnorcholestenol were injected into a rat intravenously and $$^{64}$$Cu was injected into the stomach orally just before imaging (more physiological model). The Compton camera demonstrated its 3D multinuclear imaging capability by separating out the three nuclear distributions clearly in ex-vivo model. In the more physiological model, the distributions of $$^{131}$$I and $$^{64}$$Cu were clearly imaged although $$^{111}$$In was difficult to visualize due to blurring at low energy region of $$gamma$$-ray. In conclusion, our new Compton camera successfully demonstrated highly resolved multiplanar and multinuclear $$gamma$$-ray simultaneous imaging.

論文

Development of a $$^{76}$$Br-labeled amino acid derivative for PET imaging of tumor

花岡 宏史*; 渡邉 茂樹; 富永 英之*; 大島 康宏; 渡辺 智; 山田 圭一*; 飯田 靖彦*; 石岡 典子; 遠藤 啓吾*

JAEA-Review 2012-046, JAEA Takasaki Annual Report 2011, P. 89, 2013/01

近年、がんに対する特異性が高いPET薬剤として、$$^{11}$$Cや$$^{18}$$Fで標識したアミノ酸誘導体が開発され、臨床応用されるようになってきた。しかしながら$$^{11}$$Cや$$^{18}$$Fは半減期が非常に短いため、それぞれの病院で製造・合成する必要があり、限られた施設でしか使えないのが現状である。一方、$$^{76}$$Brは、半減期が16.1時間とポジトロン放出核種としては比較的長く、またハロゲン核種であるため母体化合物との結合にキレート剤等が必要ないことから、アミノ酸のような低分子化合物に対しても応用可能である。そこで本研究では、広く臨床使用することが可能な、新規がん診断用PETイメージング薬剤として$$^{76}$$Br標識アミノ酸誘導体の開発を計画した。基礎検討には半減期が長い放射性臭素である$$^{77}$$Br(半減期57時間)を用いて行うこととした。Br標識アミノ酸としては、$$alpha$$メチルフェニルアラニン($$alpha$$-Me-Phe)のパラ位にBrを導入したBr-$$alpha$$-Me-Pheを設計した。$$^{77}$$Br-$$alpha$$-Me-Pheは標識率25-40%で合成することができた。$$^{77}$$Br-$$alpha$$-Me-Pheを担癌マウスに投与したところ、腫瘍への高い集積性を示し、投与3時間後の腫瘍対血液比は3.94、腫瘍対筋肉比は3.95であった。$$^{76}$$Br-$$alpha$$-Me-Pheを担癌マウスに投与してPET撮像を行ったところ、腫瘍を明瞭に描出することができた。以上の結果から、$$^{76}$$Br-$$alpha$$-Me-Pheの新規がんイメージング薬剤としての有用性が示唆された。

論文

Preparation and biological evaluation of 3-[$$^{76}$$Br]bromo-$$alpha$$-methyl-L-tyrosine, a novel tyrosine analog for PET imaging of tumors

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-[$$^{18}$$F]Fluoro-$$alpha$$-methyl-L-tyrosine ([$$^{18}$$F]FAMT) is a useful amino acid tracer for PET imaging of malignant tumors. FAMT analogs labeled with $$^{76}$$Br, a positron emitter with a long half-life (t$$_{1/2}$$=16.1 h), could be widely used as tracers for tumor imaging. In this study, 3-[$$^{76}$$Br]bromo-$$alpha$$-methyl-L-tyrosine ([$$^{76}$$Br]BAMT) was designed, and its usefulness was evaluated as a novel PET tracer for imaging malignant tumors. In this study, both [$$^{76}$$Br]BAMT and [$$^{77}$$Br]BAMT were prepared. [$$^{77}$$Br]BAMT was stable in vitro, but was catabolized after administration in mice. Cellular accumulation and retention of [$$^{77}$$Br]BAMT using LS180 colon adenocarcinoma cells were significantly higher than those of [$$^{18}$$F]FAMT. In biodistribution studies using LS180 tumor-bearing mice, the tumor accumulation of [$$^{77}$$Br]BAMT was higher than that of [$$^{18}$$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 [$$^{18}$$F]FAMT. PET imaging with [$$^{76}$$Br]BAMT enabled clear visualization of the tumor. In conclusion, although an improvement in stability is still needed, $$^{76}$$Br-labeled FAMT analogs could potentially serve as PET tracers for the imaging of malignant tumors.

論文

Production of radioactive bromine $$^{76}$$Br

渡辺 智; 渡邉 茂樹; 飯田 靖彦*; 花岡 宏史*; 遠藤 啓吾*; 石岡 典子

JAEA-Review 2011-043, JAEA Takasaki Annual Report 2010, P. 92, 2012/01

現在PET診断に用いられている核種は半減期が2時間以下と非常に短いため、抗体のような集積に時間のかかる化合物を利用したPET診断には限界がある。これを解決するために、本研究では新規ポジトロン放出核種として半減期が16.2時間の$$^{76}$$Brの製造法の開発を行った。セレン化銅をターゲットとし、$$^{76}$$Se(p,n) $$^{76}$$Br反応を用い、原子力機構のTIARA-AVFサイクロトロンからの20MeV, H$$^{+}$$ビームで照射をして$$^{76}$$Brを生成した。$$^{76}$$Brの回収にはターゲット由来の毒物であるSeの混入を防ぐために乾式蒸留法を採用し、Brトラップ回収条件等の検討により、$$^{76}$$Brの高純度分離を達成した。分離条件については、回収方法及び電気炉内温度の最適化により、ターゲット中に生成した全$$^{76}$$Brの放出及びテフロンチューブ内でのロスの低減により、30%程度の回収率を約80%にまで向上させることに成功した。

論文

Conceptual design study of JSFR, 2; Reactor system

衛藤 将生*; 神島 吉郎*; 岡村 茂樹*; 渡辺 収*; 大山 一弘*; 根岸 和生; 小竹 庄司*; 阪本 善彦; 上出 英樹

Proceedings of International Conference on Fast Reactors and Related Fuel Cycles (FR 2009) (CD-ROM), 10 Pages, 2012/00

JSFRの設計においては、建設費の低減を目指して、原子炉容器径を小さく、炉内構造物を簡素にしている。原子炉容器径の低減は、先進的な燃料交換システムと運転中高温になる原子炉容器の概念を採用することで達成している。しかし、原子炉容器径の低減により、上部プレナム内の流速が増加し、流動場が厳しくなる。このため、カバーガスの巻き込みとホットレグ吸込口における液中渦によるキャビテーションの発生を抑制するため、上部プレナム流動場の最適化を実施した。加えて、設計地震荷重が増大し、かつ原子炉容器壁が上部プレナムの熱過渡に直接曝されることから、地震荷重と熱荷重に対する構造健全性を評価した。本論文は、これら原子炉構造の設計研究の特徴と結果について記載するものである。

論文

Preparation and biological evaluation of 3-[$$^{76}$$Br]bromo-$$alpha$$-methyl-L-tyrosine, a novel tyrosine analog for positron emission tomography imaging of tumors

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

Nuclear Medicine and Biology, 38(6), p.857 - 865, 2011/08

 被引用回数:8 パーセンタイル:61.92(Radiology, Nuclear Medicine & Medical Imaging)

3-[$$^{18}$$F]fluoro-$$alpha$$-methyl-L-tyrosine ([$$^{18}$$F]FAMT) is a useful amino acid tracer for positron emission tomography (PET) imaging of malignant tumors. FAMT analogs labeled with $$^{76}$$Br, a positron emitter with a long half-life ($$t$$$$_{1/2}$$=16.1 h), could be widely used as tracers for tumor imaging. In this study, 3-[$$^{76}$$Br]bromo-$$alpha$$-methyl-L-tyrosine ([$$^{76}$$Br]BAMT) was designed, and its usefulness was evaluated as a novel PET tracer for imaging malignant tumors. In this study, both [$$^{76}$$Br]BAMT and [$$^{77}$$Br]BAMT were prepared. [$$^{77}$$Br]BAMT was stable in vitro, but was catabolized after administration in mice. Cellular accumulation and retention of [$$^{77}$$Br]BAMT using LS180 colon adenocarcinoma cells were significantly higher than those of [$$^{18}$$F]FAMT. In biodistribution studies using LS180 tumor-bearing mice, the tumor accumulation of [$$^{77}$$Br]BAMT was higher than that of [$$^{18}$$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 [$$^{18}$$F]FAMT. PET imaging with [$$^{76}$$Br]BAMT enabled clear visualization of the tumor. In conclusion, although an improvement in stability is still needed, $$^{76}$$Br-labeled FAMT analogs could potentially serve as PET tracers for the imaging of malignant tumors.

論文

Imaging and biodistribution of Her2/neu expression in non-small cell lung cancer xenografts with $$^{64}$$Cu -labeled trastuzumab PET

Paudyal, P.*; Paudyal, B.*; 花岡 宏史*; 織内 昇*; 飯田 靖彦*; 吉岡 弘樹*; 富永 英之*; 渡辺 智; 渡邉 茂樹; 石岡 典子; et al.

JAEA-Review 2010-065, JAEA Takasaki Annual Report 2009, P. 108, 2011/01

Non-small cell lung carcinomas (NSCLC) overexpress the Her2/neu gene in approximately 59% of cases. Trastuzumab, a humanized monoclonal antibody, interferes with Her2 signaling and is approved for the treatment of Her2/neu overexpressing breast cancer. However, its therapeutic use in Her2/neu overexpressing NSCLC remains obscure. The present study aimed to determine the role of $$^{64}$$Cu-labeled trastuzumab positron emission tomography (PET) for non-invasive imaging of Her2/neu expression in NSCLC. Imaging of Her2/neu expression was performed in NCI-H2170 tumor-bearing mice with $$^{64}$$Cu-DOTA-trastuzumab. PET studies revealed a significantly high accumulation of $$^{64}$$Cu-DOTA-trastuzumab in the Her2/neu overexpressing NCI-H2170 tumor at 24 h and 48 h post-injection. $$^{64}$$Cu-DOTA-trastuzumab showed a very clear image of a Her2/neu positive tumor and appeared to be effective as a PET tracer for imaging of Her2/neu gene expression in NSCLC, suggesting its potential clinical use for identifying patients that might benefit from trastuzumab-based therapy.

論文

PET studies of neuroendcrine tumors by using $$^{76}$$Br-$$m$$-bromobenzylguanidine ($$^{76}$$Br-MBBG)

渡邉 茂樹; 花岡 宏史*; Liang, J. X.*; 飯田 靖彦*; 渡辺 智; 遠藤 啓吾*; 石岡 典子

JAEA-Review 2010-065, JAEA Takasaki Annual Report 2009, P. 107, 2011/01

$$^{131}$$I-$$m$$-Iodobenzylgunanidine ($$^{131}$$I-MIBG), functional analogue of norepinephrine, has been employed for the therapy of neuroendcrine tumors which express norepinephrine transporter (NET). $$^{123}$$I-MIBG scintigraphy has been also used for diagnosis of NET positive tumors such as detecting metastasis, investigating suitability and monitoring response to the treatment with $$^{131}$$I-MIBG. However, $$^{123}$$I-MIBG scintigraphy has limitation to diagnose small legions due to its lower sensitivity and spatial resolution. Since positron emission tomography (PET) is superior to scintigraphy, positron emitter labeled MIBG has potential to improve diagnostic ability of NET positive neuroendcrine tumors. Then, we have reveal the utility of positron emitter $$^{76}$$Br labeled m-bromobenzylguanidine ($$^{76}$$Br-MBBG) as a PET tracer for NET positive tumor.

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