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Dinh, T.-H.*; 鈴木 悠平*; 荒居 剛己*; Li, B.*; Dunne, P.*; O'Sullivan, G.*; 藤岡 慎介*; 長谷川 登; 河内 哲哉; 錦野 将元; et al.
Applied Physics Letters, 107(12), p.121101_1 - 121101_5, 2015/09
被引用回数：5 パーセンタイル：25.06(Physics, Applied)We have characterized the spectral structure and the temporal history of the laser-produced high-Z multi-charged ion plasmas for the efficient water window soft X-ray sources. Strong unresolved transition array (UTA) emission was observed due to 4d-4f and 4f-5g transitions from Au, Pb, and Bi plasmas in the 280-700 eV photon energy region. The temporal behavior of the emission was essentially similar of that of the laser pulse with a slight delay between different transitions. These results provide feedback for accurate modeling of the atomic processes with the radiative hydrodynamic simulations.
-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：21 パーセンタイル：59.06(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.
飯田 靖彦*; 花岡 宏史*; 渡辺 智; 渡邉 茂樹; 石岡 典子; 吉岡 弘樹*; 山元 進司*; Paudyal, P.*; Paudyal, B.*; 樋口 哲也*; et al.
JAEA-Review 2009-041, JAEA Takasaki Annual Report 2008, P. 108, 2009/12
As antibody binds specifically to corresponding antigens, radiolabeled antibody also binds to cells expressing antigens on surface membranes. Large amounts of antibodies labeled with cytotoxic radionuclides are administered intravenously in cancer patients, after diagnostic imaging using the tracer amount of radiolabeled antibody. In this study, we developed this therapy, called radioimmunotherapy, for effective treatment in cancer patients without damaging normal cells which do not express antigens. We developed 
Lu-DOTA-NuB2 using carrier-free Lu, and obtained remarkable results for decreasing tumor. Tumor specific radionuclide therapy using Lu is effective therapy with less adverse reactions.
Cu-labeled DOTA-
-Phe
-Tyr
-octreotide (Cu-DOTA-TOC) for imaging somatostatin receptor-expressing tumors花岡 宏史*; 富永 英之*; 山田 圭一*; Paudyal, P.*; 飯田 靖彦*; 渡邉 茂樹; Paudyal, B.*; 樋口 徹也*; 織内 昇*; 遠藤 啓吾*
Annals of Nuclear Medicine, 23(6), p.559 - 567, 2009/08
被引用回数：16 パーセンタイル：48.11(Radiology, Nuclear Medicine & Medical Imaging)In-111 (
In)-labeled octreotide has been clinically used for imaging somatostatin receptor-positive tumors, and radiolabeled octreotide analogs for positron emission tomography (PET) have been developed. The aim of this study is to produce and fundamentally examine a Cu-labeled octreotide analog, Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid--Phe-Tyr-octreotide (Cu-DOTA-TOC). Cu-DOTA-TOC can be produced in amounts efficient for clinical study with high radiochemical yield. Cu-DOTA-TOC was stable in vitro, but time-dependent transchelation to protein was observed after injection into mice. In biodistribution studies, the radioactivity of Cu was higher than that of In in all organs except kidney. In tumor-bearing mice, Cu-DOTA-TOC showed a high accumulation in the tumors, and the tumor-to-blood ratio reached as high as 8.81 
1.17 at 6 h after administration. Cu-DOTA-TOC showed significantly higher accumulation in the tumor than Cu-TETA-OC and Cu-DOTA-OC. PET showed a very clear image of the tumor, which was comparable to that of 
F-FDG PET and very similar to that of Cu-TETA-OC. Cu-DOTA-TOC clearly imaged a somatostatin receptor-positive tumor and seemed to be a potential PET tracer in the clinical phase.
飯田 靖彦*; 花岡 宏史*; Paudyal, P.*; Paudyal, B.*; 渡辺 智; 石岡 典子; 渡邉 茂樹; 松橋 信平; 吉岡 弘樹*; 樋口 徹也*; et al.
JAEA-Review 2008-055, JAEA Takasaki Annual Report 2007, P. 114, 2008/11
Optical imaging is recently developed for in vivo molecular imaging. It requires only a simple system, and has advantage of relatively low cost. Furthermore, optical imaging probes can provide the highest signal-to-noise ratio for molecular targeting, so optical imaging is ideal candidate for molecular imaging. In this study, we prepared a probe, which labeled with both radioisotope and fluorescent dye, and evaluated the difference of images from PET and optical imaging, and compare the characteristics of both imaging methods. From our results, multimodal imaging system can provide complementary information about the functional status of various tissues, and can improve the accuracy of tumor diagnosis.
飯田 靖彦*; 花岡 宏史*; 片渕 竜也*; 渡邉 茂樹; 石岡 典子; 渡辺 智; 松橋 信平; 樋口 徹也*; 織内 昇*; 遠藤 啓吾*
JAEA-Review 2007-060, JAEA Takasaki Annual Report 2006, P. 128, 2008/03
PET is superior in quantitative measurement, so F-FDG-PET is most valuable tool for tumor diagnosis. Although several positron emitters have been used for PET, their uses are limited for their short half-lives. Compared with these radionuclides, Cu and 
Br have appropriate properties (Br: T
= 16.1hr, Cu: T = 12.7hr) and they may have great potentials for PET utility. In this study, we synthesized monoclonal antibody (mAb) labeled with Cu or Br and evaluated their potential for tumor diagnosis with PET. The results of tumor localization studies show that Cu or Br labeled mAb were highly accumulated to tumor. From these data, the use of Cu and Br has great advantage for PET utility.
島田 賢也*; 東口 光晴*; 有田 将司*; 生天目 博文*; 谷口 雅樹*; 藤森 伸一; 斎藤 祐児; 藤森 淳; 高田 恭孝*; Shin, S.*; et al.
Journal of Magnetism and Magnetic Materials, 310(2, Part1), p.e57 - e58, 2007/03
近藤半導体CeRhAs及び半金属CeRhSbの電子状態を、40-5948eVの放射光を利用した光電子分光により調べた。光励起断面積のエネルギー依存性に基づき、これらの物質のp-d-f状態を明らかにした。
飯田 靖彦*; 花岡 宏史*; 片渕 竜也*; 渡辺 智; 石岡 典子; 松橋 信平; 織内 昇*; 樋口 徹也*; 宮久保 満之*; 遠藤 啓吾*
JAEA-Review 2006-042, JAEA Takasaki Annual Report 2005, P. 165, 2007/02
Radioimmunotherapy (RIT) becomes one of the most promising treatments for cancer therapy. Recently, because various radioisotopes are being used for RIT, the efficient tailor-made therapy is thought to be possible. The high energy 
-particle-emitter, such as 
Y (2.28 MeV), seems particularly well suited for the treatment of relatively large tumor masses, but the middle energy -particles, such as 
Cu (0.18-0.58 MeV), may have an advantage in treating small lesions. In this study, we prepared Cu and evaluated its potential of application for RIT in tumor bearing mice. Our results of tumor localization studies show that Cu was expected to be suitable for RIT.
La
RhAs; A Collapse of the energy gap in the Kondo semiconductor島田 賢也*; 東口 光晴*; 藤森 伸一; 斎藤 祐児; 藤森 淳; 生天目 博文*; 谷口 雅樹*; 笹川 哲也*; 高畠 敏郎*
Physica B; Condensed Matter, 383(1), p.140 - 141, 2006/08
被引用回数：1 パーセンタイル：6.81(Physics, Condensed Matter)近藤半導体CeRhAsのLa置換によるエネルギーギャップの崩壊を解明するため、CeLaRhAs(0
x0.05)単結晶の高分解能角度分解光電子分光を行った。xの増加とともにフェルミエネルギー近傍のCe4f状態が減少し、高結合エネルギーに4f由来の構造が現れた。一方、Rh 4dに由来する状態は、置換によってあまり変化しない。新たに現れたCe 4f状態はインコヒーレントな性質であり、x
0.02における半導体状態の崩壊の原因である。
(T=Rh, Ir, and Co); Band-calculation and tight-binding approach眞榮平 孝裕; 瀧本 哲也; 堀田 貴嗣; 上田 和夫*; 樋口 雅彦*; 長谷川 彰*
Journal of the Physical Society of Japan, Vol.71, Supplement, p.285 - 287, 2002/00
被引用回数：8 パーセンタイル：50.46(Physics, Multidisciplinary)最近、重い電子系物質群に属し超伝導を示す化合物CeTIn(T=Rh, Ir and Co)が発見された。一方、大貫グループ(阪大院理)らにより、CeIrIn,CeCoInの純良な単結晶育成が行われ、明瞭なde Haas van Alphen(dHvA)ブランチが観測されている。観測されたdHvAブランチは円柱形状の2次元的フェルミ面によってよく説明される。さて、CeIrIn及びCeCoGaのようないわゆるCe-115系の電子構造を理解するために、次のような2段階の解析をおこなう。第一段階は、相対論的線形化Augmented Plane Wave法を用いたバンド計算によりフェルミ面を決定する。そして得られたフェルミ面のうち、特にdHvA角度依存の実験によって観測されている2次元的フェルミ面に着目して詳細な解析をする。第二段階は、フェルミレベル近傍のエネルギーバンド構造を、簡単化された強束縛模型を用いて解析をする。最近接Ce イオン間の f電子のホッピングの大きさや結晶場パラメーターは、第一段階のバンド計算において得られたフェルミ面を再現するように決定される。さらにクーロン相互作用をこの強束縛模型に加えることにより、Ce化合物に対する簡単化されたHamiltonianを導出すし、4
電子系における磁性及び超伝導を微視的な観点から論じる1つの方法を提案する。
飯田 靖彦*; 花岡 宏史*; 吉岡 弘樹*; 宮久保 満之*; Paudyal, B.*; 樋口 徹也*; 織内 昇*; 遠藤 啓吾*; 片渕 竜也*; 石岡 典子; et al.
no journal, ,
近年、がん診断におけるF標識グルコース(F-FDG)の有用性が明らかとなり、多数の施設においてPETによる画像診断が行われるようになっている。しかしながら、現在PETに用いられている放射性同位元素はいずれも半減期が短く、その利用には制限があるのが現状である。そこで、製薬会社において製造し、医療現場への供給が可能な半減期を有する新規PET用核種の製造とそれを用いた放射性薬剤の開発・有効性の確認に関する研究を進めている。本シンポジウムにおいては、新規核種として開発を進めている、Cu, Cu, Br, Luについて、それぞれの核種の特徴及び研究開発の進捗を紹介する。
Br- or Cu-labeled antibody for immuno-PET in quantitative evaluation of radioimmunotherapy飯田 靖彦*; 花岡 宏史*; 石岡 典子; 片渕 竜也*; 渡辺 智; 渡邉 茂樹; 松橋 信平; 樋口 徹也*; 織内 昇*; 遠藤 啓吾*
no journal, ,
PET is superior in quantitative measurement, so F-FDG-PET is most valuable tool for tumor diagnosis. Although several positron emitters have been used for PET, their uses are limited for their short half-lives. Compared with these radionuclides, Cu and Br have appropriate properties (Br: T = 16.1 hr, Cu: T = 12.7 hr) and they may have great potentials for PET utility. In this study, we synthesized monoclonal antibody (mAb) labeled with Cu or Br and evaluated their potential for tumor diagnosis with PET. The results of tumor localization studies show that Cu or Br labeled mAb were highly accumulated to tumor. From these data, the use of Cu and Br has great advantage for PET utility.
Cu labeled monoclonal antibodyPaudyal, P.*; Paudyal, B.*; 飯田 靖彦*; 花岡 宏史*; 渡辺 智; 石岡 典子; 渡邉 茂樹; 高柳 恵美*; 吉岡 弘樹*; 織内 昇*; et al.
no journal, ,
Quantitative PET imaging using Cu labeled antibody was investigated by animal study. Anti CD20 antibody, NuB2 was conjugated with the chelator, DOTA and radiolabeled with Cu. For animal study, nude mice bearing lymphoma (Raji tumor) were injected with Cu-DOTA-NuB2. The PET imaging followed by the biodistribution studies were done at 10min, 24h and 48h post injection. PET imaging showed the significant Cu-DOTA-NuB2 accumulations in the tumor. Biodistribution studies also revealed the significant uptake in tumor than that in muscle region at any time point. This study demonstrated the utility of Cu labeled antibody as a diagnostic imaging agent for PET and the success can be translated into clinic for the quantitative targeted imaging with PET.
飯田 靖彦*; Paudyal, P.*; 吉岡 弘樹*; 富永 英之*; 花岡 宏史*; Zhang, S.*; 穂坂 正博*; 竹内 利行*; 飛田 成史*; 渡辺 智; et al.
no journal, ,
本研究では、PET及び蛍光イメージングを組合せたマルチモダリティの有用性について検討するために、分子内に、放射性核種(RI)標識部位と蛍光標識部位を有するProbeを作製し、各々の画像を直接比較することで両者から得られる情報の同一性,画像の特徴を明らかにすることを目的とした。RI及び蛍光色素で標識するprobeは、CD20を抗原とする抗体:NuB2を用い、Cu及び蛍光色素を標識したNuB2をマウスに投与し、24時間後にPET及び蛍光撮像を行った。蛍光イメージングは体表面付近しか検出できないため、PET画像とは異なる画像を得る結果となったが、皮下に移植した腫瘍の評価には有用であると考えられる。マルチモダリティは各々の長所を組合せて利用することを可能とし、有用な情報をもたらすことが期待できる。
飯田 靖彦*; 花岡 宏史*; 吉岡 弘樹*; 高柳 恵美*; 渡邉 茂樹; 石岡 典子; 渡辺 智; 松橋 信平; Paudyal, P.*; 樋口 徹也*; et al.
no journal, ,
Some new radionuclides would be useful for cancer diagnosis and therapy. Our project is to prepare these radionuclides, to apply them to many radiopharmaceuticals and to investigate usefullness of those new radiopharmaceuticals. Radio immuno therapy (RIT) is one of the most promising treatments for cancer therapy. And assessment of radiation dose to both tumor and normal tissues is very important to RIT. PET can estimate radiation dose directly, but general positron emittors don't suit for labeling of antibody because of their short half-lives. Cu and Br have appropriate properties (Cu: T = 12.7 hr, Br: T = 16.1 hr) and they may have great potentials for immuno-PET. We have synthesized Cu or Br labeled monoclonal antibody and evaluated potentials for in vivo quantitative evaluation of RIT. And we synthesized Br labeled glucose (BrDG). We evaluated its utility for tumor diagnosis. These new radiopharmaceuticals are very useful for cancer diagnosis and therapy. We will develop various radiopharmaceuticals labeled with these new radionuclides and apply them to clinical medicine in future.
Cu labeled trastuzumab in Her2/neu overexpressing non-small cell lung cancer xenograftsPaudyal, P.*; Paudyal, B.*; 飯田 靖彦*; 花岡 宏史*; 渡辺 智; 石岡 典子; 渡邉 茂樹; 高柳 恵美*; 吉岡 弘樹*; 織内 昇*; et al.
no journal, ,
Non-small cell lung carcinoma (NSCLC) overexpress Her2/neu gene in approximately 20% of the cases. Trastuzumab a humanized monoclonal antibody targets Her2/neu and inhibits neoplastic cell proliferation and significantly increases survival of patients with advanced metastatic breast cancer. The present study aimed to determine the effect of trastuzumab in Her2/neu expressing NSCLC with Cu labeled trastuzumab using in vivo PET imaging. Imaging of Her2/neu expression was performed with Cu -DOTA- trastuzumab in H2170 tumor bearing mouse with PET. PET studies revealed relatively high accumulation of Cu -DOTA- trastuzumab in the Her2/neu overexpressing H2170 tumor at 48 h post injection. The success of Cu -DOTA- trastuzumab brought an insight to PET imaging of Her2/neu gene expression in NSCLC patients with Cu -DOTA- trastuzumab to define the patients who might be benefited with trastuzumab based therapy.
Cu for immuno-PET; In vivo measurement of radiation dose for radioimmunotherapy飯田 靖彦*; 花岡 宏史*; 片渕 竜也*; 渡辺 智; 石岡 典子; 松橋 信平; 織内 昇*; 樋口 徹也*; 宮久保 満之*; 遠藤 啓吾*
no journal, ,
Radioimmunotherapy (RIT) becomes one of the most promising treatments for cancer therapy. Recently, RIT becomes available for clinical use and shows high efficacy, but it has some adverse effects for radiation to normal tissues and its therapeutic window is limited. So, assessment of radiation dose deliver to both tumor and normal tissues is very important for RIT. PET is superior in quantitative measurement and it can estimate radiation dose directly. Although representative positron emitter has short half-life, which is not good for labeling of antibody, Cu has appropriate property, T = 12.7 hr, and it may have a great potential for immuno-PET. In this study, we prepared a radioimmunoconjugate, NuB2, anti-CD20 monoclonal antibody (mAb), labeled with Cu, and evaluated potential for in vivo quantitative measurement of radiation dose for RIT. NuB2 was labeled with Cu. For in vivo studies, SCID mice bearing CD20
tumor were used. After administration, biodistribution and PET imaging were performed. For the results of biodistribution, Cu-NuB2 was highly accumulated to CD20 tumor, and PET images could show the same results. From these date, the use of Cu immuno-PET has potential for accurately measurement of radiation dose for RIT.
Cu for quantitative evaluation of radioimmunotherapy飯田 靖彦*; 花岡 宏史*; 片渕 竜也*; 渡辺 智; 石岡 典子; 松橋 信平; 織内 昇*; 樋口 徹也*; 宮久保 満之*; 遠藤 啓吾*
no journal, ,
Cu is one of the most attractive candidate emitter for radioimmunotherapy (RIT). Cu releases positron emitter (0.653 MeV, 18%) as well as middle energy -particles (0.578 MeV, 37%), so it can be applied for diagnostic imaging with PET. PET is superior in quantitative measurement and suitable for evaluation of therapeutic effect with RIT. PET can also directly estimate radiation dose of RIT. In this study, we prepared a radioimmunoconjugate, NuB2, anti-CD20 monoclonal antibody (mAb), labeled with Cu, and evaluated its potential for PET imaging with RIT. NuB2 was labeled with Cu. For in vivo studies, SCID mice bearing CD20 tumor were used. After administration, biodistribution and PET imaging were performed. For the results of biodistribution, Cu-NuB2 was highly accumulated to CD20 tumor, and PET images could show the same results. From these date, the use of Cu for PET imaging has potential for accurately evaluation of therapeutic effect of RIT.
飯田 靖彦*; 花岡 宏史*; 渡辺 智; 石岡 典子; 渡邉 茂樹; 松橋 信平; Paudyal, B.*; 織内 昇*; 樋口 徹也*; 遠藤 啓吾*
no journal, ,
Optical imaging is recently developed for in vivo molecular imaging. It requires only a simple system, and has advantage of relatively low cost. Furthermore, a probe for optical imaging can be designed to change its signal characteristic when it has interaction with the specific target. This property provides the highest signal-to-noise ratio for molecular targeting, so optical imaging is ideal candidate for molecular imaging. On the other hand, optical imaging is poor for tissue penetration and has limitation of deep tissue surveying. In this study, we prepared a probe, which labeled with both radioisotope and fluorescent dye, and evaluated the difference of images from PET and optical imaging, and compare the characteristics of both imaging methods. Anti-CD20 antibody, NuB2, was labeled with Cu and fluorescent dye. For in vivo imaging studies, tumor bearing mice were used. After administration of this probe, imaging was performed with PET and optical imaging. For the results, optical imaging could not detect deep tissue, so optical image was different from PET image. Compared with data from extracted tissue activity, optical image does not reflect the accurate tissue distribution, but it has utility for evaluation of subcutaneous transplanted tumor.
花岡 宏史*; 飯田 靖彦*; 樋口 徹也*; 織内 昇*; 遠藤 啓吾*; 渡辺 智; 渡邉 茂樹; 石岡 典子
no journal, ,
近年、治療効果の増強を目的として抗体に放射性同位元素(RI)を結合したRI標識抗体を投与しがんを治療する放射免疫療法が注目されている。線放出核種であるイットリウム-90で標識した抗CD20抗体(ゼヴァリン)は、悪性リンパ腫の治療薬として日本でも認可されており、新規治療薬として高い治療効果を示している。その一方で、放射免疫療法では十分な治療効果が得られていない場合も多く存在することから、治療成績の向上のためにさまざまな方策が考えられている。その一つとして、新規RIを用いた放射免疫療法が検討されている。抗体が腫瘍へ集積するまでには数日を要することから、6.7日と比較的長い半減期を有するルテチウム-177(Lu)が新規核種として期待されている。そこで本研究では、Lu標識抗体を用いた効果的な放射免疫療法を目指して、Lu標識抗体に関する基礎的検討を行った。
Yb(n, 
) Yb
Lu反応で製造したLuを用いてLu標識抗体による胆癌マウスを用いた治療実験を行った結果、投与早期より腫瘍が縮小し、6日後には腫瘍が消失したことから、Lu標識抗体の放射免疫療法薬剤としての有用性が示された。
