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内堀 昭寛; 堂田 哲広; 青柳 光裕; 曽根原 正晃; 曽我部 丞司; 岡野 靖; 高田 孝*; 田中 正暁; 江沼 康弘; 若井 隆純; et al.
Nuclear Engineering and Design, 413, p.112492_1 - 112492_10, 2023/11
被引用回数：1 パーセンタイル：72.91(Nuclear Science & Technology)ナトリウム冷却高速炉に代表される革新炉に対し、安全性評価やそれに基づく設計最適化を自動で行うARKADIAを開発している。通常運転もしくは設計基準事象の範囲で設計最適化を行うARKADIA-Designについては、核特性-熱流動-炉心変形のマルチレベル連成解析手法等を中心技術として開発し、その基本的機能を確認した。シビアアクシデントまで含む範囲で安全性評価を行うARKADIA-Safetyの基盤技術として、炉内/炉外事象一貫解析手法の整備を進め、仮想的なシビアアクシデント事象を解析することで基本的機能を確認した。また、炉外事象に対する解析モデルの高度化、設計最適解の探索工程を合理化するAI技術の開発に着手した。
大島 宏之; 浅山 泰; 古川 智弘; 田中 正暁; 内堀 昭寛; 高田 孝; 関 暁之; 江沼 康弘
Journal of Nuclear Engineering and Radiation Science, 9(2), p.025001_1 - 025001_12, 2023/04
本論文は、安全性や経済性に関する要求、カーボンフリーエネルギー源としての要求に適合する革新的原子炉の設計を創出するためのARKADIAについて、概要及び開発計画をまとめたものである。ARKADIAは、安全設備を含めたプラント設計及び運転を最適化するための、人工知能(AI)を活用した数値解析を実現する。最先端の数値解析技術と、過去の研究開発プロジェクトで得たデータや知見を格納した知識ベースを、AIと融合させるシステムである。開発の第一フェーズでは、ナトリウム冷却高速炉を対象としてARKADIA-DesignとARKADIA-Safetyを個別に開発する。続く第二フェーズでは、既存の軽水炉に加え、コンセプト,冷却材,構造,出力の異なる多様な革新炉に適用可能な一つのシステムに統合する計画である。
内堀 昭寛; 曽我部 丞司; 岡野 靖; 高田 孝*; 堂田 哲広; 田中 正暁; 江沼 康弘; 若井 隆純; 浅山 泰; 大島 宏之
Proceedings of Technical Meeting on State-of-the-art Thermal Hydraulics of Fast Reactors (Internet), 10 Pages, 2022/09
ナトリウム冷却高速炉に代表される革新炉に対し、安全性評価やそれに基づく設計最適化を自動に行うARKADIAを開発している。通常運転もしくは設計基準事象の範囲で設計最適化を行うARKADIA-Designについては、核特性-熱流動-炉心変形の連成解析手法等を中心技術として開発し、その基本的機能を確認した。シビアアクシデントまでの範囲で安全性評価を行うARKADIA-Safetyの基盤技術として、炉内/炉外事象一貫解析手法の整備を進め、仮想的なシビアアクシデント事象を解析することで基本的機能を確認した。
大島 宏之; 森下 正樹*; 相澤 康介; 安藤 勝訓; 芦田 貴志; 近澤 佳隆; 堂田 哲広; 江沼 康弘; 江連 俊樹; 深野 義隆; et al.
Sodium-cooled Fast Reactors; JSME Series in Thermal and Nuclear Power Generation, Vol.3, 631 Pages, 2022/07
ナトリウム冷却高速炉(SFR: Sodium-cooled Fast Reactor)の歴史や、利点、課題を踏まえた安全性、設計、運用、メンテナンスなどについて解説する。AIを利用した設計手法など、SFRの実用化に向けた設計や研究開発についても述べる。
小野 綾子; 栗原 成計; 田中 正暁; 大島 宏之; 上出 英樹; 三宅 康洋*; 伊藤 真美*; 中根 茂*
Proceedings of 2017 International Congress on Advances in Nuclear Power Plants (ICAPP 2017) (CD-ROM), 10 Pages, 2017/04
ナトリウム冷却高速炉で想定されている複数種の崩壊熱除去システムの運用時における炉容器内の熱流動挙動を再現する水流動試験装置を製作した。製作した試験装置は、相似則検討および基礎試験結果により高速炉の縮尺模擬試験に適用することが示された。さらに、ループ型炉およびプール型炉で導入が検討されている浸漬型DHX運用時の炉内流動の可視化試験結果とFLUENTにより実験を数値シミュレーションした結果を示す。
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.
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.
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.
大島 康宏; 対馬 義人*
放射線と産業, (136), p.9 - 12, 2014/06
3-[
F]フルオロメチルLチロシン(L-[F]FAMT)は、癌特異性が非常に高く、L-[F]FAMT-PETによる癌の正確な診断が可能である。しかし、L-[F]FAMTには高度な腎集積・滞留が認められ、体内クリアランス遅延により生ずる癌-正常組織間のコントラスト低下によって、癌と正常組織の境界は分かりづらい。我々は癌をより明瞭に把握できるようにするため、D体アミノ酸の正常組織集積が少なく、腎臓から尿中排泄されやすい特徴に着目し、3-[F]フルオロメチルDチロシン(D-[F]FAMT)を新たに合成して、その有用性を検討した。
Ne(d,)F反応により製造したF
ガスを酢酸-酢酸カリウム溶液中に吹き込み、CHCOOFとした後、メチルDチロシンと反応させてD-[F]FAMTを合成した。担癌マウスにおける体内分布を検討した結果、D-[F]FAMTはL-[F]FAMTに比べ、正常組織集積が少なく、素早く血中から消失した。特に腎集積・滞留は、D-[F]FAMTで顕著な低下が認められた。D-[F]FAMTの癌への集積量はL-[F]FAMTに比べ低かったものの、D-[F]FAMTは正常組織に比べ、癌に十分な集積・滞留を示した。小動物用PET撮像装置によるPET撮像を行った結果、D-[F]FAMTによってL-[F]FAMTよりも癌を明瞭にイメージングすることができた。以上より、D-[F]FAMTの新規PET診断薬としての有用性が示唆された。
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.
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
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.
解良 恭一*; 須納瀬 豊*; 大島 康宏; 石岡 典子; 荒川 和久*; 小川 哲史*; 砂長 則明*; 清水 公裕*; 富永 英之*; 織内 昇*; et al.
BMC Cancer, 13, p.482_1 - 482_12, 2013/10
被引用回数：74 パーセンタイル：88.89(Oncology)The expression of L-type amino acid transporter 1 (LAT1) has been described to play essential roles in tumor growth and survival. However, it remains unclear about the clinicopathological significance of LAT1 expression in biliary tract cancer. This study was conducted to determine clinical significance of LAT1 expression and investigate whether LAT1 could be a new therapeutic target for biliary tract cancer. A total of 139 consecutive patients with resected pathologic stage I-IV biliary tract adenocarcinoma were retrospectively reviewed. Tumor sections were stained by immunohistochemistry for LAT1, CD98, Ki-67, microvessel density determined by CD34 and p53. Further, anti-tumor activity of LAT inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) was investigated using cholangiocarcinoma cell line. The expression of LAT1 was recognized in 64% of total patients, and closely correlated with CD98 expression, lymphatic metastases, cell proliferation and angiogenesis, and was a significant indicator for predicting poor outcome after surgery. Experiments showed that BCH significantly suppressed the tumor growth and BCH yielded an additive therapeutic efficacy to gemcitabine and 5-FU. A cooperative high expression of LAT1 with CD98 is a promising pathological marker to predict the outcome in biliary tract adenocarcinoma. Inhibition of LAT1 may be an effective targeted therapy for this distressing disease.
F]fluoro--methyl-D-tyrosine (D-[F]FAMT) as a novel amino acid tracer for positron emission tomography大島 康宏; 花岡 宏史*; 富永 英之*; 金井 好克*; 解良 恭一*; 山口 藍子*; 永森 收志*; 織内 昇*; 対馬 義人*; 遠藤 啓吾*; et al.
Annals of Nuclear Medicine, 27(4), p.314 - 324, 2013/05
被引用回数：15 パーセンタイル：50.05(Radiology, Nuclear Medicine & Medical Imaging)Since D-amino acid is not distributed much in the non-target organs and is rapidly excreted in the urine, radiotracer using D-amino acid would allow clear PET image of the tumor early after administration. In this study, we prepared 3-[F]fluoro--methyl-D-tyrosine (D-[F]FAMT) and evaluated its usefulness. In biodistribution studies, D-[F]FAMT showed rapid clearance from the blood, marked accumulation and retention in the tumor and low accumulation in non-target organs. The amount of D-[F]FAMT in the tumor was also lowered, tumor-to-blood ratio and tumor-to-muscle ratio of D-[F]FAMT were similar to those of correspondign L-isomer, 3-[F]fluoro--methyl-L-tyrosine (L-[F]FAMT), at every timepoint. Consequently, PET imaging with D-[F]FAMT could not show clear image of the tumor early after the administration. However, D-[F]FAMT enabled higher tumor-to-background contrast than L-[F]FAMT. In conclusions, D-[F]FAMT showed rapid blood clearance, low accumulation in non-target organs, and tumor-selective image compared with L-[F]FAMT. Thus, D-[F]FAMT could potentially serve as a novel PET tracer for imaging malignant tumors.
I]-sansalvamide A derivative渡邉 茂樹; 山田 圭一*; 津久井 匠隆*; 花岡 宏史*; 大島 康宏; 山口 藍子*; 奥 浩之*; 石岡 典子
JAEA-Review 2012-046, JAEA Takasaki Annual Report 2011, P. 88, 2013/01
Sansalvamide A (SA), a penta cyclic peptide isolated marine fungus, is a lead compound of anti-cancer reagent because the peptide has cytotoxicity against various cancer cell lines. Halogenated SA derivatives (SA-X, X = Cl, Br, I) was prepared and remarkable cytotocity against malignant human breast cancer. In this study, a radiohalogenated SA derivative [I]SA-I was prepared to conduct in vivo evaluation of SA derivatives. Synthetic scheme of [I]SA-I are as follows: an iodinated linear peptide, Boc-F(p-I)LLVL-OMe, was prepared by the conventional solid phase peptide synthesis. After preparation of stannylated peptide, Boc-F(p-SnBu)LLVL-OMe, I was labeled with electrophilic destannylation in the presence of oxidizing reagent. After deprotection of N- and C-termius, [I]SA-I was obtained successfully by macrocyclization in liquid phase. Overall labeled yield was 7%. To our best knowledge, this report is the first on the synthesis of radiolabeled SA derivative. In vivo evaluation of the SA derivative using [I]SA-I is being undertaken.
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、
Cや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Cや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、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、メチルフェニルアラニン(-Me-Phe)のパラ位にBrを導入したBr--Me-Pheを設計した。Br--Me-Pheは標識率25-40%で合成することができた。Br--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。Br--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、Br--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。
-irradiation大島 康宏; 月本 光俊*; 原田 均*; 小島 周二*
Journal of Radiation Research, 53(4), p.551 - 557, 2012/07
被引用回数：42 パーセンタイル：82.81(Biology)We have recently reported that -irradiation induces ATP release from B16 melanoma cells, which is dependent on P2X
receptor. However, the mechanism of ATP release caused by irradiation remains unclear. We here show the involvement of Cx43 in P2X receptor-dependent ATP release after 0.5 Gy -irradiation. Inhibitors of gap junction hemichannels and an inhibitory peptide for Cx43 (gap26), but not an inhibitory peptide for pannexin1 (Panx1), significantly blocked -irradiation-induced ATP release from B16 melanoma cells. We confirmed high expression of Cx43 mRNA in B16 melanoma cells. These results suggest involvement of Cx43 in the radiation-induced ATP release. We found that tyrosine phosphorylation after 0.5 Gy -irradiation was significantly blocked by P2X receptor antagonist, but not gap26, suggesting that tyrosine phosphorylation is a downstream event from P2X receptor. Since tyrosine kinase inhibitor significantly suppressed radiation-induced ATP release, tyrosine phosphorylation appears to play an important role in the Cx43-mediated ATP release downstream of P2X receptor. In conclusion, the Cx43 hemichannel, which lies downstream of P2X receptor, is involved in ATP release in response to radiation.
wild-type and mutant colorectal cancer using Cu-labeled cetuximab positron emission tomographyAchmad, A.*; 花岡 宏史*; 吉岡 弘樹*; 山元 進司*; 富永 英之*; 荒木 拓也*; 大島 康宏; 織内 昇*; 遠藤 啓吾*
Cancer Science, 103(3), p.600 - 605, 2012/03
被引用回数：25 パーセンタイル：55.86(Oncology)Overexpression of epidermal growth factor receptor (EGFR) is common in colorectal cancer. However, cetuximab, an EGFR-targeting drug, is useful only for a subset of patients and no single predictor other than V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog () mutation status has been established. In this study, we investigated cetuximab accumulation in colorectal tumors using 
In-DOTA-cetuximab, and evaluated the potential of positron emission tomography (PET) imaging of Cu-DOTA-cetuximab. We found that wild-type tumors had significantly higher In-DOTA-cetuximab accumulation than mutant tumors. Based on mutation status, a strong correlation was found between In-DOTA-cetuximab tumor uptake and EGFR expression level. Significant correlation was also found between tumor uptake of In-DOTA-cetuximab and Cu-DOTA-cetuximab. PET imaging with Cu-DOTA-cetuximab effectively visualized cetuximab accumulation in colorectal tumors with a wide variety of EGFR expression levels and different mutation status as commonly encountered in the clinical setting. Our findings suggest that this radioimmunoimaging can be clinically translated as an in vivo tool to predict cetuximab accumulation in colorectal cancer patients prior to cetuximab therapy.
