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Cu -labeled trastuzumab PETPaudyal, 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 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 Cu-DOTA-trastuzumab. PET studies revealed a significantly high accumulation of Cu-DOTA-trastuzumab in the Her2/neu overexpressing NCI-H2170 tumor at 24 h and 48 h post-injection. 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.
Cu-labeled trastuzumab PETPaudyal, 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.
Cancer Science, 101(4), p.1045 - 1050, 2010/04
被引用回数：40 パーセンタイル：67.16(Oncology)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 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 Cu-DOTA-trastuzumab. PET studies revealed a significantly high accumulation of Cu-DOTA-trastuzumab in the Her2/neu overexpressing NCI-H2170 tumor at 24 h and 48 h post-injection. 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.
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：18 パーセンタイル：49.43(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*; 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 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.
Cu -labeled trastuzumab PETPaudyal, 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.
no journal, ,
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 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 Cu-DOTA-trastuzumab. PET studies revealed a significantly high accumulation of Cu-DOTA-trastuzumab in the Her2/neu overexpressing NCI-H2170 tumor at 24 h and 48 h post-injection. 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.
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.
