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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

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.

Cancer Science, 101(4), p.1045 - 1050, 2010/04

 被引用回数:34 パーセンタイル:67.02(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 $$^{64}$$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

Production of radioisotopes for nuclear medicine using ion-beam technology and its utilization for both therapeutic and diagnostic application in cancer

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 $$^{177}$$Lu-DOTA-NuB2 using carrier-free $$^{177}$$Lu, and obtained remarkable results for decreasing tumor. Tumor specific radionuclide therapy using $$^{177}$$Lu is effective therapy with less adverse reactions.

論文

Evaluation of $$^{64}$$Cu-labeled DOTA-$$_{rm D}$$-Phe$$^{1}$$-Tyr$$^{3}$$-octreotide ($$^{64}$$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:49.88(Radiology, Nuclear Medicine & Medical Imaging)

In-111 ($$^{111}$$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 $$^{64}$$Cu-labeled octreotide analog, $$^{64}$$Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-$$_{rm D}$$-Phe$$^{1}$$-Tyr$$^{3}$$-octreotide ($$^{64}$$Cu-DOTA-TOC). $$^{64}$$Cu-DOTA-TOC can be produced in amounts efficient for clinical study with high radiochemical yield. $$^{64}$$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 $$^{64}$$Cu was higher than that of $$^{111}$$In in all organs except kidney. In tumor-bearing mice, $$^{64}$$Cu-DOTA-TOC showed a high accumulation in the tumors, and the tumor-to-blood ratio reached as high as 8.81 $$pm$$ 1.17 at 6 h after administration. $$^{64}$$Cu-DOTA-TOC showed significantly higher accumulation in the tumor than $$^{64}$$Cu-TETA-OC and $$^{64}$$Cu-DOTA-OC. PET showed a very clear image of the tumor, which was comparable to that of $$^{18}$$F-FDG PET and very similar to that of $$^{64}$$Cu-TETA-OC. $$^{64}$$Cu-DOTA-TOC clearly imaged a somatostatin receptor-positive tumor and seemed to be a potential PET tracer in the clinical phase.

論文

イオンビームによる医学用放射性核種の製造と腫瘍特異的な癌診断と治療への応用

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.

口頭

がん診断・治療における新規放射性核種の有用性

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$$^{18}$$F標識グルコース($$^{18}$$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、$$^{64}$$Cu, $$^{67}$$Cu, $$^{76}$$Br, $$^{177}$$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。

口頭

PET imaging and biodistribution of $$^{64}$$Cu labeled monoclonal antibody

Paudyal, 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 $$^{64}$$Cu labeled antibody was investigated by animal study. Anti CD20 antibody, NuB2 was conjugated with the chelator, DOTA and radiolabeled with $$^{64}$$Cu. For animal study, nude mice bearing lymphoma (Raji tumor) were injected with $$^{64}$$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 $$^{64}$$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 $$^{64}$$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.

口頭

Imaging and localization of $$^{64}$$Cu labeled trastuzumab in Her2/neu overexpressing non-small cell lung cancer xenografts

Paudyal, 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 $$^{64}$$Cu labeled trastuzumab using in vivo PET imaging. Imaging of Her2/neu expression was performed with $$^{64}$$Cu -DOTA- trastuzumab in H2170 tumor bearing mouse with PET. PET studies revealed relatively high accumulation of $$^{64}$$Cu -DOTA- trastuzumab in the Her2/neu overexpressing H2170 tumor at 48 h post injection. The success of $$^{64}$$Cu -DOTA- trastuzumab brought an insight to PET imaging of Her2/neu gene expression in NSCLC patients with $$^{64}$$Cu -DOTA- trastuzumab to define the patients who might be benefited with trastuzumab based therapy.

口頭

A Direct comparison between in vivo optical imaging and PET imaging in mice

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 $$^{64}$$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.

口頭

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.

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 $$^{64}$$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.

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