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論文

Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer

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:51 パーセンタイル:5.71(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.

論文

Biological significance of fluorine-18-$$alpha$$-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:14 パーセンタイル:36.78(Oncology)

Fluorine-18-$$alpha$$-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. ${it In vitro}$ 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. ${it In vitro}$ 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.

論文

Clinical significance of L-type amino acid transporter 1 expression as a prognostic marker and potential of new targeting therapy in biliary tract cancer

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:31 パーセンタイル:18.23(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.

論文

Biological evaluation of 3-[$$^{18}$$F]fluoro-$$alpha$$-methyl-D-tyrosine (D-[$$^{18}$$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:7 パーセンタイル:58.57(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-[$$^{18}$$F]fluoro-$$alpha$$-methyl-D-tyrosine (D-[$$^{18}$$F]FAMT) and evaluated its usefulness. In biodistribution studies, D-[$$^{18}$$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-[$$^{18}$$F]FAMT in the tumor was also lowered, tumor-to-blood ratio and tumor-to-muscle ratio of D-[$$^{18}$$F]FAMT were similar to those of correspondign L-isomer, 3-[$$^{18}$$F]fluoro-$$alpha$$-methyl-L-tyrosine (L-[$$^{18}$$F]FAMT), at every timepoint. Consequently, PET imaging with D-[$$^{18}$$F]FAMT could not show clear image of the tumor early after the administration. However, D-[$$^{18}$$F]FAMT enabled higher tumor-to-background contrast than L-[$$^{18}$$F]FAMT. In conclusions, D-[$$^{18}$$F]FAMT showed rapid blood clearance, low accumulation in non-target organs, and tumor-selective image compared with L-[$$^{18}$$F]FAMT. Thus, D-[$$^{18}$$F]FAMT could potentially serve as a novel PET tracer for imaging malignant tumors.

論文

Predicting cetuximab accumulation in ${it KRAS}$ wild-type and ${it KRAS}$ mutant colorectal cancer using $$^{64}$$Cu-labeled cetuximab positron emission tomography

Achmad, 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:17 パーセンタイル:42.64(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 (${it KRAS}$) mutation status has been established. In this study, we investigated cetuximab accumulation in colorectal tumors using $$^{111}$$In-DOTA-cetuximab, and evaluated the potential of positron emission tomography (PET) imaging of $$^{64}$$Cu-DOTA-cetuximab. We found that ${it KRAS}$ wild-type tumors had significantly higher $$^{111}$$In-DOTA-cetuximab accumulation than ${it KRAS}$ mutant tumors. Based on ${it KRAS}$ mutation status, a strong correlation was found between $$^{111}$$In-DOTA-cetuximab tumor uptake and EGFR expression level. Significant correlation was also found between tumor uptake of $$^{111}$$In-DOTA-cetuximab and $$^{64}$$Cu-DOTA-cetuximab. PET imaging with $$^{64}$$Cu-DOTA-cetuximab effectively visualized cetuximab accumulation in colorectal tumors with a wide variety of EGFR expression levels and different ${it KRAS}$ 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.

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

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:7 パーセンタイル:62.43(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

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:27 パーセンタイル:33.99(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:13 パーセンタイル:51.36(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.

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*; 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 $$^{18}$$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, $$^{64}$$Cu and $$^{76}$$Br have appropriate properties ($$^{76}$$Br: T$$_{1/2}$$ = 16.1hr, $$^{64}$$Cu: T$$_{1/2}$$ = 12.7hr) and they may have great potentials for PET utility. In this study, we synthesized monoclonal antibody (mAb) labeled with $$^{64}$$Cu or $$^{76}$$Br and evaluated their potential for tumor diagnosis with PET. The results of tumor localization studies show that $$^{64}$$Cu or $$^{76}$$Br labeled mAb were highly accumulated to tumor. From these data, the use of $$^{64}$$Cu and $$^{76}$$Br has great advantage for PET utility.

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*; 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 $$beta$$-particle-emitter, such as $$^{90}$$Y (2.28 MeV), seems particularly well suited for the treatment of relatively large tumor masses, but the middle energy $$beta$$-particles, such as $$^{67}$$Cu (0.18-0.58 MeV), may have an advantage in treating small lesions. In this study, we prepared $$^{67}$$Cu and evaluated its potential of application for RIT in tumor bearing mice. Our results of tumor localization studies show that $$^{67}$$Cu was expected to be suitable for RIT.

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

$$^{76}$$Br- or $$^{64}$$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 $$^{18}$$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, $$^{64}$$Cu and $$^{76}$$Br have appropriate properties ($$^{76}$$Br: T$$_{1/2}$$ = 16.1 hr, $$^{64}$$Cu: T$$_{1/2}$$ = 12.7 hr) and they may have great potentials for PET utility. In this study, we synthesized monoclonal antibody (mAb) labeled with $$^{64}$$Cu or $$^{76}$$Br and evaluated their potential for tumor diagnosis with PET. The results of tumor localization studies show that $$^{64}$$Cu or $$^{76}$$Br labeled mAb were highly accumulated to tumor. From these data, the use of $$^{64}$$Cu and $$^{76}$$Br has great advantage for PET utility.

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

PET-Optical Imagingによるマルチモダリティイメージングの有用性

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、$$^{64}$$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。

口頭

Production and utilization of new radioisotopes for theraputic and diagnostic applications in cancer

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. $$^{64}$$Cu and $$^{76}$$Br have appropriate properties ($$^{64}$$Cu: T$$_{1/2}$$ = 12.7 hr, $$^{76}$$Br: T$$_{1/2}$$ = 16.1 hr) and they may have great potentials for immuno-PET. We have synthesized $$^{64}$$Cu or $$^{76}$$Br labeled monoclonal antibody and evaluated potentials for in vivo quantitative evaluation of RIT. And we synthesized $$^{76}$$Br labeled glucose ($$^{76}$$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.

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.

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