検索対象:     
報告書番号:
※ 半角英数字
 年 ~ 
 年
検索結果: 9 件中 1件目~9件目を表示
  • 1

発表形式

Initialising ...

選択項目を絞り込む

掲載資料名

Initialising ...

発表会議名

Initialising ...

筆頭著者名

Initialising ...

キーワード

Initialising ...

使用言語

Initialising ...

発行年

Initialising ...

開催年

Initialising ...

選択した検索結果をダウンロード

論文

Individual dosimetry system for targeted alpha therapy based on PHITS coupled with microdosimetric kinetic model

佐藤 達彦; 古田 琢哉; Liu, Y.*; 仲 定宏*; 永森 收志*; 金井 好克*; 渡部 直史*

EJNMMI Physics (Internet), 8, p.4_1 - 4_16, 2021/01

 被引用回数:2 パーセンタイル:90.15(Radiology, Nuclear Medicine & Medical Imaging)

標的$$alpha$$核医学治療は、高い治療効果と低い副作用を兼ね備えた新しいがん治療方法として注目を集めているが、その治療計画に患者の個性(体格や薬剤集積性など)は反映されていなかった。そこで本研究では、患者個人のPET-CT画像から自動で体内の積算放射能分布を推定し、PHITSを用いて吸収線量分布を計算するシステムを構築した。$$alpha$$線の高い細胞殺傷効果や腫瘍内における薬剤不均一性を考慮し、同じ効果を与えるX線治療の線量(等効果線量)を推定する新しいモデルを確立した。構築したシステムは、PET用核種をラベルした新しいプローブ(NKO-035)を健常者に投与した臨床試験結果を用いて検証した。その結果、重要臓器の吸収線量は、従来手法と比べて最大で20%程度の差があることが分かった

論文

Development of a widely usable amino acid tracer; $$^{76}$$Br-$$alpha$$-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:15 パーセンタイル:65.72(Radiology, Nuclear Medicine & Medical Imaging)

Radiolabeled amino acids are superior PET tracers for imaging of malignant tumors, and amino acids labeled with $$^{76}$$Br, an attractive positron emitter due to its relatively long half-life (t$$_{1/2}$$=16.2 h), could potentially be widely usable tumor imaging tracer. In this study, in consideration of stability and tumor specificity, 2-$$^{76}$$Br-bromo-$$alpha$$-methyl-L-phenylalanine (2-$$^{76}$$Br-BAMP) and 4-$$^{76}$$Br-bromo-$$alpha$$-methyl-L-phenylalanine (4-$$^{76}$$Br-BAMP) were designed and their potential as a tumor imaging agent was evaluated. No-carrier-added $$^{76}$$Br and $$^{77}$$Br, the latter of which is suitable radiobromine for basic studies due to its longer half-life (t$$_{1/2}$$ = 57.1 h), were produced. Both $$^{77}$$Br-BAMPs were stable in the plasma and in the murine body. In biodistribution studies, 2-$$^{77}$$Br-BAMP showed more rapid blood clearance and lower renal accumulation than did 4-$$^{77}$$Br-BAMP. More than 90% of injected radioactivity was excreted in the urine by 6 h post-injection of 2-$$^{77}$$Br-BAMP. High tumor accumulation of 2-$$^{77}$$Br-BAMP was observed in tumor-bearing mice and PET imaging with 2-$$^{76}$$Br-BAMP enabled clear visualization of the tumor. These findings suggest that 2-$$^{76}$$Br-BAMP would constitute a potential new PET tracer for tumor imaging and may eventually enable the wider use of amino acid tracers.

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:89 パーセンタイル:95.79(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

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:51 パーセンタイル:85.76(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:13 パーセンタイル:51.48(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.

口頭

3-[$$^{18}$$F]fluoro-$$alpha$$-methyl-D-tyrosine(D-[$$^{18}$$F]FAMT)のPET用新規アミノ酸トレーサーとしての生物学的評価

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.

no journal, , 

3-[$$^{18}$$F]Fluoro-$$alpha$$-methyl-L-tyrosine(L-[$$^{18}$$F]FAMT)は臨床応用される有用なPositron Emission Tomography(PET)用アミノ酸トレーサーであるが、正常組織である腎臓及び膵臓に対しても高度に集積・滞留する。一方で、非天然アミノ酸であるD体アミノ酸は、L体に比べ正常組織への分布が非常に低く、速やかな血液クリアランス及び癌組織集積性を示すことから、D体アミノ酸を利用することで明瞭かつ癌組織選択的なPETイメージングを実現できる可能性がある。そこで、本研究では3-[$$^{18}$$F]fluoro-$$alpha$$-methyl-D-tyrosine(D-[$$^{18}$$F]FAMT)を合成し、PET用アミノ酸トレーサーとしての有用性について検討した。体内分布実験の結果、D-[$$^{18}$$F]FAMTは非常に早い血液クリアランスを示し、投与直後に腎臓,膵臓への集積が認められたが、L-[$$^{18}$$F]FAMTのような滞留は認められず、速やかに消失した。また、D-[$$^{18}$$F]FAMTの癌組織集積量はL-[$$^{18}$$F]FAMTに比べて低かったが、正常組織分布も非常に低く、放射能の腫瘍血液比,腫瘍筋肉比はL-[$$^{18}$$F]FAMTと同等な高値を示した。さらにPETイメージングの結果、D-[$$^{18}$$F]FAMTによってL-[$$^{18}$$F]FAMTに比べて明瞭かつ癌組織選択的なPETイメージングが可能であることが示された。以上の結果より、D-[$$^{18}$$F]FAMTがPET用新規アミノ酸トレーサーとして有用であることが示唆された。

口頭

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.

no journal, , 

3-[$$^{18}$$F]Fluoro-$$alpha$$-methyl-L-tyrosine (L-[$$^{18}$$F]FAMT) is a useful amino acid tracer, and it is selectively accumulated in the tumor without an incorporation in the protein synthesis. However, L-[$$^{18}$$F]FAMT is highly retained in the kidney, which causes the reduction of sensitivity for tumor detection by positron emission tomography (PET). L-amino acids have corresponding D-isomers which have some favorable properties for development of PET tracers. Since mammals rarely use D-amino acids for their biological activity, D-amino acids would not be taken up by the normal tissues. In addition, D-amino acids are highly excreted in the urine compared with L-isomers, and rapidly cleared from the circulation. Thus, D-isomer of FAMT would lower the high retention of L-isomer in the kidney and allow clear imaging of the tumor by PET. In this study, we synthesized 3-[$$^{18}$$F]fluoro-$$alpha$$-methyl-D-tyrosine (D-[$$^{18}$$F]FAMT) and evaluated its potential. In biodistribution studies, D-[$$^{18}$$F]FAMT showed rapid clearance from blood, marked accumulation and retention in the tumor and low retention in non-target organs, especially kidney. Furthermore, PET imaging using D-[$$^{18}$$F]FAMT enabled clear visualization of implanted tumor, compared with L-[$$^{18}$$F]FAMT. In conclusion, D-[$$^{18}$$F]FAMT could potentially serve as a useful tracer for imaging malignant tumors.

口頭

Possibility of system L amino acid transporter 1 (LAT1) as a novel therapeutic target for biliary tract cancer

大島 康宏; 富永 英之*; 永森 收志*; 金井 好克*; 織内 昇*; 石岡 典子

no journal, , 

The expression of system L amino acid transporter 1 (LAT1) has been described to play essential roles in tumor growth and survival. In this study, we investigated whether LAT1 could be a novel therapeutic target for biliary tract cancer. Both expression of LAT1 and CD98 was found, and the expression of LAT1 was extremely higher than other subtypes of LAT in a biliary tract cancer cell line, HuCCT1. The uptake of [$$^{14}$$C]L-leucine was strongly inhibited by the treatment of BCH, an selective inhibitor of LAT1 and LAT2. These results indicate that the contribution of LAT1 to the uptake of amino acids was higher than other subtypes of LAT, and BCH could suppress the uptake of amino acids through LAT1 relatively. BCH decreased numbers of viable cells in a concentration-dependent manner ${it in vitro}$. Furthermore, daily injection of BCH to HuCCT1-bearing mice showed significant delay of tumor growth with no change of body-weight. These results suggest that LAT1 inhibition could suppress growth of biliary tract cancer. Inhibition of LAT1 would be an effective target for the therapy of this distressing disease.

口頭

新規PETイメージング用$$^{76}$$Br標識アミノ酸2-$$^{76}$$Br-bromo-$$alpha$$-methyl-L-phenylalanineの開発

大島 康宏; 花岡 宏史*; 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.

no journal, , 

本研究では、より生体内安定性の高い$$^{76}$$Br標識アミノ酸として、新たに2-$$^{76}$$Br-bromo-$$alpha$$-methyl-L-phenylalanine (2-$$^{76}$$Br-BAMP)を合成し、新規PETイメージング薬としての有用性について検討した。放射性Br($$^{76}$$Br及び$$^{77}$$Br)はセレン化銅ターゲットに対してプロトンビーム(20MeV)を照射することで製造した。$$^{76}$$Brは半減期16.2時間の陽電子放出核種であることからPETイメージングに使用し、$$^{77}$$Brは半減期57.1時間の$$gamma$$線放出核種であることから基礎検討に使用した。酸化剤存在下において、放射性Brと標識前駆体(2-trimethylstannyl-N-trifluoroacetyl-$$alpha$$-methyl-L-phenylalanine methyl ester)を反応させ、2-$$^{76}$$Br-BAMP及び2-$$^{77}$$Br-BAMPを合成した。HPLC分析の結果、標識率52.6$$pm$$11.9%、放射化学的純度95%以上で2-$$^{77}$$Br-BAMPの合成が可能であった。血清及びマウス体内における2-$$^{77}$$Br-BAMPの分解はほとんど認められず、非常に高い安定性を示した。体内分布では、2-$$^{77}$$Br-BAMPは癌へ高度に集積する一方、血中からの消失は早く、投与放射能の90%以上が6時間以内に尿中に排泄され、正常臓器へ非常に低い集積を示した。さらに2-$$^{76}$$Br-BAMPを用いてPET撮像を行った結果、癌を明瞭にイメージングすることができた。これらの結果より、2-$$^{76}$$Br-BAMPの新規PETイメージング薬としての有用性が示唆された。

9 件中 1件目~9件目を表示
  • 1