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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:19 パーセンタイル:62.77(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.
渡辺 智; 橋本 和幸; 渡辺 茂樹; 飯田 靖彦*; 花岡 宏史*; 遠藤 啓吾*; 石岡 典子
Journal of Radioanalytical and Nuclear Chemistry, 303(1), p.935 - 940, 2015/01
被引用回数:14 パーセンタイル:73.72(Chemistry, Analytical)No-carrier-added Lu produced via the Yb(n, ) Yb Lu process was separated from the macroscopic amounts of the Yb target using reversed-phase ion-pair liquid chromatography. To produce a highly purified Lu solution capable of labeling antibodies, the metallic impurities were removed using cation, chelating ion, and anion exchange columns. After the elimination of metallic impurities, the concentrations of Ca, Fe, and Zn were reduced from 87, 340, and 77 ppb to 13, 18, and 9 ppb, respectively. Consequently, the labeling yield of the Lu -labeled antibody increased from less than 5% to 88%.
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:48.78(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.
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。
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:27 パーセンタイル:57.49(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.
渡辺 智; 渡邉 茂樹; 飯田 靖彦*; 花岡 宏史*; 遠藤 啓吾*; 石岡 典子
JAEA-Review 2011-043, JAEA Takasaki Annual Report 2010, P. 92, 2012/01
現在PET診断に用いられている核種は半減期が2時間以下と非常に短いため、抗体のような集積に時間のかかる化合物を利用したPET診断には限界がある。これを解決するために、本研究では新規ポジトロン放出核種として半減期が16.2時間のBrの製造法の開発を行った。セレン化銅をターゲットとし、Se(p,n) Br反応を用い、原子力機構のTIARA-AVFサイクロトロンからの20MeV, Hビームで照射をしてBrを生成した。Brの回収にはターゲット由来の毒物であるSeの混入を防ぐために乾式蒸留法を採用し、Brトラップ回収条件等の検討により、Brの高純度分離を達成した。分離条件については、回収方法及び電気炉内温度の最適化により、ターゲット中に生成した全Brの放出及びテフロンチューブ内でのロスの低減により、30%程度の回収率を約80%にまで向上させることに成功した。
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-[F]Fluoro--methyl-L-tyrosine ([F]FAMT) is a useful amino acid tracer for PET imaging of malignant tumors. FAMT analogs labeled with Br, a positron emitter with a long half-life (t=16.1 h), could be widely used as tracers for tumor imaging. In this study, 3-[Br]bromo--methyl-L-tyrosine ([Br]BAMT) was designed, and its usefulness was evaluated as a novel PET tracer for imaging malignant tumors. In this study, both [Br]BAMT and [Br]BAMT were prepared. [Br]BAMT was stable in vitro, but was catabolized after administration in mice. Cellular accumulation and retention of [Br]BAMT using LS180 colon adenocarcinoma cells were significantly higher than those of [F]FAMT. In biodistribution studies using LS180 tumor-bearing mice, the tumor accumulation of [Br]BAMT was higher than that of [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 [F]FAMT. PET imaging with [Br]BAMT enabled clear visualization of the tumor. In conclusion, although an improvement in stability is still needed, Br-labeled FAMT analogs could potentially serve as PET tracers for the imaging of malignant 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:14 パーセンタイル:46.62(Radiology, Nuclear Medicine & Medical Imaging)3-[F]fluoro--methyl-L-tyrosine ([F]FAMT) is a useful amino acid tracer for positron emission tomography (PET) imaging of malignant tumors. FAMT analogs labeled with Br, a positron emitter with a long half-life (=16.1 h), could be widely used as tracers for tumor imaging. In this study, 3-[Br]bromo--methyl-L-tyrosine ([Br]BAMT) was designed, and its usefulness was evaluated as a novel PET tracer for imaging malignant tumors. In this study, both [Br]BAMT and [Br]BAMT were prepared. [Br]BAMT was stable in vitro, but was catabolized after administration in mice. Cellular accumulation and retention of [Br]BAMT using LS180 colon adenocarcinoma cells were significantly higher than those of [F]FAMT. In biodistribution studies using LS180 tumor-bearing mice, the tumor accumulation of [Br]BAMT was higher than that of [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 [F]FAMT. PET imaging with [Br]BAMT enabled clear visualization of the tumor. In conclusion, although an improvement in stability is still needed, Br-labeled FAMT analogs could potentially serve as PET tracers for the imaging of malignant tumors.
渡邉 茂樹; 花岡 宏史*; Liang, J. X.*; 飯田 靖彦*; 渡辺 智; 遠藤 啓吾*; 石岡 典子
JAEA-Review 2010-065, JAEA Takasaki Annual Report 2009, P. 107, 2011/01
I--Iodobenzylgunanidine (I-MIBG), functional analogue of norepinephrine, has been employed for the therapy of neuroendcrine tumors which express norepinephrine transporter (NET). I-MIBG scintigraphy has been also used for diagnosis of NET positive tumors such as detecting metastasis, investigating suitability and monitoring response to the treatment with I-MIBG. However, I-MIBG scintigraphy has limitation to diagnose small legions due to its lower sensitivity and spatial resolution. Since positron emission tomography (PET) is superior to scintigraphy, positron emitter labeled MIBG has potential to improve diagnostic ability of NET positive neuroendcrine tumors. Then, we have reveal the utility of positron emitter Br labeled m-bromobenzylguanidine (Br-MBBG) as a PET tracer for NET positive tumor.
渡辺 智; 橋本 和幸; 花岡 宏史*; 遠藤 啓吾*; 石岡 典子
JAEA-Review 2010-065, JAEA Takasaki Annual Report 2009, P. 109, 2011/01
がん治療に有用な線放出核種であるLu(半減期6.7日)の製造研究(Yb(n,)Yb(T=1.911h)Lu)では、逆相シリカゲルカラム法による抗体標識が可能な高純度無担体Luの分離・精製法の開発に成功している。しかし、本法では、ターゲット物質であるYbOが2mg以上であると無担体Luを完全に分離することができないことが臨床応用に向けてのLuの大量製造の課題であった。そこで、精密分離前に粗分離を行い、分離可能な最大ターゲット重量を検討した。その結果、固相抽出分離カラムによる粗分離の導入により、YbO量が10mgまで分離可能であることを明らかにした。なお、YbO量10mgは、JRR-3(中性子束110ncms)で10日間照射することにより3.6GBqのLu(計算値)が生成するターゲット量に相当するので、臨床応用に必要なGBqオーダーの製造が本研究により理論上達成可能となった。今後は、固相抽出分離カラムと逆相シリカゲルカラム(精密分離)とを組合せ、GBqオーダーの高純度無担体Luの製造法の確立を目指す。
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 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.
渡邉 茂樹; 花岡 宏史*; Liang, J. X.; 飯田 靖彦*; 遠藤 啓吾*; 石岡 典子
Journal of Nuclear Medicine, 51(9), p.1472 - 1479, 2010/09
被引用回数:21 パーセンタイル:56.09(Radiology, Nuclear Medicine & Medical Imaging)-iodobenzylguanidine (MIBG) labeled has been widely used for the diagnosis and radiotherapy of norepinephrine transporter (NET)-expressing tumors. This study demonstrated that a positron emitter Br labeled -bromobenzylguanidine (Br-MBBG) was prepared and evaluated as a potential PET tracer for imaging NET-expressing tumors. Br-MBBG was stable in vitro, but some time-dependent dehalogenation was observed after administration in normal mice. MBBG showed high uptake in PC-12 tumor cells, and this uptake was significantly decreased by the addition of NET inhibitors. In biodistribution, MBBG showed high tumor accumulation (32.0 18.6% ID/g at 3 h p.i.) and the tumor-to-blood ratio reached as high as 54.4 31.9. Tumor uptake of MBBG correlated very well with that of I-MIBG (r = 0.997), but not with F-FDG. MBBG-PET showed a very clear image of the transplanted tumor with high sensitivity, and the visualized lesion was different from that by FDG-PET. These results indicated that Br-MBBG would be a potential PET tracer for imaging NET-expressing neuroendocrine tumors, and could provide useful information for determining the indications for I-MIBG therapy.
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:40 パーセンタイル:67.45(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.
渡邉 茂樹; 花岡 宏史*; Liang, J. X.; 飯田 靖彦*; 渡辺 智; 遠藤 啓吾*; 石岡 典子
JAEA-Review 2009-041, JAEA Takasaki Annual Report 2008, P. 107, 2009/12
I-m-Iodobenzylgunanidine (I-MIBG), functional analogue of norepinephrine, has been employed for the therapy of neuroendcrine tumors which express norepinephrine transporter (NET). I-MIBG scintigraphy has been also used for diagnosis of the neuroendcrine tumors. However, MIBG scintigraphy has been not enough for diagnosis of neuroendcrine tumors due to poor sensitivity and resolution. Positron emission tomography (PET) is superior to spatial resolution and quantitative capability. To improve diagnostic ability of NET positive neuroendcrine tumor, positron emitter Br labeled m-bromobenzylguanidine (Br-MBBG) was synthesized. Br was synthesized successfully with 50% of labeling efficiency, and the compound had great stability in vitro. In biodistribution studies using neuroendcrine tumor xenografted nude mice, Br-MBBG showed highest accumulation to the tumor, which is relative high compared to that of MIBG. These results indicate that Br-MBBG is useful for in vivo imaging of neuroendcrine tumors with PET.
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.
渡辺 智; 橋本 和幸; 渡邉 茂樹; 飯田 靖彦*; 花岡 宏史*; 遠藤 啓吾*; 石岡 典子
JAEA-Review 2009-041, JAEA Takasaki Annual Report 2008, P. 109, 2009/12
われわれは、がんに特異的に濃集するLu-抗体を開発し、がん治療薬としての有用性を評価することを目指している。そのためには、高純度で無担体のLuが必要である。そこで、本研究では、Lu-抗体の合成が可能な無担体Luの製造法の開発を行った。濃縮YbOターゲットを原子炉JRR-3で照射し、Yb(n, ) Yb(半減期1.91時間)Lu反応でLuを作製した。照射済みの濃縮YbOを塩酸で溶解し、逆相シリカゲルカラムにチャージし、あらかじめ不純物元素を取り除くために陽イオン交換カラム及びキレート交換カラムで精製した0.25M 2-ヒドロキシイソ酪酸(2-HIBA)/0.1M 1-オクタンスルホン酸ナトリウム(1-OS)を溶離液として用い、LuとターゲットであるYbとを分離した。分離後のLuフラクションを陽イオン交換カラムに通して2-HIBA/1-OSを完全に除去し、さらに残った不純物元素を取り除くために陰イオン交換カラムを通して最終Lu溶液を得た。このLuを用いてLu-抗体の標識実験を行った結果、標識率は80%以上であることがわかり、抗体への標識が可能な高純度無担体Luの製造が可能となった。
渡邉 茂樹; 渡辺 智; Liang, J. X.; 花岡 宏史*; 遠藤 啓吾*; 石岡 典子
Nuclear Medicine and Biology, 36(6), p.587 - 590, 2009/09
被引用回数:7 パーセンタイル:25.34(Radiology, Nuclear Medicine & Medical Imaging)We have developed a production method for no-carrier-added copper-64 (Cu) by using chelating resin bearing iminodiacetic acid groups. We optimized the condition for selective separation of radioactive copper by using chelating resin from nickel and cobalt. Radioactive copper was separated completely using 0.1 M and 2 M HCl solution. In production of no-carrier-added Cu, the average 87% of Cu was isolated from the NiO target with high radionuclide purity ( 99%). In order to investigate the quality of the obtained Cu, metallic impurities contained in the Cu solution were analyzed by means of inductive coupled-plasma mass spectroscopy (ICP-MS) and optical emission spectroscopy (ICP-OES). It was observed that extremely low amounts of metal ion were contained in the Cu. The Cu solution showed high specific activity (average: 594.7 GBq/mol). In this study, the chelating exchange method yielded high-quality of Cu sufficient for the synthesis of Cu-labeled radiopharmaceuticals and medical applications.
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:49.69(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.
渡邉 茂樹; 飯田 靖彦*; 鈴井 伸郎; 片渕 竜也*; 石井 里美; 河地 有木; 花岡 宏史*; 渡辺 智; 松橋 信平; 遠藤 啓吾*; et al.
Journal of Radioanalytical and Nuclear Chemistry, 280(1), p.199 - 205, 2009/04
被引用回数:24 パーセンタイル:81.69(Chemistry, Analytical)Copper-64 was produced by the Ni(p,n)Cu reaction using enriched-NiO target. We investigated and compared the production yield of Cu for proton beams of various energies by using a thick target. Enriched-Ni was recovered with high yield by simple procedures. Imaging studies using positron emission tomography (PET) and positron emitting tracer imaging system (PETIS) were performed. We obtained clear images in PET and PETIS studies. The results of this study indicate that Cu can be utilized as a biomedical tracer for the molecular imaging both in animals and plants.
奥 浩之*; 山田 圭一*; 小林 京子*; 片貝 良一*; Ashfaq, M.*; 花岡 宏史*; 飯田 靖彦*; 遠藤 啓吾*; 長谷川 伸; 前川 康成; et al.
Peptide Science 2008, p.439 - 442, 2009/03
マラリアは、熱帯及び亜熱帯地域における主な死因の一つである。これまでの研究において、エノラーゼ基質結合部位の部分配列に由来する人工ペプチド抗原としてマラリアワクチン抗原の有用性を検証してきた。人工抗原ペプチドは、抗原性ペプチドに5(6)-カルボキシフルオロセインを用いて蛍光ラベルして合成した。合成したペプチドは、乳酸とグリコール酸の共重合体(PLGA)を用いて乳化重合後、ホモジナイズし、ナノ粒子化した。この粒子へ再度0.5%ポリビニルアルコールを加えた後、乳化,ホモジナイズして粒子径0.3から1.5mmのナノ粒子を調製した。蛍光強度からみた生体外での徐放試験において、ペプチド抗原のみから作製したナノ球体を用いた場合、薬剤は、保留日数に対してほぼ0次で急激に放出されるのに比べ、PLGAナノ粒子に調製した試料は、1g/7日間で徐放されることがわかった。1.0mg(蛍光入り薬剤4.0g)のナノ粒子を用いたハダカネズミによる生体内試験において、蛍光強度は、12日間かけ次第に減少し、今回調製されたナノ微粒子は持続的に抗原を徐放することがわかった。