※一部利用できない機能があります
| 1.
論文 |
論文
|
Effendia, Nurmaya ; Ogawa, Kazuma ; Mishiro, Kenji ; Takarada, Takeshi ; Yamada, Daisuke ; Kitamura, Yoji ; Shiba, Kazuhiro ; Maeda, Takehiko ; Odani, Akira ; 小川, 数馬 ; 三代, 憲司 ; 宝田, 剛志 ; 北村, 陽二 ; 柴, 和弘 ; 小谷, 明
概要:
金沢大学新学術創成研究機構<br />Platelet-derived growth factor receptor β (PDGFRβ) is a transmembrane tyrosine kinase receptor and it
…
is upregulated in various malignant tumors. Radiolabeled PDGFRβ inhibitors can be a convenient tool for the imaging of tumors overexpressing PDGFRβ. In this study, [125I]-1-(5-iodo-2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinoline-8-yl)piperidin-4-amine ([125I]IIQP) and [125I]-N-3-iodobenzoyl-1-(2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl)-piperidin-4-amine ([125I]IB-IQP) were designed and synthesized, and their potential as PDGFRβ imaging agents was evaluated. In cellular uptake experiments, [125I]IIQP and [125I]IB-IQP showed higher uptake by PDGFRβ-positive cells than by PDGFRβ-negative cells, and the uptake in PDGFRβ-positive cells was inhibited by co-culture with PDGFRβ ligands. The biodistribution of both radiotracers in normal mice exhibited hepatobiliary excretion as the main route. In mice inoculated with BxPC3-luc (PDGFRβ-positive), the tumor uptake of radioactivity at 1h after the injection of [125I]IIQP was significantly higher than that after the injection of [125I]IB-IQP. These results indicated that [125I]IIQP can be a suitable PDGFRβ imaging agent. However, further modification of its structure will be required to obtain a more appropriate PDGFRβ-targeted imaging agent with a higher signal/noise ratio. © 2017.<br />Embargo Period 12 months
続きを見る
|
||||
| 2.
論文 |
論文
|
Ogawa, Kazuma ; Ishizaki, Atsushi ; Takai, Kenichiro ; Kitamura, Yoji ; Makino, Akira ; Kozaka, Takashi ; Kiyono, Yasushi ; Shiba, Kazuhiro ; Odani, Akira ; 小川, 数馬 ; 北村, 陽二 ; 小阪, 孝史 ; 柴, 和弘 ; 小谷, 明
概要:
金沢大学新学術創成研究機構<br />67Ga-DOTA-(L-Asp)11 and 67Ga-DOTA-(L-Asp)14, which have been developed as bone imaging agents, showed
…
a high accumulation in bone and a rapid blood clearance in mice. However, peptides composed of D-amino acids are more stable in vivo than those composed of their L-equivalents. In this study, 67Ga-DOTA-(D-Asp)n (n = 2, 5, 8, 11, or 14) were synthesized using the Fmoc-based solid-phase methodology and evaluated. In hydroxyapatite binding assay, binding of 67Ga-DOTA-(D-Asp)n tended to increase with increasing length of the amino acid chain. 67Ga-DOTA-(D-Asp)11 and 67Ga-DOTA-(D-Asp)14 caused a high accumulation of radioactivity in the bones of the mice. However, the results for 67Ga-DOTA-(D-Asp)n and 67Ga-DOTA-(L-Asp)n were comparable. In urine analyses, the proportion of intact complex after injection of 67Ga-DOTA-(D-Asp)14 was significantly higher than that of 67Ga-DOTA-(L-Asp)14. Although 67Ga-DOTA-(D-Asp)14 was more stable than 67Ga-DOTA-(L-Asp)14, the properties of 67Ga-DOTA-(D-Asp)n and 67Ga-DOTA-(L-Asp)n as bone imaging agents may be comparable. © 2017 The Author(s).
続きを見る
|
||||
| 3.
論文 |
論文
|
Ogawa, Kazuma ; Fukuda, Tadahisa ; Han, Jaegab ; Kitamura, Yoji ; Shiba, Kazuhiro ; Odani, Akira
概要:
Background Release of radionuclides, such as 137Cs and 90Sr, into the atmosphere and the ocean presents an important pro
…
blem because internal exposure to 137Cs and 90Sr could be very harmful to humans. Chlorella has been reported to be effective in enhancing the excretion of heavy metals; thus, we hypothesized that Chlorella could also enhance the elimination of 137Cs or 90Sr from the body. We evaluated the potential of Chlorella as a decorporation agent in vitro and in vivo, using 85Sr instead of 90Sr. Methods In vitro experiments of adsorption of 137Cs and 85Sr to Chlorella were performed under wide pH conditions. The maximum sorption capacity of Chlorella to strontium was estimated using the Langmuir model. A 85Sr solution was orally administrated to mice pretreated with Chlorella. At 48 h after 85Sr administration, the biodistribution of radioactivity was determined. Results In the in vitro experiments, although 85Sr barely adsorbed to Chlorella at low pH, the 85Sr adsorption ratio to Chlorella increased with increasing pH. The maximum sorption capacity of Chlorella to strontium was 9.06 mg / g. 137Cs barely adsorbed to Chlorella under any pH conditions. In the biodistribution experiments, bone accumulation of radioactivity after 85Sr administration was significantly decreased in the Chlorella pretreatment group compared with the non-treatment control group. Conclusions In conclusion, these results indicated that Chlorella could inhibit the absorption of 90Sr into the blood and enhance the elimination of 90Sr from the body through adsorption in intestine. Further studies are required to elucidate the mechanism and the components of Chlorella needed for adsorption to strontium and could promote the development of more effective decorporation agents. © 2016 Ogawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
続きを見る
|
||||
| 4.
論文 |
論文
|
Ogawa, Kazuma ; Shiba, Kazuhiro ; Akhter, Nasima ; Yoshimoto, Mitsuyoshi ; Washiyama, Kohshin ; Kinuya, Seigo ; Kawai, Keiichi ; Mori, Hirofumi
概要:
金沢大学医薬保健研究域薬学系<br />It has been reported that sigma receptors are highly expressed in a variety of human tumors. In this
…
study, we selected (+)-2-[4-(4-iodophenyl)piperidino] cyclohexanol [(+)-pIV] as a sigma receptor ligand and evaluated the potential of radioiodinated (+)-pIV for tumor imaging and therapy. (+)-[125/131I]pIV was prepared by an iododestannylation reaction under no-carrier-added conditions with radiochemical purity over 99% after HPLC purification. Biodistribution experiments were performed by the intravenous injection of (+)-[125I]pIV into mice bearing human prostate tumors (DU-145). Blocking studies were performed by intravenous injection of (+)-[125I]pIV mixed with an excess amount of unlabeled sigma ligand into DU-145 tumor-bearing mice. For therapeutic study, (+)-[131I]pIV was injected at a dose of 7.4 MBq followed by measurement of the tumor size. In biodistribution experiments, (+)-[125I]pIV showed high uptake and long residence in the tumor. High tumor to blood and muscle ratios were achieved because the radioactivity levels of blood and muscle were low. However, the accumulations of radioactivity in non-target tissues, such as liver and kidney, were high. The radioactivity in the non-target tissues slowly decreased over time. Co-injection of (+)-[125I]pIV with an excess amount of unlabeled sigma ligand resulted in a significant decrease in the tumor/blood ratio, indicating sigma receptor-mediated tumor uptake. In therapeutic study, tumor growth in mice treated with (+)-[131I]pIV was significantly inhibited compared to that of an untreated group. These results indicate that radioiodinated (+)-pIV has a high potential for sigma receptor imaging in tumor and radionuclide receptor therapy. (Cancer Sci 2009). © 2009 Japanese Cancer Association.
続きを見る
|
||||
| 5.
論文 |
論文
|
Ogawa, Kazuma ; Takai, Kenichiro ; Kanbara, Hiroya ; Kiwada, Tatsuto ; Kitamura, Youji ; Shiba, Kazuhiro ; Odani, Akira
概要:
金沢大学医薬保健研究域薬学系<br />Introduction: 68Ga is a radionuclide of great interest as a positron emitter for positron emission t
…
omography (PET). To develop a new bone-imaging agent with radiogallium, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was chosen as a chelating site and Ga-DOTA complex-conjugated bisphosphonate, which has a high affinity for bone, was prepared and evaluated. Although we are interested in developing 68Ga-labeled bone imaging agents for PET, in these initial studies 67Ga was used because of its longer half-life. Methods: DOTA-conjugated bisphosphonate (DOTA-Bn-SCN-HBP) was synthesized by conjugation of 2-(4-isothiocyanatebenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid to 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (alendronate). 67Ga-DOTA-Bn-SCN-HBP was prepared by coordination with 67Ga, and its in vitro and in vivo evaluations were performed. Results: 67Ga-DOTA-Bn-SCN-HBP was prepared with a radiochemical purity of over 95% without purification. 67Ga-DOTA-Bn-SCN-HBP had great affinity for hydroxyapatite in binding assay. In biodistribution experiments, 67Ga-DOTA-Bn-SCN-HBP accumulated in bone rapidly but was hardly observed in tissues other than bone. Pretreatment of an excess amount of alendronate inhibited the bone accumulation of 67Ga-DOTA-Bn-SCN-HBP. Conclusions: 67Ga-DOTA-Bn-SCN-HBP showed ideal biodistribution characteristics as a bone-imaging agent. These findings should provide useful information on the drug design of bone imaging agents for PET with 68Ga. © 2010 Elsevier Inc. All rights reserved.
続きを見る
|
||||
| 6.
論文 |
論文
|
Matsuda, Hiroshi ; Kinuya, Keiko ; Tsuji, Shiro ; Terada, Hitoshi ; Shiba, Kazuhiro ; Kojima, Kazuhiko ; Mori, Hirofumi ; Sumiya, Hisashi ; Hisada, Kinichi
概要:
金沢大学大学院医学系研究科
|
||||
| 7.
論文 |
論文
|
Matsuda, Hiroshi ; Kinuya, Keiko ; Tsuji, Shiro ; Terada, Hitoshi ; Shiba, Kazuhiro ; Mori, Hirofumi ; Sumiya, Hisashi ; Hisada, Kinichi
概要:
金沢大学大学院医学系研究科
|
||||
| 8.
論文 |
論文
|
Ogawa, Kazuma ; Kawashima, Hidekazu ; Kinuya, Seigo ; Shiba, Kazuhiro ; Onoguchi, Masahisa ; Kimura, Hiroyuki ; Hashimoto, Kazuyuki ; Odani, Akira ; Saji, Hideo
概要:
Objective: Rhenium is one of the most valuable elements for internal radiotherapy because 186Re and 188Re have favorable
…
physical characteristics. However, there are problems when proteins such as antibodies are used as carriers of 186/188Re. Labeling methods that use bifunctional chelating agents such as MAG3 require the conjugation of the 186/188Re complex to protein after radiolabeling with the bifunctional chelating agent. These processes are complicated. Therefore, we planned the preparation by a simple method and evaluation of a stable 186/188Re-labeled antibody. For this purpose, we selected 186/188Re(I) tricarbonyl complex as a chelating site. In this study, A7 (an IgG1 murine monoclonal antibody) was used as a model protein. 186/188Re-labeled A7 was prepared by directly reacting a 186/188Re(I) tricarbonyl precursor, [186/188Re(CO)3(H2O)3]+, with A7. We then compared the biodistribution of 186/188Re-labeled A7 in tumor-bearing mice with 125I-labeled A7. Methods: For labeling A7, [186/188Re(CO)3(H2O)3]+ was prepared according to a published procedure. 186/188Re-labeled A7 (186/188Re-(CO)3-A7) was prepared by reacting [186/188Re(CO)3(H2O)3]+ with A7 at 43°C for 2 h. Biodistribution experiments were performed by the intravenous administration of 186/188Re-(CO)3-A7 solution into tumor-bearing mice. Results: 186Re-(CO)3-A7 and 188Re-(CO)3-A7 were prepared with radiochemical yields of 23 and 28%, respectively. After purification with a PD-10 column, 186/188Re-(CO)3-A7 showed a radiochemical purity of over 95%. In biodistribution experiments, 13.1 and 13.2% of the injected dose/g of 186Re-(CO)3-A7 and 188Re-(CO)3-A7, respectively, accumulated in the tumor at 24-h postinjection, and the tumor-to-blood ratios were over 2.0 at the same time point. Meanwhile, uptake of 125I-A7 in the tumor was almost the same as that of 186/188Re-(CO)3-A7 at 24-h postinjection. Blood clearances of 186/188Re-(CO)3-A7 were faster than those of 125I-A7. Conclusion: 186/188Re-labeled A7 showed high uptakes in the tumor. However, further modification of the labeling method would be necessary to improve radiochemical yields and their biodistribution. © 2009 The Japanese Society of Nuclear Medicine.
続きを見る
|
||||
| 9.
論文 |
論文
|
Kinuya, Seigo ; Li, Xiao-Feng ; Yokoyama, Kunihiko ; Mori, Hirofumi ; Shiba, Kazuhiro ; Watanabe, Naoto ; Shuke, Noriyuki ; Bunko, Hisashi ; Michigishi, Takatoshi ; Tonami, Norihisa
概要:
医薬保健研究域医学系<br />Peritoneal spread is one of major causes of mortality in colorectal cancer patients. In the current inve
…
stigation, the efficacy of radio-immunotherapy (RIT) with i.p. administration of an anti-colorectal cancer IgG1, 131 I-A7, was compared to that with i.v. administration in BALB/c female mice bearing peritoneal nodules of LS180 human colon cancer cells, at the same toxicity level. Distribution of either i.p. or i.v. administered 131 I-A7 and i.p. administered irrelevant 131 I-HPMS-1 was assessed. Based on the results of toxicity determination at increments of 2 MBq and estimated dosimetry, an i.p. dose of 11 MBq and an i.v. dose of 9 MBq were chosen for treatment. Mice were monitored for long-term survival: untreated mice (n=11), mice undergoing i.p. RIT with 131 I-A7 (n=11), mice undergoing i.v. RIT with 131 I-A7 (n=11) and mice undergoing non-specific i.p. RIT with 131 I-HPMS-1 (n=5). Intraperitoneal injection of 131 I-A7 produced faster and greater tumor accumulation than i.v. injection: 34.2±16.5% of the injected dose per g (% ID/ g) and 11.1±3.6% ID/g at 2 h, respectively (P<0.0001). Consequently, cumulative radioactivity in tumors was 1.73-fold higher with i.p. injection. 131 I-HPMS-1 did not show specific accumulation. Non-specific RIT with 131 I-HPMS-1 (mean survival, 26.0±2.5 days) did not affect the survival as compared to no treatment (26.7±1.9 days). Intravenous RIT with 131 I-A7 prolonged the survival of mice to 32.8±1.8 days (P<0.01). Intraperitoneal RIT with 131 I-A7 improved the survival more significantly and attained cure in 2 of 11 mice (P<0.05 vs. i.v. RIT). In conclusion, i.p. RIT is more beneficial in treating peritoneal carcinomatosis of colon cancer than i.v. RIT in a murine model.
続きを見る
|
||||
| 10.
論文 |
論文
|
Sugihara, Takahiro ; Munesue, Seiichi ; Yamamoto, Yasuhiko ; Sakurai, Shigeru ; Akhter, Nasima ; Kitamura, Yoji ; Shiba, Kazuhiro ; Watanabe, Takuo ; Yonekura, Hideto ; Hayashi, Yasuhiko ; Hamada, Jun-ichiro ; Yamamoto, Hiroshi
概要:
The cell-surface receptor for advanced glycation end-products (RAGE) has been implicated in the development of diabetic
…
vascular complications and Alzheimer's disease. RAGE has been considered to be involved in amyloid-β 1-42 (Aβ 1-42) uptake into brain. In the present study, we demonstrate that endogenous secretory RAGE (esRAGE), a decoy form of RAGE generated by alternative RNA processing, is able to inhibit Aβ 1-42 influx into mouse brain. Surface plasmon resonance and competitive binding assays revealed that human Aβ 1-42 interacted with human esRAGE within the immunoglobulin V type region. We next examined the uptake and distribution of 125I-labeled human Aβ 1-42 in various organs and body fluids of newly created mice overexpressing human esRAGE as well as RAGE-null and wild-type (WT) mice. The transition of the 125I-labeled Aβ 1-42 from circulation to brain parenchyma peaked at 30 min after the injection into WT mice, but this was significantly blunted in esRAGE-overexpressing and RAGE-null mice. Significant reduction in 125I-labeled Aβ 1-42-derived photo-stimulated luminescence were marked in ventricles, cerebral cortex, hippocampus, especially CA1 and CA3 regions, putamen, and thalamus. The results thus suggest the potential of esRAGE in protection against the development of Alzheimer's disease. © 2012 - IOS Press and the authors. All rights reserved.
続きを見る
|
