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  1. Article ; Online: Comparison of radioactive iodide uptake in the rat thyroid between oral and intravenous bolus administration.

    Kurosawa, Hiroyuki / Sakurai, Kazuhisa / Hasegawa, Hideaki / Uchida, Keisuke / Kasahara, Hiroyuki / Minamizawa, Takao / Nakajo, Masatoyo / Nakajo, Masayuki

    Annals of nuclear medicine

    2014  Volume 28, Issue 10, Page(s) 986–993

    Abstract: Objective: Radioiodide is commonly used to diagnose and treat hyperthyroidism and thyroid carcinoma. However, we could not find any experimental data that strictly compared the biodistribution and thyroid uptake of radioactive iodide between the oral ... ...

    Abstract Objective: Radioiodide is commonly used to diagnose and treat hyperthyroidism and thyroid carcinoma. However, we could not find any experimental data that strictly compared the biodistribution and thyroid uptake of radioactive iodide between the oral and intravenous (iv) routes with time. This prompted us to compare (123)I biodistribution and thyroid uptake to clarify the differences between oral and iv bolus administration in rats.
    Methods: The rats were divided into two groups, A and B (n = 5, each). In the first imaging experiment, Na(123)I solution (35 MBq/200 μL) was administered as a bolus to the rats orally in group A and intravenously in group B. Two weeks later, the second imaging experiment was performed as a crossover experiment. (123)I biodistribution was evaluated visually and quantitatively with a gamma camera at 10 min, 3, 6, 12, 24, and 48 h after (123)I administration. Thyroid uptake was compared between oral and iv groups. Correlation of (123)I thyroid uptake and whole-body excretion was evaluated. The area under the curve (AUC) of thyroid uptake was also calculated.
    Results: (123)I biodistribution differed visually during 6 h between the two groups. (123)I thyroid uptake was significantly higher in the iv group at 10 min (P < 0.05) and in the oral group at 6 or more hour time points (P < 0.005-P < 0.0001) and peaked at 12 h in both groups (oral: 24.4 ± 2.8 %ID, iv: 15.2 ± 2.8 %ID). (123)I thyroid uptake showed significant inverse correlations with whole-body excretion from 6 h (r = -0.799, P < 0.0001), and thereafter [12 h (r = -0.957, P < 0.0001), 24 h (r = -0.905, P < 0.0001) and 48 h (r = -0.893, P < 0.0001)], respectively. (123)I whole-body excretion was significantly higher in the iv group at each time point (P < 0.0001). The AUC of (123)I thyroid uptake was 1.6 times higher in the oral group than the iv group.
    Conclusions: These results suggest that radioiodide accumulates in the rat thyroid more effectively by oral than iv administration probably due to slower and lower (123)I clearance from the body in the oral administration when administered in a bolus fashion.
    MeSH term(s) Administration, Oral ; Animals ; Area Under Curve ; Cross-Over Studies ; Injections, Intravenous ; Iodine Radioisotopes/administration & dosage ; Iodine Radioisotopes/pharmacokinetics ; Male ; Radionuclide Imaging/instrumentation ; Radiopharmaceuticals/administration & dosage ; Radiopharmaceuticals/pharmacokinetics ; Random Allocation ; Rats, Wistar ; Sodium Iodide/administration & dosage ; Sodium Iodide/pharmacokinetics ; Stomach/diagnostic imaging ; Thyroid Gland/diagnostic imaging ; Time Factors
    Chemical Substances Iodine Radioisotopes ; Radiopharmaceuticals ; Sodium Iodide (F5WR8N145C)
    Language English
    Publishing date 2014-12
    Publishing country Japan
    Document type Comparative Study ; Journal Article
    ZDB-ID 1146984-5
    ISSN 1864-6433 ; 0914-7187
    ISSN (online) 1864-6433
    ISSN 0914-7187
    DOI 10.1007/s12149-014-0909-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Evaluation of hepatocyte growth factor plasmid therapeutic effect by 99mTc-hexakis-2-methyoxy-isobutylisonitrile blood flow scintigraphy in a rat model of hind limb ischemia.

    Nagano, Akio / Komatsuno, Takao / Kasahara, Hiroyuki / Minamizawa, Takao / Yamagami, Takuji / Okuyama, Chio / Nishimura, Tsunehiko

    Nuclear medicine communications

    2011  Volume 32, Issue 9, Page(s) 818–823

    Abstract: Objective: This study was conducted in an attempt to use blood flow scintigraphy with 99mTc-hexakis-2-methyoxy-isobutylisonitrile (99mTc-MIBI) for the evaluation of the angiogenic effect of hepatocyte growth factor (HGF) plasmid in a rat model of hind ... ...

    Abstract Objective: This study was conducted in an attempt to use blood flow scintigraphy with 99mTc-hexakis-2-methyoxy-isobutylisonitrile (99mTc-MIBI) for the evaluation of the angiogenic effect of hepatocyte growth factor (HGF) plasmid in a rat model of hind limb ischemia.
    Materials and methods: The femoral artery of the left hind limb of each rat was ligated to create a model of hind limb ischemia. Three weeks later, HGF plasmid (1.5 mg/1.1 ml/body) or saline (1.1 ml/body) was administered intramuscularly into three sites of the ischemic hind limb. Two and 4 weeks after the treatment, blood flow through the hind limb was measured by 99mTc-MIBI scintigraphy. In addition, the number of capillary endothelial cells obtained by immunostaining for CD31 was counted.
    Results: After 99mTc-MIBI scintigraphy in the HGF plasmid-treated group, the blood flow ratio increased significantly from the pretreatment ratio 63.8 to 73.4%, 2 weeks after treatment (P<0.05) and to 97.8%, 4 weeks after treatment (P<0.05). The number of CD31-positive endothelial cells was significantly higher in the HGF plasmid-treated group than in the control group.
    Conclusions: The experimental study using a rat model of hind limb ischemia showed usefulness of 99mTc-MIBI scintigraphy to evaluate the angiogenic effect of HGF plasmid treatment.
    MeSH term(s) Angiogenesis Modulating Agents/pharmacology ; Angiogenesis Modulating Agents/therapeutic use ; Animals ; Blood Circulation/drug effects ; Disease Models, Animal ; Endothelial Cells/diagnostic imaging ; Endothelial Cells/drug effects ; Endothelial Cells/metabolism ; Endothelial Cells/pathology ; Extremities/blood supply ; Extremities/diagnostic imaging ; Hepatocyte Growth Factor/genetics ; Humans ; Ischemia/diagnostic imaging ; Ischemia/drug therapy ; Ischemia/pathology ; Ischemia/physiopathology ; Plasmids/pharmacology ; Plasmids/therapeutic use ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; Radionuclide Imaging ; Rats ; Rats, Sprague-Dawley ; Technetium Tc 99m Sestamibi ; Treatment Outcome
    Chemical Substances Angiogenesis Modulating Agents ; Platelet Endothelial Cell Adhesion Molecule-1 ; Hepatocyte Growth Factor (67256-21-7) ; Technetium Tc 99m Sestamibi (971Z4W1S09)
    Language English
    Publishing date 2011-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 758141-5
    ISSN 1473-5628 ; 0143-3636
    ISSN (online) 1473-5628
    ISSN 0143-3636
    DOI 10.1097/MNM.0b013e328347a9d4
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  3. Article: Detection limit of measurement of pharmaceuticals labeled with short-lived isotopes in HPLC with flow-through gamma-counter.

    Kitajima, Akihito / Minamizawa, Takao / Toyo'oka, Toshimasa / Matsuda, Rieko / Hayashi, Yuzuru

    Journal of pharmaceutical and biomedical analysis

    2008  Volume 46, Issue 1, Page(s) 177–180

    Abstract: This paper proposes a method for estimating the detection limit, which is defined as 3.3 times the standard deviation (S.D.) of blank measurements under the situations where the repetition of measurement is difficult or impossible because of a short half- ...

    Abstract This paper proposes a method for estimating the detection limit, which is defined as 3.3 times the standard deviation (S.D.) of blank measurements under the situations where the repetition of measurement is difficult or impossible because of a short half-life of radioactivity. The FUMI theory, which can estimate an S.D. value without repetition in various instrumental analyses, is adopted and proved here to be available in a radio-HPLC system as well. (99m)Tc-ECD (T(1/2)=360.6 min) that is a lipophilic compound for the diagnosis of regional brain perfusion is taken as an example.
    MeSH term(s) Algorithms ; Chromatography, High Pressure Liquid/instrumentation ; Chromatography, High Pressure Liquid/methods ; Data Interpretation, Statistical ; Gamma Rays ; Half-Life ; Iodine Radioisotopes/analysis ; Isotopes/analysis ; Markov Chains ; Organotechnetium Compounds/analysis ; Probability ; Radiopharmaceuticals/analysis ; Reproducibility of Results ; Scintillation Counting/instrumentation ; Scintillation Counting/methods ; Sodium Isotopes/analysis ; Spectroscopy, Fourier Transform Infrared/methods ; Technology, Pharmaceutical/instrumentation ; Technology, Pharmaceutical/methods ; Time Factors
    Chemical Substances Iodine Radioisotopes ; Isotopes ; Organotechnetium Compounds ; Radiopharmaceuticals ; Sodium Isotopes
    Language English
    Publishing date 2008-01-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 604917-5
    ISSN 1873-264X ; 0731-7085
    ISSN (online) 1873-264X
    ISSN 0731-7085
    DOI 10.1016/j.jpba.2007.08.020
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  4. Article ; Online: Distinct binding of amyloid imaging ligands to unique amyloid-β deposited in the presubiculum of Alzheimer's disease.

    Ji, Bin / Chen, Chun-Jen / Bando, Kazunori / Ashino, Hiroki / Shiraishi, Hideaki / Sano, Hiroaki / Kasahara, Hiroyuki / Minamizawa, Takao / Yamada, Kazutaka / Ono, Maiko / Zhang, Ming-Rong / Seki, Chie / Farde, Lars / Suhara, Tetsuya / Higuchi, Makoto

    Journal of neurochemistry

    2015  Volume 135, Issue 5, Page(s) 859–866

    Abstract: Non-invasive determination of amyloid-β peptide (Aβ) deposition with radioligands serves for the early diagnosis and clarification of pathogenetic mechanisms of Alzheimer's disease (AD). The polymorphic binding site on multimeric Aβ for current ... ...

    Abstract Non-invasive determination of amyloid-β peptide (Aβ) deposition with radioligands serves for the early diagnosis and clarification of pathogenetic mechanisms of Alzheimer's disease (AD). The polymorphic binding site on multimeric Aβ for current radioligands, however, is little understood. In this study, we investigated the binding of several radioligands including (11)C-Pittsburgh Compound B ((11)C-PiB), (3)H-AZD2184, and two recently developed compounds, (125)I-DRM106 and (125)I-DRK092, with unique presubicular Aβ deposits lacking interaction with the commonly used amyloid dyes FSB. (11)C-PiB, (3)H-AZD2184, and (125)I-DRK092 showed overt binding to presubicular Aβ deposits, while (125)I-DRM106 barely bound to these aggregates despite its strong binding in the hippocampal CA1 sector. Unlike neuritic plaques in the CA1, Aβ lesions in the presubiculum were not accompanied by inflammatory gliosis enriched with 18-kDa translocator protein (TSPO). Thus, there are at least two different components in Aβ aggregates providing distinct binding sites for the current amyloid radioligands, and one of these binding components is distinctly present in the presubicular Aβ deposits. Amyloid radioligands lacking affinity for this component, such as (125)I-DRM106, may selectively capture Aβ deposits tightly associated with TSPO neuroinflammation and neurodegeneration as exemplified by CA1 neuritic plaques. Hence, comparative autoradiographic assessments of radioligand binding in CA1 and presubiculum could serve for the development of an amyloid PET imaging agent visualizing neurotoxicity-related Aβ pathologies. Non-invasive determination of amyloid-β peptide (Aβ) serves for the early diagnosis and clarification of pathogenetic mechanisms of Alzheimer's disease (AD). We found that there are at least two different amyloid components in hippocampal CA1 and presubiculum providing distinct binding sites for the current amyloid radioligands. Comparative analysis for radioligand binding in these two regions could serve for developing novel imaging agents selectively visualizing neurotoxicity-related Aβ pathologies.
    MeSH term(s) Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/pathology ; Aminopyridines/pharmacokinetics ; Amyloidogenic Proteins/metabolism ; Aniline Compounds/pharmacokinetics ; Autoradiography ; Benzothiazoles/pharmacokinetics ; Humans ; Imidazoles/pharmacokinetics ; In Vitro Techniques ; Parahippocampal Gyrus/diagnostic imaging ; Parahippocampal Gyrus/drug effects ; Parahippocampal Gyrus/metabolism ; Plaque, Amyloid/diagnostic imaging ; Plaque, Amyloid/pathology ; Positron-Emission Tomography ; Pyridines/pharmacokinetics ; Radiopharmaceuticals/pharmacokinetics ; Receptors, GABA/metabolism ; Thiazoles/pharmacokinetics ; Tomography, Emission-Computed, Single-Photon
    Chemical Substances 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole ; 2-(6-(methylamino)pyridin-3-yl)-1,3-benzothiazol-6-ol ; 6-iodo-2-(4-(1H-3-pyrazolyl)phenyl)imidazo(1,2-a)pyridine ; Aminopyridines ; Amyloidogenic Proteins ; Aniline Compounds ; Benzothiazoles ; Imidazoles ; Pyridines ; Radiopharmaceuticals ; Receptors, GABA ; TSPO protein, human ; Thiazoles
    Language English
    Publishing date 2015-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80158-6
    ISSN 1471-4159 ; 0022-3042 ; 1474-1644
    ISSN (online) 1471-4159
    ISSN 0022-3042 ; 1474-1644
    DOI 10.1111/jnc.13293
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  5. Article ; Online: Synthesis and evaluation of a novel 68Ga-chelate-conjugated bisphosphonate as a bone-seeking agent for PET imaging.

    Suzuki, Kentaro / Satake, Miho / Suwada, Jun / Oshikiri, Shinobu / Ashino, Hiroki / Dozono, Hiroyuki / Hino, Akihiro / Kasahara, Hiroyuki / Minamizawa, Takao

    Nuclear medicine and biology

    2011  Volume 38, Issue 7, Page(s) 1011–1018

    Abstract: Introduction: (68)Ga is a positron-emitting nuclide that has significant imaging potential given that, unlike cyclotron-produced (18)F, the isotope can be produced on-site utilizing a (68)Ge/(68)Ga generator. We recently synthesized a novel bone-seeking ...

    Abstract Introduction: (68)Ga is a positron-emitting nuclide that has significant imaging potential given that, unlike cyclotron-produced (18)F, the isotope can be produced on-site utilizing a (68)Ge/(68)Ga generator. We recently synthesized a novel bone-seeking agent by coupling a bisphosphonate with the (68)Ga chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). This study presents a first report on the potential of this (68)Ga bone-seeking radiopharmaceutical in the detection of bone metastases.
    Methods: 4-Amino-1-hydroxybutylidene-1,1-bisphosphonate was conjugated with 2-[4,7-di(carboxymethyl)-1,4,7-triazonan-1-yl]pentanedioic acid, yielding 2-[4,7-di(carboxymethyl)-1,4,7-triazonan-1-yl]-5-[(4-hydroxy-4,4-diphosphonobutyl)amino]-5-oxopentanoic acid (NOTA-BP). (68)Ga-labeled NOTA-BP ([(68)Ga]NOTA-BP) was prepared by complexation of NOTA-BP with [(68)Ga] gallium chloride and evaluated in in vitro experiments, biodistribution experiments and micro-positron emission tomography (PET) imaging experiments.
    Results: The labeling of NOTA-BP with (68)Ga was completed by heating for 10 min. [(68)Ga]NOTA-BP was determined to have a radiochemical purity of over 95%, a high affinity for hydroxyapatite and a high stability in plasma. In in vivo biodistribution experiments, [(68)Ga]NOTA-BP demonstrated high bone uptake potential. Compared with (99m)Tc-labeled methylene diphosphonate ([(99m)Tc]MDP) and [(18)F]fluoride, [(68)Ga]NOTA-BP exhibited faster blood clearance and a higher bone-to-blood ratio. In addition, mouse model bone metastasis was detected by micro-PET imaging at 1 h postinjection of [(68)Ga]NOTA-BP.
    Conclusion: We have developed a novel (68)Ga-radiolabeled bone-seeking agent. This [(68)Ga]NOTA-BP complex was found to have a high bone affinity and rapid blood clearance, and may thus prove to be useful as a bone-seeking agent for clinical PET.
    MeSH term(s) Animals ; Bone Neoplasms/diagnostic imaging ; Bone Neoplasms/physiopathology ; Bone Neoplasms/secondary ; Bone and Bones/diagnostic imaging ; Bone and Bones/metabolism ; Bone and Bones/physiopathology ; Cell Line, Tumor ; Chelating Agents/chemistry ; Diphosphonates/chemical synthesis ; Diphosphonates/metabolism ; Diphosphonates/pharmacokinetics ; Durapatite/metabolism ; Gallium Radioisotopes ; Heterocyclic Compounds/chemistry ; Humans ; Male ; Mice ; Osteolysis/diagnostic imaging ; Positron-Emission Tomography/methods ; Prostatic Neoplasms/pathology ; Radiopharmaceuticals/chemical synthesis ; Radiopharmaceuticals/metabolism ; Radiopharmaceuticals/pharmacokinetics ; Rats ; Reproducibility of Results
    Chemical Substances Chelating Agents ; Diphosphonates ; Gallium Radioisotopes ; Heterocyclic Compounds ; Radiopharmaceuticals ; 1,4,7-triazacyclononane-N,N',N''-triacetic acid (56491-86-2) ; Durapatite (91D9GV0Z28)
    Language English
    Publishing date 2011-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1138098-6
    ISSN 1872-9614 ; 0883-2897 ; 0969-8051
    ISSN (online) 1872-9614
    ISSN 0883-2897 ; 0969-8051
    DOI 10.1016/j.nucmedbio.2011.02.015
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  6. Article: (90)Y bremsstrahlung emission computed tomography using gamma cameras.

    Ito, Shigeki / Kurosawa, Hiroyuki / Kasahara, Hiroyuki / Teraoka, Satomi / Ariga, Eiji / Deji, Shizuhiko / Hirota, Masahiro / Saze, Takuya / Minamizawa, Takao / Nishizawa, Kunihide

    Annals of nuclear medicine

    2009  Volume 23, Issue 3, Page(s) 257–267

    Abstract: Objective: This study demonstrates images obtained by (90)Y bremsstrahlung emission computed tomography (BECT), and characterizes the system performance of gamma cameras.: Methods: (90)Y BECT images of phantoms were acquired using a gamma camera ... ...

    Abstract Objective: This study demonstrates images obtained by (90)Y bremsstrahlung emission computed tomography (BECT), and characterizes the system performance of gamma cameras.
    Methods: (90)Y BECT images of phantoms were acquired using a gamma camera equipped with a medium energy general purpose parallel-hole collimator. Three energy window widths of 50% (57-94 keV) centered at 75 keV, 30% (102-138 keV) at 120 keV, and 50% (139-232 keV) at 185 keV were set on a (90)Y bremsstrahlung spectrum. The images obtained with three energy windows were reconstructed using filtered back projection (FBP) and ordered subsets expectation maximization (OSEM) methods. The images of the sum window were obtained by fusing the images of the 75, 120, and 185 keV windows.
    Results: The OSEM method improved the full width at half maximum by 20% and the standard deviation by 9% compared with the FBP method. BECT displayed (90)Y biodistribution and quantified (90)Y activity. BECT images obtained with OSEM method using the 120 keV window showed the highest resolution and lowest uncertainty. The sum window showed the highest sensitivity, while its resolution was 10% inferior to that of the 120 keV window. One whole-body image can be taken over 100 min using the sum window. An absorber to cover the body surface reduced background by 30%.
    Conclusions: (90)Y BECT imaging can be used for patient assessment without modifying current treatment procedures.
    MeSH term(s) Absorption ; Gamma Cameras ; Heart Neoplasms/diagnostic imaging ; Liver Neoplasms/diagnostic imaging ; Phantoms, Imaging ; Radiography ; Sensitivity and Specificity ; Tomography, Emission-Computed/instrumentation ; Yttrium Radioisotopes
    Chemical Substances Yttrium Radioisotopes
    Language English
    Publishing date 2009-05
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 1146984-5
    ISSN 1864-6433 ; 0914-7187
    ISSN (online) 1864-6433
    ISSN 0914-7187
    DOI 10.1007/s12149-009-0233-9
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  7. Article ; Online: Biological evaluation of the radioiodinated imidazo[1,2-a]pyridine derivative DRK092 for amyloid-β imaging in mouse model of Alzheimer's disease.

    Chen, Chun-Jen / Bando, Kazunori / Ashino, Hiroki / Taguchi, Kazumi / Shiraishi, Hideaki / Shima, Keiji / Fujimoto, Osuke / Kitamura, Chiemi / Morimoto, Yasuaki / Kasahara, Hiroyuki / Minamizawa, Takao / Jiang, Cheng / Zhang, Ming-Rong / Suhara, Tetsuya / Higuchi, Makoto / Yamada, Kazutaka / Ji, Bin

    Neuroscience letters

    2014  Volume 581, Page(s) 103–108

    Abstract: Non-invasive determination of amyloid-β peptide (Aβ) deposition has important significance for early diagnosis and medical intervention in Alzheimer's disease (AD). In this study, we investigated the availability of a radioiodinated imidazo[1,2-a] ... ...

    Abstract Non-invasive determination of amyloid-β peptide (Aβ) deposition has important significance for early diagnosis and medical intervention in Alzheimer's disease (AD). In this study, we investigated the availability of a radioiodinated imidazo[1,2-a]pyridine derivative, termed (125)I-DRK092, as single photon emission computed tomography (SPECT) ligand for in vivo detection of Aβ deposition. DRK092 showed high binding affinity for either synthetic human Aβ fibrils or brain homogenates from amyloid precursor protein transgenic (Tg) mouse (PS1-ki/JU-Tg2576) and AD patient with a dissociation constant (Kd) of one-digit nM, and excellent brain permeability (peak value of uptake: approximately 0.9% of injection dose/g rat brain). Ex vivo autoradiographic analysis showed that measurement with (125)I-DRK092 has higher sensibility for detecting Aβ accumulation than with (125)I-IMPY, a well-known amyloid SPECT ligand, in Tg mice. In vitro autoradiography with (125)I-DRK092 also confirmed higher accumulation of radioactivity in the cortical area, enriched with Aβ plaques, of Tg mouse and AD patient brains, as compared with the corresponding areas in non-Tg mouse and healthy control brains. All the data presented above lead us to draw the conclusion that radioiodinated DRK092 is a potential SPECT ligand for amyloid imaging in AD.
    MeSH term(s) Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/metabolism ; Animals ; Autoradiography ; Brain/diagnostic imaging ; Brain/metabolism ; Disease Models, Animal ; Humans ; Imidazoles/chemistry ; Imidazoles/pharmacokinetics ; Iodine Radioisotopes ; Mice ; Plaque, Amyloid/diagnostic imaging ; Pyrazoles ; Pyridines/chemistry ; Pyridines/pharmacokinetics ; Rats ; Tomography, Emission-Computed, Single-Photon
    Chemical Substances Amyloid beta-Peptides ; DRK092 ; Imidazoles ; Iodine Radioisotopes ; Pyrazoles ; Pyridines ; 2,3-dihydro-1H-imidazo(1,2-b)pyrazole (MX6Z942BKY) ; pyridine (NH9L3PP67S)
    Language English
    Publishing date 2014-10-03
    Publishing country Ireland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 194929-9
    ISSN 1872-7972 ; 0304-3940
    ISSN (online) 1872-7972
    ISSN 0304-3940
    DOI 10.1016/j.neulet.2014.08.036
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  8. Article ; Online: Synthesis and biological evaluation of novel radioiodinated imidazopyridine derivatives for amyloid-β imaging in Alzheimer's disease.

    Chen, Chun-Jen / Bando, Kazunori / Ashino, Hiroki / Taguchi, Kazumi / Shiraishi, Hideaki / Fujimoto, Osuke / Kitamura, Chiemi / Matsushima, Satoshi / Fujinaga, Masayuki / Zhang, Ming-Rong / Kasahara, Hiroyuki / Minamizawa, Takao / Jiang, Cheng / Ono, Maiko / Higuchi, Makoto / Suhara, Tetsuya / Yamada, Kazutaka / Ji, Bin

    Bioorganic & medicinal chemistry

    2014  Volume 22, Issue 15, Page(s) 4189–4197

    Abstract: Non-invasive detection for amyloid-β peptide (Aβ) deposition has important significance for the early diagnosis and medical intervention for Alzheimer's disease (AD). In this study, we developed a series of imidazopyridine derivatives as potential ... ...

    Abstract Non-invasive detection for amyloid-β peptide (Aβ) deposition has important significance for the early diagnosis and medical intervention for Alzheimer's disease (AD). In this study, we developed a series of imidazopyridine derivatives as potential imaging agents for single-photon emission computed tomography (SPECT). Two of them, compounds DRK092 and DRM106, showed higher affinity for synthetic human Aβ 1-40 fibrils than did the well-known amyloid-imaging agent IMPY. A metabolite analysis revealed brain-permeable radioactive metabolites of (125)I-labeled DRK092 and IMPY; no radioactive metabolites from (125)I-labeled DRM106 ([(125)I]DRM106) were detected. In addition, in vitro autoradiography clearly demonstrated specific binding of [(125)I]DRM106 in the hippocampal region of AD enriched with Aβ plaques. Thus, our results strongly suggested that compound DRM106 can be used as an imaging agent for SPECT to detect Aβ deposition in AD brain.
    MeSH term(s) Alzheimer Disease/diagnosis ; Alzheimer Disease/metabolism ; Amyloid beta-Peptides/chemistry ; Amyloid beta-Peptides/metabolism ; Animals ; Autoradiography ; Brain/diagnostic imaging ; Hippocampus/metabolism ; Humans ; Imidazoles/chemistry ; Iodine Radioisotopes/chemistry ; Peptide Fragments/chemistry ; Peptide Fragments/metabolism ; Positron-Emission Tomography ; Pyridines/chemistry ; Pyridines/metabolism ; Radiopharmaceuticals/chemical synthesis ; Radiopharmaceuticals/metabolism ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution ; Tomography, Emission-Computed, Single-Photon
    Chemical Substances Amyloid beta-Peptides ; DRK092 ; Imidazoles ; Iodine Radioisotopes ; Peptide Fragments ; Pyridines ; Radiopharmaceuticals ; amyloid beta-protein (1-40)
    Language English
    Publishing date 2014-08-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1161284-8
    ISSN 1464-3391 ; 0968-0896
    ISSN (online) 1464-3391
    ISSN 0968-0896
    DOI 10.1016/j.bmc.2014.05.043
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  9. Article ; Online: In vivo SPECT imaging of amyloid-β deposition with radioiodinated imidazo[1,2-a]pyridine derivative DRM106 in a mouse model of Alzheimer's disease.

    Chen, Chun-Jen / Bando, Kazunori / Ashino, Hiroki / Taguchi, Kazumi / Shiraishi, Hideaki / Shima, Keiji / Fujimoto, Osuke / Kitamura, Chiemi / Matsushima, Satoshi / Uchida, Keisuke / Nakahara, Yuto / Kasahara, Hiroyuki / Minamizawa, Takao / Jiang, Cheng / Zhang, Ming-Rong / Ono, Maiko / Tokunaga, Masaki / Suhara, Tetsuya / Higuchi, Makoto /
    Yamada, Kazutaka / Ji, Bin

    Journal of nuclear medicine : official publication, Society of Nuclear Medicine

    2015  Volume 56, Issue 1, Page(s) 120–126

    Abstract: Unlabelled: Noninvasive determination of amyloid-β peptide (Aβ) deposition has important significance for early diagnosis and medical intervention for Alzheimer's disease (AD). In the present study, we investigated the availability of radiolabeled ... ...

    Abstract Unlabelled: Noninvasive determination of amyloid-β peptide (Aβ) deposition has important significance for early diagnosis and medical intervention for Alzheimer's disease (AD). In the present study, we investigated the availability of radiolabeled DRM106 ((123/125)I-DRM106 [6-iodo-2-[4-(1H-3-pyrazolyl)phenyl]imidazo[1,2-a]pyridine]), a compound with sufficient affinity for the synthesis of human Aβ fibrils and satisfactory metabolic stability, as a SPECT ligand in living brains.
    Method: The sensitivity of (125)I-DRM106 for detecting Aβ deposition was compared with that of (125)I-IMPY (2-(4'-dimethylaminophenyl)-6-iodo-imidazo[1,2-a]pyridine), a well-known amyloid SPECT ligand, by ex vivo autoradiographic analyses in 18-mo-old amyloid precursor protein transgenic mice. To verify the sensitivity and quantitation of radiolabeled DRM106 for in vivo imaging, we compared the detectability of Aβ plaques with (123)I-DRM106 and a well-known amyloid PET agent, (11)C-labeled Pittsburgh compound B ((11)C-PiB), in 29-mo-old transgenic mice and age-matched nontransgenic littermates. Additionally, we compared the binding characteristics of (125)I-DRM106 with those of (11)C-PiB and (11)C-PBB3, which selectively bind to Aβ plaques and preferentially to tau aggregates, respectively, in postmortem AD brain sections.
    Results: Ex vivo autoradiographic analysis showed that measurement with (125)I-DRM106 has a higher sensitivity for detecting Aβ accumulation than with (125)I-IMPY in transgenic mice. SPECT imaging with (123)I-DRM106 also successfully detected Aβ deposition in living aged transgenic mice and showed strong correlation (R = 0.95, P < 0.01) in quantitative analysis for Aβ plaque detection by PET imaging with (11)C-PiB, implying that sensitivity and quantitation of SPECT imaging with (123)I-DRM106 are almost as good as (11)C-PiB PET for the detectability of Aβ deposition. Further, the addition of nonradiolabeled DRM106 fully blocked the binding of (125)I-DRM106 and (11)C-PiB, but not (11)C-PBB3, to AD brain sections, and (125)I-DRM106 showed a lower binding ratio of the diffuse plaque-rich lateral temporal cortex to the dense-cored/neuritic plaque-rich hippocampal CA1 area, compared with (11)C-PiB.
    Conclusion: All of these data demonstrated the high potential of (123)I-DRM106 for amyloid imaging in preclinical and clinical application, and it might more preferentially detect dense-cored/neuritic amyloid deposition, which is expected to be closely associated with neuropathologic changes of AD.
    MeSH term(s) Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Animals ; Brain/diagnostic imaging ; Brain/metabolism ; Disease Models, Animal ; Humans ; Imidazoles/chemistry ; Iodine Radioisotopes ; Male ; Mice ; Peptide Fragments/metabolism ; Pyridines/chemistry ; Tomography, Emission-Computed, Single-Photon
    Chemical Substances 6-iodo-2-(4-(1H-3-pyrazolyl)phenyl)imidazo(1,2-a)pyridine ; Amyloid beta-Peptides ; Imidazoles ; Iodine Radioisotopes ; Peptide Fragments ; Pyridines ; amyloid beta-protein (1-40) ; amyloid beta-protein (1-42) ; pyridine (NH9L3PP67S)
    Language English
    Publishing date 2015-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80272-4
    ISSN 1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
    ISSN (online) 1535-5667
    ISSN 0097-9058 ; 0161-5505 ; 0022-3123
    DOI 10.2967/jnumed.114.146944
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Baseline noise and measurement uncertainty in liquid chromatography.

    Kitajima, Akihito / Kashirajima, Takeshi / Minamizawa, Takao / Sato, Hiroyasu / Iwaki, Kazuo / Ueda, Taisuke / Kimura, Yoshio / Toyo'oka, Toshimasa / Maitani, Tamio / Matsuda, Rieko / Hayashi, Yuzuru

    Analytical sciences : the international journal of the Japan Society for Analytical Chemistry

    2007  Volume 23, Issue 9, Page(s) 1077–1080

    Abstract: The stochastic properties of baseline noise in HPLC systems with a UV photo-diode array, photo-multiplier and gamma-ray detector were examined by dividing the noise into auto-correlated random process (Markov process) and an independent process (white ... ...

    Abstract The stochastic properties of baseline noise in HPLC systems with a UV photo-diode array, photo-multiplier and gamma-ray detector were examined by dividing the noise into auto-correlated random process (Markov process) and an independent process (white noise). The present work focused on the effect of the stochastic noise properties on a theoretical estimation of the standard deviation (SD) of area measurements in instrumental analyses. An estimation theory, called FUMI theory (Function of Mutual Information), was taken as an example. A computer simulation of noise was also used. It was shown that the reliability (confidence intervals) of theoretical SD estimates mainly depends on the following factors: the ratio of the white noise and Markov process occurring in the baselines; the number of data points used for the estimation; the width of a target peak for which the SD is estimated.
    MeSH term(s) Chromatography, Liquid/methods ; Research Design ; Uncertainty
    Language English
    Publishing date 2007-08-20
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 1483376-1
    ISSN 1348-2246 ; 0910-6340
    ISSN (online) 1348-2246
    ISSN 0910-6340
    DOI 10.2116/analsci.23.1077
    Database MEDical Literature Analysis and Retrieval System OnLINE

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