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DOI： 10.1016/j.bmc.2019.115189

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We have designed (S)-(5-(azetidin-2-ylmethoxy)pyridine-3-yl)methyl cyclopentadienyltricarbonyl technetium carboxylate ([99mTc]CPTT–A–E)with high affinity for nicotinic acetylcholine receptors (nAChRs)using (2(S)-azetidinylmethoxy)-pyridine (A-85380)as the lead compound to develop a Tc-99m-cyclopentadienyltricarbonyl-technetium (99mTc)-labeled nAChR imaging probe. Because technetium does not contain a stable isotope, cyclopentadienyltricarbonyl rhenium (CPTR)was synthesized by coordinating rhenium, which is a homologous element having the same coordination structure as technetium. Further, the binding affinity to nAChR was evaluated. CPTR–A–E exhibited a high binding affinity to nAChR (Ki = 0.55 nM). Through the radiosynthesis of [99mTc]CPTT–A–E, an objective compound could be obtained with a radiochemical yield of 33% and a radiochemical purity of greater than 97%. In vitro autoradiographic study of the brain exhibited that the local nAChR density strongly correlated with the amount of [99mTc]CPTT–A–E that was accumulated in each region of interest. Further, the in vivo evaluation of biodistribution revealed a higher accumulation of [99mTc]CPTT–A–E in the thalamus (characterized by the high nAChR density)when compared with that in the cerebellum (characterized by the low nAChR density). Although additional studies will be necessary to improve the uptake of [99mTc]CPTT–A–E to the brain, [99mTc]CPTT–A–E met the basic requirements for nAChR imaging.

DOI： 10.1016/j.bmc.2019.04.030

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DOI： 10.1007/s11307-018-1253-4

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：IOP Publishing  

DOI： 10.1088/1361-6463/aaff44

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DOI： 10.7567/1347-4065/aae8e9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japan Institute of Heterocyclic Chemistry  

Novel aminobenzopyranoxanthene spiroethers (ABPX-SEs) based on the spirocyclization of the hydroxymethyl group were synthesized from ABPX spirolactones (ABPX-SLs). The addition of an acid induces a ring-opening reaction to yield two colored monocationic and dicationic spiro-ring species of ABPX. The acid-stimulus responsiveness of the ABPX-SEs is lower than that of ABPX-SLs in polar organic solvents. In addition, the ABPX-SEs exhibit stepwise structural changes of the three equilibrium species at acidic pH, although rapid conversion from the spirolactone to dicationic species occurs in the case of ABPX-SLs.

DOI： 10.3987/com-18-s(f)66

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Many zinc (Zn) complexes have been developed as promising oral antidiabetic agents. In vitro assays using adipocytes have demonstrated that the coordination structures of Zn complexes affect the uptake of Zn into cells and have insulinomimetic activities, for which moderate stability of Zn complexes is vital. The complexation of Zn plays a major role improving its bioavailability. However, investigation of the speciation changes of Zn complexes after oral administration is lacking. A dual radiolabeling approach was applied in order to investigate the speciation of bis(5-chloro-7-iodo-8-quinolinolato)zinc complex [Zn(Cq)2], which exhibits the antidiabetic activity in diabetic mice. In the present study, 65Zn- and 131I-labeled [Zn(Cq)2] were synthesized, and their biodistribution were analyzed after an oral administration using both invasive conventional assays and noninvasive gamma-ray emission imaging (GREI), a novel nuclear medicine imaging modality that enables analysis of multiple radionuclides simultaneously. The GREI experiments visualized the behavior of 65Zn and [131I]Cq from the stomach to large intestine and through the small intestine; most of the administered Zn was transported together with clioquinol (5-chloro-7-iodo-8-quinolinol) (Cq). Higher accumulation of 65Zn for [Zn(Cq)2] than ZnCl2 suggests that the Zn associated with Cq was highly absorbed by the intestinal tract. In particular, the molar ratio of administered iodine to Zn decreased during the distribution processes, indicating the dissociation of most [Zn(Cq)2] complexes. In conclusion, the present study successfully evaluated the speciation changes of orally administered [Zn(Cq)2] using the dual radiolabeling method.

DOI： 10.1248/bpb.b16-00945

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<p>The spirolactone form of aminobenzopyranoxanthenes (ABPXs) exhibited dual solvatochromic and nanoaggregate fluorescence. This intriguing dual fluorescence presented a new detection principle for naked-eye visualisation and quantification of water in tetrahydrofuran.</p>

DOI： 10.1039/c6cp06808a

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DOI： 10.1016/j.crad.2016.04.017

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Low-temperature plasma (LTP) treatment promotes blood clot formation by stimulation of the both platelet aggregation and coagulation factors. However, the appearance of a membrane-like structure in clots after the treatment is controversial. Based on our previous report that demonstrated characteristics of the form of coagulation of serum proteins induced by LTP treatment, we sought to determine whether treatment with two plasma instruments, namely BPC-HP1 and PN-110/120TPG, formed clots only from red blood cells (RBCs). LTP treatment with each device formed clots from whole blood, whereas LTP treatment with BPC-HP1 formed clots in phosphate-buffered saline (PBS) containing 2 × 10(9)/mL RBCs. Light microscopic analysis results showed that hemolysis formed clots consisting of materials with membrane-like structures from both whole blood and PBS-suspended RBCs. Moreover, electron microscopic analysis results showed a monotonous material with high electron density in the formed clots, presenting a membrane-like structure. Hemolysis disappeared with the decrease in the current through the targets contacting with the plasma flare and clot formation ceased. Taken together, our results and those of earlier studies present two types of blood clot formation, namely presence or absence of hemolysis capability depending on the current through the targets.

DOI： 10.1016/j.abb.2016.03.023

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DOI： 10.1016/j.nucmedbio.2016.02.007

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Pharmaceutical Society of Japan  

Molecular imaging is a newly emerging field aimed at advancing our understanding of biology and medicine through the noninvasive in vivo investigation of cellular molecular events involved in normal and pathologic processes. In this field, researchers and/or clinicians are combining modern tools of molecular and cell biology with state of the art technology in order to noninvasively image living subjects. Various imaging modalities such as optics (fluorescence and luminescence), nuclear magnetic resonance imaging, ultrasound, and radiation are being used to visually capture and study molecular and cellular events in living organisms. Among these modalities, nuclear medical molecular imaging uses radionuclides [i.e., positron emission tomography (PET) and single-photon emission computed tomography (SPECT)], and has characteristic properties that allow researchers and/or clinicians to obtain functional images of living subjects with high sensitivity. Translational molecular imaging, a research step between animal experiments and the clinical setting, has been successful when using nuclear medical molecular imaging. This approach leads to better methods for studying biological processes, as well as for diagnosing and managing diseases. In this review, two topics associated with our research on nuclear medical molecular imaging are summarized: (1) the development of a nuclear medical molecular imaging probe that targets cerebral nicotinic acetylcholine receptors (nAChRs), and the translational molecular imaging research conducted using this nAChR imaging probe; and (2) the development of oxygen-dependent degradable nuclear medical molecular imaging probes that target hypoxia-inducible factor-1-active tumor microenvironments.

DOI： 10.1248/yakushi.15-00279

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Various types of zinc (Zn) complexes have been developed as promising antidiabetic agents in recent years. However, the pharmacological action of Zn complex is not elucidated because the biodistribution of the complex in a living organism has not been studied. Nuclear medicine imaging is superior technology for the noninvasive analysis of the temporal distribution of drug candidates in living organisms. Gamma-ray emission imaging (GREI), which was developed by our laboratory as a novel molecular imaging modality, was adopted to visualize various γ-ray-emitting radionuclides that are not detected by conventional imaging techniques such as positron emission tomography and single-photon emission computed tomography. Therefore, we applied GREI to a biodistribution assay of Zn complexes. In the present study, 65Zn was produced in the natCu(p,n) reaction in an azimuthal varying field cyclotron for the GREI experiment. The distribution was then noninvasively visualized using GREI after the intravenous administration of a 65Zn-labeled di(1-oxy-2-pyridinethiolato)zinc [Zn(opt)2], ZnCl2, and di(l-histidinato)zinc. The GREI images were validated using conventional invasive assays. This novel study showed that GREI is a powerful tool for the biodistribution analysis of antidiabetic Zn complexes in a living organism. In addition, accumulation of 65Zn in the cardiac blood pool was observed for [Zn(opt)2], which exhibits potent antidiabetic activity. These results suggest that the slow elimination of Zn from the blood is correlated to the antidiabetic activity of [Zn(opt)2].

DOI： 10.1016/j.bbrep.2015.12.004

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<p>The stability of Cu²⁺–ATCUN complexes under physiologically relevant conditions is enhanced by inserting bulky and hydrophobic residues at positions 1 and 2 of the ATCUN peptide.</p>

DOI： 10.1039/c6dt01387b

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The objective of this study is to determine whether there is a pathway different from the natural blood coagulation process involved in the plasma-induced activation of platelets and coagulation factors. Plasma treatment of bleeding wounds generated glomerular structures, which could be detected in high-magnification scanning electron microscopy images, and plasma flares produced aggregation on the surface of solutions containing bovine serum albumin, ovalbumin (OVA), or similar protein material. Ultramicroscopic analysis of the plasma-generated aggregation of OVA indicated a possible mechanism to explain the particle formation and fusion as a monotonous solid appearance. This study suggests that plasma coagulation involves aggregations of materials in blood in addition to the activation of platelets and coagulation factors by plasma treatment.

DOI： 10.1002/ppap.201500132

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The objective of this study is to examine the invasiveness of hemostasis by non-thermal plasma (NTP) compared with hemostasis by thermal coagulation (TC). The inflammation recovery process after hemostasis by TC and NTP was compared by using histological methods and nuclear medical molecular imaging. The necrotic areas in the NTP group disappeared after 5 days, whereas they remained 15 days after hemostasis in the TC group. The accumulation of 2-deoxy-2-[F-18] fluoro-D-glucopyranose (F-18-FDG), which reflects the existence of inflammatory cells, was higher in the TC group than in the NTP group on day 15. Thus, this study indicates that hemostasis by NTP is less inflammatory than TC. This report is the first to evaluate inflammation that occurred after hemostasis with medical devices noninvasively.

DOI： 10.1002/ppap.201500099

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<title>Abstract</title>
<sec>
<title>Objective</title>
Positron emission tomography (PET)/computed tomography (CT) using ⁶⁸Ga-labeled 1,4,7,10-tetraazacyclododecane-<italic>N</italic>,<italic>N</italic>′,<italic>N</italic>″,<italic>N</italic>‴-tetraacetic acid-<sc>d</sc>-Phe¹-Tyr³-octreotide (DOTATOC) has been used to detect neuroendocrine tumors (NETs). The purpose of this study was to investigate the clinical efficacy of DOTATOC-PET/CT for detecting clinically suspected NETs when conventional imaging modalities were negative or inconclusive, in terms of additional value.


</sec>
<sec>
<title>Methods</title>
A total of 46 patients were analyzed retrospectively. Among them, 14 patients underwent a DOTATOC-PET/CT scan for detecting unknown primary tumors after histopathological confirmation of a NET at metastatic sites (group A): 7 patients for detecting metastasis or recurrence after surgery for NET because of their high hormone levels but with no recurrence detected by other imaging modalities (group B); the remaining 25 patients for detecting suspected NETs because their hormone levels were high with no history of histopathologically proven NET (group C). Additional information was assessed, according to each situation.


</sec>
<sec>
<title>Results</title>
In group A, unknown primary tumors were suspected by DOTATOC-PET/CT in 8 of 14 patients (gastrointestinal/pancreatic NET in 7 patients, prostatic cancer in 1 patient), but prostatic cancer was not confirmed by histopathology (i.e., false positive). In group B, DOTATOC-PET/CT depicted lesions in six of seven patients, including nodal metastasis (<italic>n</italic> = 5) and liver metastasis (<italic>n</italic> = 1). In group C, DOTATOC-PET/CT did not demonstrate any abnormal foci except in one case of pancreatic NET. Additional information was obtained in 50, 86, and 4 % of cases, in groups A, B, and C, respectively.


</sec>
<sec>
<title>Conclusions</title>
DOTATOC-PET/CT was useful for detecting NETs, especially when recurrence or metastases were suspected because of high hormone levels after surgery for a NET. It is unlikely, however, that additional information can be acquired in patients with no history of NET simply based on high hormone levels.


</sec>

DOI： 10.1007/s12149-015-0973-7

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Mechanochromic organic molecules (MOMs) that exhibit a large difference of fluorescence wavelength between two states have important potential applications, but few such compounds are known. Here, we report a new MOM, cis-ABPX01(0), which shows switchable near-IR and blue fluorescence responses. Detailed spectrophotometric and single-crystal X-ray analyses revealed that the near-IR fluorescence is attributable to fluorescence from slip-stacked dimeric structures in crystals, while the blue fluorescence is attributable to fluorescence from the monomer. Switching between the two is achieved by dynamic structural interconversion between the two molecular packing arrangements in response to mechanical grinding and solvent vapor-fuming.

DOI： 10.1021/jacs.5b00877

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DOI： 10.1007/s11307-014-0769-5

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DOI： 10.1371/journal.pone.0109866

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DOI： 10.1016/j.bbrc.2014.02.086

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Hindawi Limited  

Because tumor cells grow rapidly and randomly, hypoxic regions arise from the lack of oxygen supply in solid tumors. Hypoxic regions in tumors are known to be resistant to chemotherapy and radiotherapy. Hypoxia-inducible factor-1 (HIF-1) expressed in hypoxic regions regulates the expression of genes related to tumor growth, angiogenesis, metastasis, and therapy resistance. Thus, imaging of HIF-1-active regions in tumors is of great interest. HIF-1 activity is regulated by the expression and degradation of its<italic>α</italic>subunit (HIF-1<italic>α</italic>), which is degraded in the proteasome under normoxic conditions, but escapes degradation under hypoxic conditions, allowing it to activate transcription of HIF-1-target genes. Therefore, to image HIF-1-active regions, HIF-1-dependent reporter systems and injectable probes that are degraded in a manner similar to HIF-1<italic>α</italic>have been recently developed and used in preclinical studies. However, no probe currently used in clinical practice directly assesses HIF-1 activity. Whether the accumulation of¹⁸F-FDG or¹⁸F-FMISO can be utilized as an index of HIF-1 activity has been investigated in clinical studies. In this review, the current status of HIF-1 imaging in preclinical and clinical studies is discussed.

DOI： 10.1155/2014/165461

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DOI： 10.1371/journal.pone.0081191

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DOI： 10.1007/s11307-013-0647-6

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DOI： 10.1021/jm300251n

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Pharmaceutical Society of Japan  

In solid tumors, hypoxic regions arise because of an imbalance between oxygen supply and consumption. The transcription factor hypoxia-inducible factor-1 (HIF-1), which is overexpressed in hypoxic regions, was recently reported to be a master transcriptional activator of various genes (such as those involved in glucose metabolism, vascularization, invasion, and metastasis) related to malignant phenotypes. Therefore, the development of techniques for the noninvasive detection of HIF-1-active hypoxic tumor cells is of great interest. Although various modalities are used for molecular imaging in vivo, nuclear medical imaging, which can give information about organ functions, plays a central quantitative role in molecular imaging. However, because radioactive probes become attenuated due to the nuclide-specific half-life, an appropriate probe design and/or imaging method is required to obtain a high-contrasted image within a limited time. My colleagues and I have developed a probe and a method for the rapid detection of HIF-1-active hypoxic regions in tumors. Because the α subunit of HIF-1 (HIF-1α) controls the transcriptional activity of HIF-1 and is unique in that its degradation is regulated by the oxygen partial pressure, we first developed a fusion protein probe that is degraded similarly as HIF-1α. Then, to control the biodistribution of radioactivity, we utilized a "pretargeting method" that uses a combination of the fusion protein and a small-molecule radioactive probe that can bind to the protein and is rapidly cleared from the blood. Rapid and high-contrast imaging of HIF-1-active tumors can be achieved with this pretargeting method.<br>

DOI： 10.1248/yakushi.132.595

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DOI： 10.1016/j.jconrel.2012.01.016

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DOI： 10.1021/jm201513c

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DOI： 10.1021/ml200230e

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<italic>Purpose</italic>. We aimed to clearly visualize heterogeneous distribution of hypoxia-inducible factor 1<italic>α</italic>(HIF) activity in tumor tissues<italic>in vivo</italic>.<italic>Methods</italic>. We synthesized of¹²⁵I-IPOS, a¹²⁵I labeled chimeric protein probe, that would visualize HIF activity. The biodistribution of¹²⁵I-IPOS in FM3A tumor-bearing mice was evaluated. Then, the intratumoral localization of this probe was observed by autoradiography, and it was compared with histopathological findings. The distribution of¹²⁵I-IPOS in tumors was imaged by a small animal SPECT/CT scanner. The obtained<italic>in vivo</italic>SPECT-CT fusion images were compared with<italic>ex vivo</italic>images of excised tumors. Fusion imaging with MRI was also examined.<italic>Results</italic>.¹²⁵I-IPOS well accumulated in FM3A tumors. The intratumoral distribution of¹²⁵I-IPOS by autoradiography was quite heterogeneous, and it partially overlapped with that of pimonidazole. High-resolution SPECT-CT fusion images successfully demonstrated the heterogeneity of¹²⁵I-IPOS distribution inside tumors. SPECT-MRI fusion images could give more detailed information about the intratumoral distribution of¹²⁵I-IPOS.<italic>Conclusion</italic>. High-resolution SPECT images successfully demonstrated heterogeneous intratumoral distribution of¹²⁵I-IPOS. SPECT-CT fusion images, more favorably SPECT-MRI fusion images, would be useful to understand the features of heterogeneous intratumoral expression of HIF activity<italic>in vivo</italic>.

DOI： 10.1155/2012/262741

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DOI： 10.1111/j.1349-7006.2011.02057.x

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DOI： 10.1007/s11307-010-0418-6

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DOI： 10.1002/syn.20819

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DOI： 10.1016/j.nima.2010.03.085

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DOI： 10.1007/s00259-010-1467-4

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DOI： 10.1111/j.1476-5381.2009.00613.x

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We have developed an electron-tracking Compton camera (ETCC) for new medical imaging device. Conventional gamma camera, PET and SPECT, have the problem of energy limitation. This problem is one of the major problems for this study. However, our ETCC has a wide energy dynamic range (200-1300 keV). Also ETCC have the wide field of view because ETCC does not need a collimator and does not need to catch two gamma rays which produced by the annihilation process. In this paper, we show the results of imaging result of the 3-D which have imaged only one direction using one head camera. And we have developed the two-head ETCC. Two-head ETCC have a good efficiency and spatial resolution. © 2010 IEEE.

DOI： 10.1109/NSSMIC.2010.5874313

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We have developed an electron-tracking Compton camera (ETCC) for new medical imaging device. Conventional gamma camera, PET and SPECT, have the problem of energy limitation. This problem is one of the major problems for this study. However, our ETCC has a wide energy dynamic range (200-1300 keV). Also ETCC have the wide field of view because ETCC does not need a collimator and does not need to catch two gamma rays which produced by the annihilation process.
In this paper, we show the results of imaging result of the 3-D which have imaged only one direction using one head camera. And we have developed the two-head ETCC. Two-head ETCC have a good efficiency and spatial resolution.

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We examined exendin(9-39), an antagonist of glucagon-like peptide-1 (GLP-1) receptor (GLP-1R), as a potential probe for imaging of pancreatic beta-cells. To evaluate in vitro receptor specificity, binding assay was performed using dispersed mouse islet cells. Binding assay showed competitive inhibition of [(125)I]BH-exendin(9-39) binding by non-radioactive exendin(9-39). To assess in vivo selectivity, the biodistribution was evaluated by intravenous administration of [(125)I]BH-exendin(9-39) to mice. Radioactivity of harvested pancreas reached highest levels at 60 and 120min among organs examined except lung. Pre-administration of excess non-radioactive exendin(9-39) remarkably and specifically blocked the radioactivity of pancreas. After [(125)I]BH-exendin(9-39) injection into transgenic mice with pancreatic beta-cells expressing GFP, fluorescent and radioactive signals of sections of pancreas were evaluated with an image analyzer. Imaging analysis showed that the fluorescent GFP signals and the radioactive signals were correspondingly located. Thus, the GLP-1R antagonist exendin(9-39) may serve as a useful probe for pancreatic beta-cell imaging.

DOI： 10.1016/j.bbrc.2009.09.014

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Hypoxia-inducible factor-1 (HIF-1) plays an important role in malignant tumor progression and in the development of resistance to radiotherapy. We designed a novel fusion protein (PTD-ODD-SAV [POS]) consisting of a protein transduction domain (PTD), streptavidin (SAV), and a portion of the oxygen-dependent degradation domain (ODD) of HIF-1 alpha that confers the same oxygen-dependent regulation as HIF-1 alpha on POS. (3-(123/125)I-iodobenzoyl) norbiotinamide ((123/125)I-IBB) was conjugated to the SAV moiety of POS to synthesize (123/125)I-IBB-labeled POS ((123/125)I-IPOS). The purpose of this study was to evaluate the feasibility of (123)I-IPOS as an imaging probe for HIF-1-active tumor hypoxia. Methods: After a 24-h incubation of (125)I-IPOS with various tumor cell lines under either normoxic (20% O(2)) or hypoxic (0.1% O(2)) conditions, the intracellular radioactivity was investigated. Then, the biodistribution of (123/125)I-IPOS was examined with tumor-implanted mice, and an in vivo imaging study was performed. The tumoral accumulation of (125)I-IPOS was compared with HIF-1 activity using the mice carrying tumors with the HIF-1-dependent luciferase reporter gene. Furthermore, the intratumoral localization of (125)I-IPOS was examined by the autoradiographic study, and then the same slide was subjected to immunostaining for pimonidazole, which is the hypoxic marker. Results: The ratios of radioactivity in hypoxic cells to that in normoxic cells were more than 2. These results indicate incorporation of (125)I-IPOS into these cells and degradation of (125)I-IPOS by normoxic tumor cells. In the biodistribution study, (125)I-IPOS accumulated in the tumor (1.4 +/- 0.3 percentage injected dose per gram) 24 h after administration. At that time, (125)I-IPOS showed high tumor-to-blood and tumor-to-muscle ratios (5.1 +/- 0.3 and 14.0 +/- 3.9, respectively). The tumors were clearly visualized by in vivo imaging 24 h after (123)I-IPOS injection (tumor-to-muscle ratio was 9.6). The tumoral accumulation of (125)I-IPOS correlated with HIF-1 activity (R = 0.71, P &lt; 0.05), and its intratumoral distribution coincided with the hypoxic regions. Conclusion: (123)I-IPOS is a potential probe for the imaging of HIF-1 activity in tumors. Given the role of HIF-1 in tumor biology, its detection may be considered an indicator of aggressive cancer phenotypes.

DOI： 10.2967/jnumed.108.061119

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DOI： 10.1016/j.nucmedbio.2008.11.007

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We have developed the Electron tracking Compton Camera (ETCC) with reconstructing the 3-D tracks of the scattered electron in Compton process for both gamma-ray astronomy and medical imaging [1-3]. By measuring both the directions and energies of a recoil gamma ray and a scattered electron, the direction of the incident gamma ray is determined for an individual photon. Furthermore, a residual measured angle between the recoil electron and scattered gamma ray is powerful for the kinematical background-rejection. For the 3-D tracking of the electrons, the Micro Time Projection Chamber (mu-TPC) was developed, which consists of a new type of the micro pattern gas detector, or a Micro Pixel Gas Chamber (mu-PIC). The ETCC consists of this mu-TPC and the GSO crystal pixel arrays below the (mu) over bar TPC for detecting the recoil gamma rays. The ETCC provided the gamma ray images of point sources between 120keV and similar to 1 MeV with the angular resolution of 6 degree (FWHM) at 511 keV of F-18 ion, respectively. Also the angle of the scattered electron was measured with the resolution of similar to 80 degree.
Two mobile ETCCs with 10cm-cube TPC for small animal and 30cm-cube TPC for human body, are now being operated for Medical Imaging test. We have studied the imaging performances using both phantoms and small animals (rats and mice) for conventional radioisotopes of I-131 and F-18-FDG. In particular, new ETCC with LaBr3 pixel scintillator provides good images similar to SPECT for I-131 and human PET for 511keV, respectively, where a clear concentration to tumors in a mouse is observed The 30cm-cube ETCC can get an image for I m-size length objects in one measurement. Thus, we have carried out several comparisons of our images with those of SPECT and PET. Multi-tracer image using I-131 and FDG for small animal and the image for higher energy gamma ray above 511keV for plants using Mn-54 have been carried out successfully. Also several new biomarkers and new radio nuclides were examined to verify the merits of ETCC for medical imaging.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Society of Nuclear Medicine  

DOI： 10.2967/jnumed.107.050260

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

DOI： 10.1109/nssmic.2008.4774145

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.brainres.2007.10.107

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.nucmedbio.2007.11.006

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Society of Nuclear Medicine  

DOI： 10.2967/jnumed.107.043471

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.jns.2007.02.014

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

DOI： 10.1109/nssmic.2007.4436859

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

DOI： 10.1109/nssmic.2006.356499

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s00259-005-0017-y

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Other Link： http://link.springer.com/article/10.1007/s00259-005-0017-y/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.nucmedbio.2006.03.006

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.nucmedbio.2005.06.013

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Pharmacological Society  

In this study, we investigated the effect of vesicular zinc on ischemic neuronal injury. In cultured neurons, addition of a low concentration (under 100 μM) of zinc inhibited both glutamate-induced calcium influx and neuronal death. In contrast, a higher concentration (over 150 μM) of zinc decreased neuronal viability, although calcium influx was inhibited. These results indicate that zinc exhibits biphasic effects depending on its concentration. Furthermore, in cultured neurons, co-addition of glutamate and CaEDTA, which binds extra-cellular zinc, increased glutamate-induced calcium influx and aggravated the neurotoxicity of glutamate. In a rat transient middle cerebral artery occlusion (MCAO) model, the infarction volume, which is related to the neurotoxicity of glutamate, increased rapidly on the intracerebral ventricular injection of CaEDTA 30 min prior to occlusion. These results suggest that zinc released from synaptic vesicles may provide a protective effect against ischemic neuronal injury.<br>

DOI： 10.1254/jphs.fp0050805

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Other Link： https://jlc.jst.go.jp/DN/JALC/00273496883?from=CiNii

Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

We have developed the Electron tracking Compton Camera (ETCC) with reconstructing the 3-D tracks of the scattered electron in Compton process in the range from sub-MeV to several MeV for both gamma-ray astronomy and medical imaging [1,2]. By measuring both the directions and energies of a recoil gamma ray and a scattered electron, the direction of the incident gamma ray is determined for each individual photon. Furthermore, a residual measured angle between the recoil electron and scattered gamma ray is powerful for the kinematical background-rejection. For the 3-D tracking of the electrons, the Micro Time Projection Chamber (mu-TPC) was developed, which consists of a new type of the micro pattern gas detector, or a Micro Pixel Gas Chamber (mu-PIC) [2,3,4]. The ETCC consists of this mu-TPC (10cm cube) and the 6x6x3mm GSO crystal pixel arrays with a flat panel photo-multiplier surrounding the base and side of the mu-TPC for detecting the recoil gamma rays. The ETCC provided the gamma ray images of point sources between 120keV and similar to 1 MeV with the angular resolution of 6 degree and 5 degree (FWHM) at 364keV of (131)Iodine and 511keV of F-18 ion, respectively. Also the angle of the scattered electron was measured with the resolution of similar to 80 degree, by which most backgrounds were removed by the kinematical constraint.A mobile ETCC for medical imaging, which is fabricated in a 1m cubic box, has been tested since October 2005. Here we present the imaging performances using both a phantom and a rat.

DOI： 10.1109/NSSMIC.2006.353834

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SOC NUCLEAR MEDICINE INC  

Neuronal nicotinic acetylcholine receptors (nAChRs) are widely distributed in the human brain, especially the alpha(4)beta(2) subtype of nAChR. The cholinergic systems have roles in various neurophysiologic functions, such as learning, memory, and cognition, whereas normal aging and neurodegenerative diseases have been associated with changes in nAChRs. Recently, 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5IA) has been synthesized as a radioligand for imaging nAChRs with SPECT. I-123-5IA shows higher affinity toward the nAChR alpha(4)beta(2) subtype, enhanced receptor subtype selectivity, good safety, and low nonspecific binding. Methods: In this study, a SPECT quantitative study of human nAChRs binding with I-123-5IA was conducted in healthy volunteers. An arterial input function was obtained for each subject and a 2-compartment model was used to determine the kinetic parameters of I-123-5IA using data from a 6-h scan. The distribution volume (V-T) (mL/mL), which is related to the number of unoccupied binding sites in the brain, was calculated and values were compared with results of a graphical analysis (Logan plot, V-LG). Results: Analysis of the unmetabolized compound showed a high parent fraction of I-123-5IA in plasma. The results from the 2-compartment model analysis showed high VT values for the thalamus; moderate values for the brain stem, cerebellum, and basal ganglia; and low values for the cortical regions. Good agreement was observed between VT values and results of autoradiographic experiments done in vitro for nAChR density in human brain. A high correlation index was observed between distribution volumes from model and graphical analyses. Conclusion: Our results indicated that I-123-5IA SPECT is suitable for the quantification of nAChRs in human brain.

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/bf02984473

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Other Link： http://link.springer.com/article/10.1007/BF02984473/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SOC NUCLEAR MEDICINE INC  

Central nicotinic acetylcholine receptors (nAChRs) represent major neurotransmitter receptors responsible for various brain functions, and changes in the density of nAChRs have recently been reported in several neurodegenerative diseases. Visualization of nAChRs in human brain has thus been of great interest, and the development of radiopharmaceuticals for the imaging and quantitative assessment of central nAChRs has been desired. In this study, we synthesized 5-(11)C-methyl-3-(2-(S)-azetidinylmethoxy)pyridine (5MA), a derivative of 3-(2-(S)-azetidinylmethoxy)pyridine (A-85380) (11)C-methylated at position 5 of the pyridyl fragment, and evaluated its potential for investigating central nAChRs by PET. Methods: (11)C-5MA was synthi by the incorporation of (11)C-methyl iodide into 5-butylstannyl A-85380, using a Pd-catalyzed coupling reaction. The affinity of 5MA for central nAChRs was measured by displacement of (-)-(3)H-cytisine from binding sites in rat cortical membranes. The biodistribution of (11)C-5MA was determined with mice. PET studies were performed on rhesus monkeys with a high-resolotion PET scanner for animals. Results: The overall synthesis time was 60 min from the end of radionudide production, and the radiochemical yield, after purification by high-performance liquid chromatography, was 30%. The radiochemical purity of the product was &gt;99%, with a specific radioactivity of &gt;36 GBq/mumol. In vitro receptor-binding assays demonstrated that 5MA has a high, selective binding affinity for nAChRs, being approximately 1.5-fold higher than that of A-85380, 3.5-fold higher than that of (-)-cytisine, and 10-fold higher than that of (-)-nicotine. The distribution studies in mice showed that the brain uptake of (11)C-5MA was profound. Regional cerebral distribution studies in mice demonstrated that the accumulation of (11)C-5MA was consistent with the density of nAChRs, with the highest uptake observed in the thalamus, a moderate uptake in the cortex and striatum, and the lowest uptake in the cerebellum. Furthermore, preinjection of nAChR-binding ligands, (-)nicotine and (-)-cytisine, reduced the uptake of (11)C-5MA in brain regions of high uptake in the untreated experiment. PET imaging studies with (11)C-5MA in rhesus monkeys demonstrated clear images consistent with the distribution of nAChRs in the brain. Conclusion: These results suggest that (11)C-5MA is a potential PET radiopharmaceutical for nuclear medical studies of nAChRs in the brain.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.ics.2003.12.067

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/bf02996300

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Other Link： http://link.springer.com/article/10.1007/BF02996300/fulltext.html

Total pages：xi, 303p   Language：Japanese

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Total pages：711  

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Total pages：316  

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Total pages：xvi, 427p, 図版 [14] p   Language：Japanese

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Publisher：Wiley  

DOI： 10.1002/ppap.201570043

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Language：English   Publisher：Hindawi Limited  

DOI： 10.1155/2015/365418

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Other Link： http://orcid.org/0000-0002-1691-7302

Authorship：Lead author   Language：Japanese   Publishing type：Research paper, summary (national, other academic conference)  

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Authorship：Lead author   Language：English   Publishing type：Research paper, summary (international conference)  

DOI： 10.1155/2014/165461

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Language：Japanese   Publishing type：Research paper, summary (national, other academic conference)   Publisher：(公社)日本薬学会  

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Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)   Publisher：寺田国際事務所先端医療技術研究所  

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Other Link： http://search.jamas.or.jp/link/ui/2014270749

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER DIABETES ASSOC  

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Language：Japanese  

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Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

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Authorship：Lead author   Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

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Language：Japanese   Publisher：寺田国際事務所先端医療技術研究所  

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Language：English   Publisher：IEEE  

We have developed an electron-tracking Compton camera (ETCC) for new imaging reagents study. Energy limitation of gamma camera is major problem for this study. However, our ETCC has a wide energy dynamic range (200-1300 keV). In this paper, we show the results of imaging reagent stud) as follows: (1) F-18-FDG (511 keV) and 1-131-MIBG (364 keV) simultaneous imaging for double clinical tracer imaging, (2) Zn-65-porphyrin (1116 keV) imaging for high energy gamma-ray imaging and, (3) middle size animal imaging (rabbit). Also we studied the improvement for the camera system.

DOI： 10.1109/NSSMIC.2009.5401649

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Language：Japanese   Publishing type：Research paper, summary (national, other academic conference)  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：SPRINGER  

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Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY-LISS  

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Authorship：Lead author   Language：Japanese   Publishing type：Book review, literature introduction, etc.  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：SOC NUCLEAR MEDICINE INC  

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Event date： 2011.9

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Event date： 2009.11

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