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Introduction: Nicotinic acetylcholine receptors (nAChRs) are of great interest because they are implicated in higher brain functions. Nuclear medical imaging is one of the useful techniques for noninvasive evaluation of physiological and pathological function in living subjects. Recent progress in nuclear medical imaging modalities enables the clear visualization of the organs of small rodents. Thus, translational research using nuclear medical imaging in transgenic mice has become possible and helps to elucidate human disease pathology. However, imaging of α4β2 nAChRs in the mouse brain has not yet been performed. The purpose of this study was to assess the feasibility of single-photon emission computed tomography (SPECT) with 5-[(123)I]iodo-3-[2(S)-azetidinylmethoxy]pyridine ([(123)I]5IA) for evaluating α4β2 nAChR availability in the mouse brain., Methods: A 60-min dynamic SPECT imaging session of α4β2 nAChRs in the mouse brain was performed. The regional distribution of radioactivity in the SPECT images was compared to the density of α4β2 nAChRs measured in an identical mouse. Alteration of nAChR density in the brains of Tg2576 mice was also evaluated., Results: The mouse brain was clearly visualized by [(123)I]5IA-SPECT and probe accumulation was significantly inhibited by pretreatment with (-)-nicotine. The regional distribution of radioactivity in SPECT images showed a significant positive correlation with α4β2 nAChR density measured in an identical mouse brain. Moreover, [(123)I]5IA-SPECT was able to detect the up-regulation of α4β2 nAChRs in the brains of Tg2576 transgenic mice., Conclusions: [(123)I]5IA-SPECT imaging would be a promising tool for evaluating α4β2 nAChR availability in the mouse brain and may be useful in translational research focused on nAChR-related diseases., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A portable mass spectrometer with an electron cyclotron resonance ion source (miniECRIS-MS) was developed. It was used for in situ monitoring of trace amounts of chemical warfare agents (CWAs) in atmospheric air. Instrumental construction and parameters were optimized to realize a fast response, high sensitivity, and a small body size. Three types of CWAs, i.e., phosgene, mustard gas, and hydrogen cyanide were examined to check if the mass spectrometer was able to detect characteristic elements and atomic groups. From the results, it was found that CWAs were effectively ionized in the miniECRIS-MS, and their specific signals could be discerned over the background signals of air. In phosgene, the signals of the 35Cl+ and 37Cl+ ions were clearly observed with high dose-response relationships in the parts-per-billion level, which could lead to the quantitative on-site analysis of CWAs. A parts-per-million level of mustard gas, which was far lower than its lethal dosage (LCt50), was successfully detected with a high signal-stability of the plasma ion source. It was also found that the chemical forms of CWAs ionized in the plasma, i.e., monoatomic ions, fragment ions, and molecular ions, could be detected, thereby enabling the effective identification of the target CWAs. Despite the disadvantages associated with miniaturization, the overall performance (sensitivity and response time) of the miniECRIS-MS in detecting CWAs exceeded those of sector-type ECRIS-MS, showing its potential for on-site detection in the future., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Molecular imaging technology is a powerful tool for the diagnosis of inflammatory bowel disease (IBD) and the efficacy evaluation of various drug therapies for it. However, it is difficult to elucidate directly the relationships between the responsible molecules and IBD using existing probes. Therefore, the development of an alternative probe that is able to elucidate the pathogenic mechanism and provide information on the appropriate guidelines for treatment is earnestly awaited. In this study, we investigated pathognomonic molecules in the intestines of model mice. The accumulation of fluorine-18 fluorodeoxyglucose ((18)F-FDG) in the inflamed area of the intestines of dextran sulfate sodium (DSS)- or indomethacin (IND)-induced IBD model mice was measured by positron emission tomography (PET) and autoradiography to confirm the inflamed area. The results suggested that the inflammation was selectively induced in the colons of mice by the administration of DSS, whereas it was induced mainly in the ilea and the proximal colons of mice by the administration of IND. To explore attractive target molecules for the molecular imaging of IBD, we evaluated the gene expression levels of cytokines and cytokine receptors in the inflamed area of the intestines of both model mice. We found that the expression levels of cytokines and cytokine receptors were significantly increased during the progression of IBD, whereas the expression levels were decreased as the mucosa began to heal. In particular, the expression levels of these molecules had already changed before the symptoms of IBD appeared. In addition, the alterations of cytokine and cytokine receptor expression levels indicated differences in the expression pattern depending on the pathogenic mechanism or the region of inflammation (e.g., TNF-α). Our results suggest that these cytokines or cytokine receptors participate in the pathogenesis of IBD and are valuable biomarkers for the detection of the different circumstances underlying inflammation by the molecular imaging method. Finally, the development of an imaging probe for our target molecules is expected to improve our understanding of the inflammatory conditions of IBD., (Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.)

We developed a detection technology for vapor forms of chemical warfare agents (CWAs) with an element analysis system using an electron cyclotron resonance ion source. After the vapor sample was introduced directly into the ion source, the molecular material was decomposed into elements using electron cyclotron resonance plasma and ionized. The following CWAs and stimulants were examined: diisopropyl fluorophosphonate (DFP), 2-chloroethylethylsulfide (2CEES), cyanogen chloride (CNCl), and hydrogen cyanide (HCN). The type of chemical warfare agents, specifically, whether it was a nerve agent, blister agent, blood agent, or choking agent, could be determined by measuring the quantities of the monatomic ions or CN(+) using mass spectrometry. It was possible to detect gaseous CWAs that could not be detected by a conventional mass spectrometer. The distribution of electron temperature in the plasma could be closely controlled by adjusting the input power of the microwaves used to generate the electron cyclotron resonance plasma, and the target compounds could be detected as molecular ions or fragment ions, enabling identification of the target agents., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The mechanism of cellular entry of cadmium remains unclear. We have previously established cadmium-resistant cells from mouse embryonic cells of metallothionein (MT)-null mice, and demonstrated that the down-regulation of a zinc transporter, Zrt/Irt-related protein (ZIP) 8, was responsible for the reduced cadmium incorporation into cells. In the present study, we developed cadmium-resistant cells (A+70 and B+70) from mouse embryonic cells of MT-expressing wild-type mice. The LC₅₀ values of CdCl₂ for A+70 and B+70 cells were about 200 μM while that of the parental cells was 30 μM. We found that the cadmium resistance of these cells was conferred not only by enhanced expression of MT, but also by a decrease in cadmium accumulation. Since the uptake rates of cadmium into A+70 and B+70 cells were lowered, we determined the expression levels of the metal transporters and channels potentially involved in the cellular uptake of cadmium. We found a down-regulation of multiple transport systems, including ZIP8, divalent metal transporter 1 (DMT1), and α₁ subunits of L-type (Ca(V)1.2) and T-type (Ca(V)3.1) voltage-dependent calcium channels, in A+70 and B+70 cells. Furthermore, A+70 and B+70 cells exhibited cross-resistance to cytotoxicity of MnCl₂, probably due to a marked decrease in manganese uptake in these cells. These results suggest that the suppressed expression of ZIP8 and DMT1, which are known to have affinities for both cadmium and manganese, may be responsible for the reduction in the uptake, and consequently the cytotoxicity, of cadmium and manganese in A+70 and B+70 cells., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Following intranasal administration of radioactive (86)Rb(+) and (201)Tl(+) in mice, we observed this direct transport via the olfactory nerve pathway. The (86)RbCl and (201)TlCl solutions were administered to two groups of mice, the unilateral intranasal and intravenous administration groups. After sacrifice, their heads were divided into the right and left side, which were then subdivided into seven parts; the nasal mucosa and brain regions were separated. Following the unilateral intranasal administration, uptake after 6 h by the olfactory bulb was significantly higher on the ipsilateral side ((86)Rb, 0.7 %dose; (201)Tl, 0.5 %dose) than on the contralateral side ((86)Rb, 0.08 %dose; (201)Tl, 0.15 %dose). Moreover, the (86)Rb and (201)Tl that accumulated in the olfactory bulb were gradually transported to other brain regions of the olfactory tract, the telencephalon and the diencephalon on the side corresponding to the nostril used for administration. Significant differences were observed between the right and left side of the brain regions 6 and 12 h after administration. Further, (201)Tl autoradiography clearly showed striped patterns of dense accumulation, localized in the region around the glomerular layer and granule cell layer of the olfactory bulb and around the olfactory cortex. These results provide clear evidence of axonal transport via the olfactory nerve pathway, from nasal cavity to the olfactory bulb, as well as to the olfactory cortex through the synaptic junctions. The olfactory transport of the (86)Rb(+) and (201)Tl(+) is thought to represent the behavior of K(+) in the olfactory system.

The multitracer technique was applied to the determination of the uptake of trace elements in the lenses of normal and hereditary cataract UPL rats to investigate the transport mechanisms of trace elements during cataract development. Be, Na, Sc, V, Cr, Mn, Fe, Co, Zn, As, Se, Rb, Sr, Y, Zr, Tc, Ru and Rh accumulate in normal and UPL cataract rat lenses. The rates of uptake of trace elements differ among species and also differ between normal and UPL rat lenses. The uptakes of V and Sr are greater in normal rat lenses, while the uptakes of Mn and Co are greater in UPL rat lenses. High concentrations of Zn are transported into normal rat lenses in comparison with other elements. However, the uptake of Se was highest in the lenses of UPL cataract rats. In addition, the difference in Se uptake between the normal and UPL rat lenses was greatest among the tested trace elements. The present study suggests that the transport characteristics of trace elements are different in the lenses of normal and UPL cataract rats. The different transport characteristics of trace elements in the lenses of normal and UPL cataract rats, especially the higher accumulation of Se in UPL rat lenses, may be implicated in cataract development.

The search for radionuclides that can be an index of viability in proliferating cells is important for nuclear medicine diagnosis of brain tumors. On the basis of the finding that 65Zn is preferentially taken up in rat brain tumors, the uptake of various radionuclides was examined in rat brain tumor by using the multitracer technique. Male Fisher rats were intrahippocampally injected with C6 glioma cells. Fourteen days after implantation, the radioactive multitracer solution was injected into the tail vein of tumor-bearing rats. One hour after intravenous injection, the uptake of 65Zn, 83Rb and 54Mn was relatively high in C6 glioma of 15 radionuclides detected, and was much higher than in other brain regions and in the blood. It is likely that rubidium and manganese, in addition to zinc, are preferentially taken up by tumors in the brain.