Multitracer Screening: Brain Delivery of Trace Elements by Eight Different Administration Methods

Kanayama, Yousuke; Tsuji, T; Enomoto, Shuichi; Amano, Ryohei

doi:10.1007/s10534-005-4775-6

Cited by 17 publications

(10 citation statements)

References 21 publications

(13 reference statements)

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“…Kanayama, et al [65] administered to mice by eight different routes a solution containing sixteen different radiotracers, mostly transition metals, and, for most administration routes, 54 Mn(II) had higher brain uptake than most of the other tracers. In several other studies, rodents received radiomanganese by carotid injection or continuous in situ brain perfusion brain.…”

Section: Discussionmentioning

confidence: 99%

Biodistribution and PET Imaging of pharmacokinetics of manganese in mice using Manganese-52

et al. 2017

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Manganese is essential to life, and humans typically absorb sufficient quantities of this element from a normal healthy diet; however, chronic, elevated ingestion or inhalation of manganese can be neurotoxic, potentially leading to manganism. Although imaging of large amounts of accumulated Mn(II) is possible by MRI, quantitative measurement of the biodistribution of manganese, particularly at the trace level, can be challenging. In this study, we produced the positron-emitting radionuclide 52Mn (t1/2 = 5.6 d) by proton bombardment (Ep<15 MeV) of chromium metal, followed by solid-phase isolation by cation-exchange chromatography. An aqueous solution of [52Mn]MnCl2 was nebulized into a closed chamber with openings through which mice inhaled the aerosol, and a separate cohort of mice received intravenous (IV) injections of [52Mn]MnCl2. Ex vivo biodistribution was performed at 1 h and 1 d post-injection/inhalation (p.i.). In both trials, we observed uptake in lungs and thyroid at 1 d p.i. Manganese is known to cross the blood-brain barrier, as confirmed in our studies following IV injection (0.86%ID/g, 1 d p.i.) and following inhalation of aerosol, (0.31%ID/g, 1 d p.i.). Uptake in salivary gland and pancreas were observed at 1 d p.i. (0.5 and 0.8%ID/g), but to a much greater degree from IV injection (6.8 and 10%ID/g). In a separate study, mice received IV injection of an imaging dose of [52Mn]MnCl2, followed by in vivo imaging by positron emission tomography (PET) and ex vivo biodistribution. The results from this study supported many of the results from the biodistribution-only studies. In this work, we have confirmed results in the literature and contributed new results for the biodistribution of inhaled radiomanganese for several organs. Our results could serve as supporting information for environmental and occupational regulations, for designing PET studies utilizing 52Mn, and/or for predicting the biodistribution of manganese-based MR contrast agents.

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Section: Discussionmentioning

confidence: 99%

Biodistribution and PET Imaging of pharmacokinetics of manganese in mice using Manganese-52

et al. 2017

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“…Studies in rats demonstrate that Mn is rapidly transported along the evolutionarily conserved olfactory pathway and is present within the olfactory bulb 8–48 h after exposure. It is believed that the trigeminal nerve may also play a role in delivering Mn from the nasal cavity to the brain [38, 42, 43]. …”

Section: Absorption Distribution and Eliminationmentioning

confidence: 99%

Manganese Toxicity Upon Overexposure: a Decade in Review

O’Neal

Zheng

2015

Curr Envir Health Rpt

631

340

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Exposure to manganese (Mn) causes clinical signs and symptoms resembling, but not identical to, Parkinson’s disease. Since our last review on this subject in 2004, the past decade has been a thriving period in the history of Mn research. This report provides a comprehensive review on new knowledge gained in the Mn research field. Emerging data suggest that beyond traditionally recognized occupational manganism, Mn exposures and the ensuing toxicities occur in a variety of environmental settings, nutritional sources, contaminated foods, infant formulas, and water, soil, and air with natural or man-made contaminations. Upon fast absorption into the body via oral and inhalation exposures, Mn has a relatively short half-life in blood, yet fairly long half-lives in tissues. Recent data suggest Mn accumulates substantially in bone, with a half-life of about 8–9 years expected in human bones. Mn toxicity has been associated with dopaminergic dysfunction by recent neurochemical analyses and synchrotron X-ray fluorescent imaging studies. Evidence from humans indicates that individual factors such as age, gender, ethnicity, genetics, and pre-existing medical conditions can have profound impacts on Mn toxicities. In addition to body fluid-based biomarkers, new approaches in searching biomarkers of Mn exposure include Mn levels in toenails, non-invasive measurement of Mn in bone, and functional alteration assessments. Comments and recommendations are also provided with regard to the diagnosis of Mn intoxication and clinical intervention. Finally, several hot and promising research areas in the next decade are discussed.

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“…What are the target molecules and biological roles of Zn signaling? Another question is how to specifically monitor and visualize intracellular free Zn in vivo with high resolution; this will require the use of chemical compounds [92], multitracer detection devices [144], and two-photon and X-ray fluorescence microscopy [145, 146]. The development of drugs for Zn-related diseases is another emerging avenue of study.…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

Zinc homeostasis and signaling in health and diseases

et al. 2011

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The essential trace element zinc (Zn) is widely required in cellular functions, and abnormal Zn homeostasis causes a variety of health problems that include growth retardation, immunodeficiency, hypogonadism, and neuronal and sensory dysfunctions. Zn homeostasis is regulated through Zn transporters, permeable channels, and metallothioneins. Recent studies highlight Zn’s dynamic activity and its role as a signaling mediator. Zn acts as an intracellular signaling molecule, capable of communicating between cells, converting extracellular stimuli to intracellular signals, and controlling intracellular events. We have proposed that intracellular Zn signaling falls into two classes, early and late Zn signaling. This review addresses recent findings regarding Zn signaling and its role in physiological processes and pathogenesis.

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Multitracer Screening: Brain Delivery of Trace Elements by Eight Different Administration Methods

Cited by 17 publications

References 21 publications

Biodistribution and PET Imaging of pharmacokinetics of manganese in mice using Manganese-52

Biodistribution and PET Imaging of pharmacokinetics of manganese in mice using Manganese-52

Manganese Toxicity Upon Overexposure: a Decade in Review

Zinc homeostasis and signaling in health and diseases

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