Biodistribution and PET Imaging of pharmacokinetics of manganese in mice using Manganese-52
Abstract
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 injectionmore »
- Authors:
-
[1];
- Washington Univ., St. Louis, MO (United States). School of Medicine and Mallinckrodt Inst. of Radiology and Dept. of Biomedical Engineering
- Washington Univ., St. Louis, MO (United States). School of Medicine and Mallinckrodt Inst. of Radiology
- Washington Univ., St. Louis, MO (United States). School of Medicine and Mallinckrodt Inst. of Radiology and Dept. of Physics
- Washington Univ., St. Louis, MO (United States). School of Medicine and Mallinckrodt Inst. of Radiology and Dept. of Biomedical Engineering; Univ. of Alabama, Birmingham, AL (United States). Dept. of Radiology
- Publication Date:
- Research Org.:
- Washington Univ., St. Louis, MO (United States); Univ. of California, Los Angeles, CA (United States)
- Sponsoring Org.:
- USDOE National Nuclear Security Administration (NNSA), Office of Defense Nuclear Nonproliferation; Four Star Finishing, St. Louis, MO (United States)
- OSTI Identifier:
- 1347275
- Alternate Identifier(s):
- OSTI ID: 1425831
- Grant/Contract Number:
- NA0000979
- Resource Type:
- Published Article
- Journal Name:
- PLoS ONE
- Additional Journal Information:
- Journal Name: PLoS ONE Journal Volume: 12 Journal Issue: 3; Journal ID: ISSN 1932-6203
- Publisher:
- Public Library of Science
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES; manganese; inhalation; intravenous injections; pancreas; thyroid; chromium; kidneys; positron emission tomography
Citation Formats
Wooten, A. Lake, Aweda, Tolulope A., Lewis, Benjamin C., Gross, Rebecca B., and Lapi, Suzanne E. Biodistribution and PET Imaging of pharmacokinetics of manganese in mice using Manganese-52. United States: N. p., 2017.
Web. doi:10.1371/journal.pone.0174351.
Wooten, A. Lake, Aweda, Tolulope A., Lewis, Benjamin C., Gross, Rebecca B., & Lapi, Suzanne E. Biodistribution and PET Imaging of pharmacokinetics of manganese in mice using Manganese-52. United States. https://doi.org/10.1371/journal.pone.0174351
Wooten, A. Lake, Aweda, Tolulope A., Lewis, Benjamin C., Gross, Rebecca B., and Lapi, Suzanne E. Fri .
"Biodistribution and PET Imaging of pharmacokinetics of manganese in mice using Manganese-52". United States. https://doi.org/10.1371/journal.pone.0174351.
@article{osti_1347275,
title = {Biodistribution and PET Imaging of pharmacokinetics of manganese in mice using Manganese-52},
author = {Wooten, A. Lake and Aweda, Tolulope A. and Lewis, Benjamin C. and Gross, Rebecca B. and Lapi, Suzanne E.},
abstractNote = {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. In conclusion, 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.},
doi = {10.1371/journal.pone.0174351},
journal = {PLoS ONE},
number = 3,
volume = 12,
place = {United States},
year = {Fri Mar 17 00:00:00 EDT 2017},
month = {Fri Mar 17 00:00:00 EDT 2017}
}
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