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[(18)F]FE@SUPPY: a suitable PET tracer for the adenosine A3 receptor? An in vivo study in rodents
PURPOSE: The adenosine A(3) receptor (A3R) is involved in cardiovascular, neurological and tumour-related pathologies and serves as an exceptional pharmaceutical target in the clinical setting. A3R antagonists are considered antiinflammatory, antiallergic and anticancer agents, and to have potential...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349960/ https://www.ncbi.nlm.nih.gov/pubmed/25601336 http://dx.doi.org/10.1007/s00259-014-2976-3 |
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author | Haeusler, Daniela Kuntner, Claudia Nics, Lukas Savli, Markus Zeilinger, Markus Wanek, Thomas Karagiannis, Panagiotis Lanzenberger, Rupert R. Langer, Oliver Shanab, Karem Spreitzer, Helmut Wadsak, Wolfgang Hacker, Marcus Mitterhauser, Markus |
author_facet | Haeusler, Daniela Kuntner, Claudia Nics, Lukas Savli, Markus Zeilinger, Markus Wanek, Thomas Karagiannis, Panagiotis Lanzenberger, Rupert R. Langer, Oliver Shanab, Karem Spreitzer, Helmut Wadsak, Wolfgang Hacker, Marcus Mitterhauser, Markus |
author_sort | Haeusler, Daniela |
collection | PubMed |
description | PURPOSE: The adenosine A(3) receptor (A3R) is involved in cardiovascular, neurological and tumour-related pathologies and serves as an exceptional pharmaceutical target in the clinical setting. A3R antagonists are considered antiinflammatory, antiallergic and anticancer agents, and to have potential for the treatment of asthma, COPD, glaucoma and stroke. Hence, an appropriate A3R PET tracer would be highly beneficial for the diagnosis and therapy monitoring of these diseases. Therefore, in this preclinical in vivo study we evaluated the potential as a PET tracer of the A3R antagonist [(18)F]FE@SUPPY. METHODS: Rats were injected with [(18)F]FE@SUPPY for baseline scans and blocking scans (A3R with MRS1523 or FE@SUPPY, P-gp with tariquidar; three animals each). Additionally, metabolism was studied in plasma and brain. In a preliminary experiment in a mouse xenograft model (mice injected with cells expressing the human A3R; three animals), the animals received [(18)F]FE@SUPPY and [(18)F]FDG. Dynamic PET imaging was performed (60 min in rats, 90 min in xenografted mice). In vitro stability of [(18)F]FE@SUPPY in human and rat plasma was also evaluated. RESULTS: [(18)F]FE@SUPPY showed high uptake in fat-rich regions and low uptake in the brain. Pretreatment with MRS1523 led to a decrease in [(18)F]FE@SUPPY uptake (p = 0.03), and pretreatment with the P-gp inhibitor tariquidar led to a 1.24-fold increase in [(18)F]FE@SUPPY uptake (p = 0.09) in rat brain. There was no significant difference in metabolites in plasma and brain in the treatment groups. However, plasma concentrations of [(18)F]FE@SUPPY were reduced to levels similar to those in rat brain after blocking. In contrast to [(18)F]FDG uptake (p = 0.12), the xenograft model showed significantly increased uptake of [(18)F]FE@SUPPY in the tissue masses from CHO cells expressing the human A3R (p = 0.03). [(18)F]FE@SUPPY was stable in human plasma. CONCLUSION: Selective and significant tracer uptake of [(18)F]FE@SUPPY was found in xenografted mice injected with cells expressing human A3R. This finding supports the strategy of evaluating [(18)F]FE@SUPPY in “humanized animal models”. In conclusion, preclinical evaluation points to the suitability of [(18)F]FE@SUPPY as an A3R PET tracer in humans. |
format | Online Article Text |
id | pubmed-4349960 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-43499602015-03-11 [(18)F]FE@SUPPY: a suitable PET tracer for the adenosine A3 receptor? An in vivo study in rodents Haeusler, Daniela Kuntner, Claudia Nics, Lukas Savli, Markus Zeilinger, Markus Wanek, Thomas Karagiannis, Panagiotis Lanzenberger, Rupert R. Langer, Oliver Shanab, Karem Spreitzer, Helmut Wadsak, Wolfgang Hacker, Marcus Mitterhauser, Markus Eur J Nucl Med Mol Imaging Original Article PURPOSE: The adenosine A(3) receptor (A3R) is involved in cardiovascular, neurological and tumour-related pathologies and serves as an exceptional pharmaceutical target in the clinical setting. A3R antagonists are considered antiinflammatory, antiallergic and anticancer agents, and to have potential for the treatment of asthma, COPD, glaucoma and stroke. Hence, an appropriate A3R PET tracer would be highly beneficial for the diagnosis and therapy monitoring of these diseases. Therefore, in this preclinical in vivo study we evaluated the potential as a PET tracer of the A3R antagonist [(18)F]FE@SUPPY. METHODS: Rats were injected with [(18)F]FE@SUPPY for baseline scans and blocking scans (A3R with MRS1523 or FE@SUPPY, P-gp with tariquidar; three animals each). Additionally, metabolism was studied in plasma and brain. In a preliminary experiment in a mouse xenograft model (mice injected with cells expressing the human A3R; three animals), the animals received [(18)F]FE@SUPPY and [(18)F]FDG. Dynamic PET imaging was performed (60 min in rats, 90 min in xenografted mice). In vitro stability of [(18)F]FE@SUPPY in human and rat plasma was also evaluated. RESULTS: [(18)F]FE@SUPPY showed high uptake in fat-rich regions and low uptake in the brain. Pretreatment with MRS1523 led to a decrease in [(18)F]FE@SUPPY uptake (p = 0.03), and pretreatment with the P-gp inhibitor tariquidar led to a 1.24-fold increase in [(18)F]FE@SUPPY uptake (p = 0.09) in rat brain. There was no significant difference in metabolites in plasma and brain in the treatment groups. However, plasma concentrations of [(18)F]FE@SUPPY were reduced to levels similar to those in rat brain after blocking. In contrast to [(18)F]FDG uptake (p = 0.12), the xenograft model showed significantly increased uptake of [(18)F]FE@SUPPY in the tissue masses from CHO cells expressing the human A3R (p = 0.03). [(18)F]FE@SUPPY was stable in human plasma. CONCLUSION: Selective and significant tracer uptake of [(18)F]FE@SUPPY was found in xenografted mice injected with cells expressing human A3R. This finding supports the strategy of evaluating [(18)F]FE@SUPPY in “humanized animal models”. In conclusion, preclinical evaluation points to the suitability of [(18)F]FE@SUPPY as an A3R PET tracer in humans. Springer Berlin Heidelberg 2015-01-20 2015 /pmc/articles/PMC4349960/ /pubmed/25601336 http://dx.doi.org/10.1007/s00259-014-2976-3 Text en © The Author(s) 2015 https://creativecommons.org/licenses/by/4.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Original Article Haeusler, Daniela Kuntner, Claudia Nics, Lukas Savli, Markus Zeilinger, Markus Wanek, Thomas Karagiannis, Panagiotis Lanzenberger, Rupert R. Langer, Oliver Shanab, Karem Spreitzer, Helmut Wadsak, Wolfgang Hacker, Marcus Mitterhauser, Markus [(18)F]FE@SUPPY: a suitable PET tracer for the adenosine A3 receptor? An in vivo study in rodents |
title | [(18)F]FE@SUPPY: a suitable PET tracer for the adenosine A3 receptor? An in vivo study in rodents |
title_full | [(18)F]FE@SUPPY: a suitable PET tracer for the adenosine A3 receptor? An in vivo study in rodents |
title_fullStr | [(18)F]FE@SUPPY: a suitable PET tracer for the adenosine A3 receptor? An in vivo study in rodents |
title_full_unstemmed | [(18)F]FE@SUPPY: a suitable PET tracer for the adenosine A3 receptor? An in vivo study in rodents |
title_short | [(18)F]FE@SUPPY: a suitable PET tracer for the adenosine A3 receptor? An in vivo study in rodents |
title_sort | [(18)f]fe@suppy: a suitable pet tracer for the adenosine a3 receptor? an in vivo study in rodents |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349960/ https://www.ncbi.nlm.nih.gov/pubmed/25601336 http://dx.doi.org/10.1007/s00259-014-2976-3 |
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