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Subcellular storage and release mode of the novel (18)F-labeled sympathetic nerve PET tracer LMI1195
BACKGROUND: (18)F-N-[3-bromo-4-(3-fluoro-propoxy)-benzyl]-guanidine ((18)F-LMI1195) is a new class of PET tracer designed for sympathetic nervous imaging of the heart. The favorable image quality with high and specific neural uptake has been previously demonstrated in animals and humans, but intrace...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5801140/ https://www.ncbi.nlm.nih.gov/pubmed/29411169 http://dx.doi.org/10.1186/s13550-018-0365-9 |
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author | Chen, Xinyu Werner, Rudolf A. Lapa, Constantin Nose, Naoko Hirano, Mitsuru Javadi, Mehrbod S. Robinson, Simon Higuchi, Takahiro |
author_facet | Chen, Xinyu Werner, Rudolf A. Lapa, Constantin Nose, Naoko Hirano, Mitsuru Javadi, Mehrbod S. Robinson, Simon Higuchi, Takahiro |
author_sort | Chen, Xinyu |
collection | PubMed |
description | BACKGROUND: (18)F-N-[3-bromo-4-(3-fluoro-propoxy)-benzyl]-guanidine ((18)F-LMI1195) is a new class of PET tracer designed for sympathetic nervous imaging of the heart. The favorable image quality with high and specific neural uptake has been previously demonstrated in animals and humans, but intracellular behavior is not yet fully understood. The aim of the present study is to verify whether it is taken up in storage vesicles and released in company with vesicle turnover. RESULTS: Both vesicle-rich (PC12) and vesicle-poor (SK-N-SH) norepinephrine-expressing cell lines were used for in vitro tracer uptake studies. After 2 h of (18)F-LMI1195 preloading into both cell lines, effects of stimulants for storage vesicle turnover (high concentration KCl (100 mM) or reserpine treatment) were measured at 10, 20, and 30 min. (131)I-meta-iodobenzylguanidine ((131)I-MIBG) served as a reference. Both high concentration KCl and reserpine enhanced (18)F-LMI1195 washout from PC12 cells, while tracer retention remained stable in the SK-N-SH cells. After 30 min of treatment, (18)F-LMI1195 releasing index (percentage of tracer released from cells) from vesicle-rich PC12 cells achieved significant differences compared to cells without treatment condition. In contrast, such effect could not be observed using vesicle-poor SK-N-SH cell lines. Similar tracer kinetics after KCl or reserpine treatment were also observed using (131)I-MIBG. In case of KCl exposure, Ca(2)+-free buffer with the calcium chelator, ethylenediaminetetracetic acid (EDTA), could suppress the tracer washout from PC12 cells. This finding is consistent with the tracer release being mediated by Ca(2)+ influx resulting from membrane depolarization. CONCLUSIONS: Analogous to (131)I-MIBG, the current in vitro tracer uptake study confirmed that (18)F-LMI1195 is also stored in vesicles in PC12 cells and released along with vesicle turnover. Understanding the basic kinetics of (18)F-LMI1195 at a subcellular level is important for the design of clinical imaging protocols and imaging interpretation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13550-018-0365-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5801140 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-58011402018-02-13 Subcellular storage and release mode of the novel (18)F-labeled sympathetic nerve PET tracer LMI1195 Chen, Xinyu Werner, Rudolf A. Lapa, Constantin Nose, Naoko Hirano, Mitsuru Javadi, Mehrbod S. Robinson, Simon Higuchi, Takahiro EJNMMI Res Original Research BACKGROUND: (18)F-N-[3-bromo-4-(3-fluoro-propoxy)-benzyl]-guanidine ((18)F-LMI1195) is a new class of PET tracer designed for sympathetic nervous imaging of the heart. The favorable image quality with high and specific neural uptake has been previously demonstrated in animals and humans, but intracellular behavior is not yet fully understood. The aim of the present study is to verify whether it is taken up in storage vesicles and released in company with vesicle turnover. RESULTS: Both vesicle-rich (PC12) and vesicle-poor (SK-N-SH) norepinephrine-expressing cell lines were used for in vitro tracer uptake studies. After 2 h of (18)F-LMI1195 preloading into both cell lines, effects of stimulants for storage vesicle turnover (high concentration KCl (100 mM) or reserpine treatment) were measured at 10, 20, and 30 min. (131)I-meta-iodobenzylguanidine ((131)I-MIBG) served as a reference. Both high concentration KCl and reserpine enhanced (18)F-LMI1195 washout from PC12 cells, while tracer retention remained stable in the SK-N-SH cells. After 30 min of treatment, (18)F-LMI1195 releasing index (percentage of tracer released from cells) from vesicle-rich PC12 cells achieved significant differences compared to cells without treatment condition. In contrast, such effect could not be observed using vesicle-poor SK-N-SH cell lines. Similar tracer kinetics after KCl or reserpine treatment were also observed using (131)I-MIBG. In case of KCl exposure, Ca(2)+-free buffer with the calcium chelator, ethylenediaminetetracetic acid (EDTA), could suppress the tracer washout from PC12 cells. This finding is consistent with the tracer release being mediated by Ca(2)+ influx resulting from membrane depolarization. CONCLUSIONS: Analogous to (131)I-MIBG, the current in vitro tracer uptake study confirmed that (18)F-LMI1195 is also stored in vesicles in PC12 cells and released along with vesicle turnover. Understanding the basic kinetics of (18)F-LMI1195 at a subcellular level is important for the design of clinical imaging protocols and imaging interpretation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13550-018-0365-9) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2018-02-06 /pmc/articles/PMC5801140/ /pubmed/29411169 http://dx.doi.org/10.1186/s13550-018-0365-9 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Research Chen, Xinyu Werner, Rudolf A. Lapa, Constantin Nose, Naoko Hirano, Mitsuru Javadi, Mehrbod S. Robinson, Simon Higuchi, Takahiro Subcellular storage and release mode of the novel (18)F-labeled sympathetic nerve PET tracer LMI1195 |
title | Subcellular storage and release mode of the novel (18)F-labeled sympathetic nerve PET tracer LMI1195 |
title_full | Subcellular storage and release mode of the novel (18)F-labeled sympathetic nerve PET tracer LMI1195 |
title_fullStr | Subcellular storage and release mode of the novel (18)F-labeled sympathetic nerve PET tracer LMI1195 |
title_full_unstemmed | Subcellular storage and release mode of the novel (18)F-labeled sympathetic nerve PET tracer LMI1195 |
title_short | Subcellular storage and release mode of the novel (18)F-labeled sympathetic nerve PET tracer LMI1195 |
title_sort | subcellular storage and release mode of the novel (18)f-labeled sympathetic nerve pet tracer lmi1195 |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5801140/ https://www.ncbi.nlm.nih.gov/pubmed/29411169 http://dx.doi.org/10.1186/s13550-018-0365-9 |
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