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Subcellular storage and release mode of the novel \(^{18}\)F-labeled sympathetic nerve PET tracer LMI1195

Please always quote using this URN: urn:nbn:de:bvb:20-opus-167081
  • 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)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, 18F-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 131I-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 \(^{131}\)F-LMI1195 is also stored in vesicles in PC12 cells and released along with vesicle turnover. Understanding the basic kinetics of \(^{18}\)FLMI1195 at a subcellular level is important for the design of clinical imaging protocols and imaging interpretation.show moreshow less

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Metadaten
Author: Xinyu Chen, Rudolf A. Werner, Constantin Lapa, Naoko Nose, Mitsuru Hirano, Mehrbod S. Javadi, Simon Robinson, Takahiro Higuchi
URN:urn:nbn:de:bvb:20-opus-167081
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Nuklearmedizin
Language:English
Parent Title (English):EJNMMI Research
ISSN:2191-219X
Year of Completion:2018
Volume:8
Issue:12
Source:EJNMMI Research (2018) 8:12 https://doi.org/10.1186/s13550-018-0365-9
DOI:https://doi.org/10.1186/s13550-018-0365-9
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=29411169
Sonstige beteiligte Institutionen:Johns Hopkins School of Medicine
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
GND Keyword:Positronen-Emissions-Tomografie
Tag:18F-LMI1195; heart failure; phaeochromocytoma; positron emission tomography; storage vesicle turnover; sympathetic nervous system
Release Date:2018/08/13
EU-Project number / Contract (GA) number:701983
OpenAIRE:OpenAIRE
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2018
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International