Development and preclinical evaluation of novel fluorinated ammonium salts for PET myocardial perfusion imaging

Abstract We previously presented the radiolabeled ammonium salt [11C]-dimethyl diphenylammonium trifluoromethanesulfonate ([11C]DMDPA) as a potential novel PET-MPI agent. The current study aimed to increase the clinical applicability of PET-MPI by designing and synthesizing fluorinated ammonium salt...

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Autores principales:	Ofer Shamni, Hilbert Grievink, Netanel Kolevzon, Seweryn Krajewski, Lukasz Steczek, Ella Meltzer, Shimon Yitshak, Eyal Mishani, Galith Abourbeh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4b7e4d2ac5ce4724bd71ec1911789a5b
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spelling	oai:doaj.org-article:4b7e4d2ac5ce4724bd71ec1911789a5b2021-12-02T19:16:10ZDevelopment and preclinical evaluation of novel fluorinated ammonium salts for PET myocardial perfusion imaging10.1038/s41598-021-99212-02045-2322https://doaj.org/article/4b7e4d2ac5ce4724bd71ec1911789a5b2021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99212-0https://doaj.org/toc/2045-2322Abstract We previously presented the radiolabeled ammonium salt [11C]-dimethyl diphenylammonium trifluoromethanesulfonate ([11C]DMDPA) as a potential novel PET-MPI agent. The current study aimed to increase the clinical applicability of PET-MPI by designing and synthesizing fluorinated ammonium salt derivatives. Four fluorinated DMDPA derivatives and two quinolinium salt analogs were radiolabeled. The dynamic distribution in vivo, following injection of each derivative into male SD rats, was evaluated using small-animal dedicated PET/CT. Organ uptake after injection of [18F]fluoroethylquinolinium acetate ([18F]FEtQ) was examined ex vivo. Four fluorinated DMDPA derivatives were synthesized, two were labeled with fluorine-18: [18F]fluoroethyl-methyldiphenylammonium trifluoromethanesulfonate ([18F]FEMDPA) and [18F]fluorobuthyl-methyldiphenylammonium trifluoromethanesulfonate ([18F]FBMDPA). The other two were labeled using carbon-11: [11C]methyl-(3-fluorophenyl)-methylphenylammonium trifluoromethanesulfonate ([11C]3-F-DMDPA) and [11C]methyl-(4-fluorophenyl)-methylphenylammonium trifluoromethanesulfonate ([11C]4-F-DMDPA). All four DMDPA derivatives exhibited significantly lower heart/liver radioactivity uptake ratios (0.6, 0.4, 0.7 and 0.6, respectively) compared to that of [11C]DMDPA (1.2). Conversely, the two radiolabeled quinolinium salt derivatives, [11C]methylquinolinium iodide ([11C]MeQ) and [18F]FEtQ demonstrated improved heart/liver ratios (2.0 and 1.3, respectively) with clear visualization of the left ventricle myocardium. Renal clearance was the major route of elimination. Among the fluorinated quaternary ammonium salts tested, [18F]FEtQ yielded the best images. Further studies are in progress to elucidate the underlying mechanism of its cardiac uptake.Ofer ShamniHilbert GrievinkNetanel KolevzonSeweryn KrajewskiLukasz SteczekElla MeltzerShimon YitshakEyal MishaniGalith AbourbehNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ofer Shamni Hilbert Grievink Netanel Kolevzon Seweryn Krajewski Lukasz Steczek Ella Meltzer Shimon Yitshak Eyal Mishani Galith Abourbeh Development and preclinical evaluation of novel fluorinated ammonium salts for PET myocardial perfusion imaging
description	Abstract We previously presented the radiolabeled ammonium salt [11C]-dimethyl diphenylammonium trifluoromethanesulfonate ([11C]DMDPA) as a potential novel PET-MPI agent. The current study aimed to increase the clinical applicability of PET-MPI by designing and synthesizing fluorinated ammonium salt derivatives. Four fluorinated DMDPA derivatives and two quinolinium salt analogs were radiolabeled. The dynamic distribution in vivo, following injection of each derivative into male SD rats, was evaluated using small-animal dedicated PET/CT. Organ uptake after injection of [18F]fluoroethylquinolinium acetate ([18F]FEtQ) was examined ex vivo. Four fluorinated DMDPA derivatives were synthesized, two were labeled with fluorine-18: [18F]fluoroethyl-methyldiphenylammonium trifluoromethanesulfonate ([18F]FEMDPA) and [18F]fluorobuthyl-methyldiphenylammonium trifluoromethanesulfonate ([18F]FBMDPA). The other two were labeled using carbon-11: [11C]methyl-(3-fluorophenyl)-methylphenylammonium trifluoromethanesulfonate ([11C]3-F-DMDPA) and [11C]methyl-(4-fluorophenyl)-methylphenylammonium trifluoromethanesulfonate ([11C]4-F-DMDPA). All four DMDPA derivatives exhibited significantly lower heart/liver radioactivity uptake ratios (0.6, 0.4, 0.7 and 0.6, respectively) compared to that of [11C]DMDPA (1.2). Conversely, the two radiolabeled quinolinium salt derivatives, [11C]methylquinolinium iodide ([11C]MeQ) and [18F]FEtQ demonstrated improved heart/liver ratios (2.0 and 1.3, respectively) with clear visualization of the left ventricle myocardium. Renal clearance was the major route of elimination. Among the fluorinated quaternary ammonium salts tested, [18F]FEtQ yielded the best images. Further studies are in progress to elucidate the underlying mechanism of its cardiac uptake.
format	article
author	Ofer Shamni Hilbert Grievink Netanel Kolevzon Seweryn Krajewski Lukasz Steczek Ella Meltzer Shimon Yitshak Eyal Mishani Galith Abourbeh
author_facet	Ofer Shamni Hilbert Grievink Netanel Kolevzon Seweryn Krajewski Lukasz Steczek Ella Meltzer Shimon Yitshak Eyal Mishani Galith Abourbeh
author_sort	Ofer Shamni
title	Development and preclinical evaluation of novel fluorinated ammonium salts for PET myocardial perfusion imaging
title_short	Development and preclinical evaluation of novel fluorinated ammonium salts for PET myocardial perfusion imaging
title_full	Development and preclinical evaluation of novel fluorinated ammonium salts for PET myocardial perfusion imaging
title_fullStr	Development and preclinical evaluation of novel fluorinated ammonium salts for PET myocardial perfusion imaging
title_full_unstemmed	Development and preclinical evaluation of novel fluorinated ammonium salts for PET myocardial perfusion imaging
title_sort	development and preclinical evaluation of novel fluorinated ammonium salts for pet myocardial perfusion imaging
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4b7e4d2ac5ce4724bd71ec1911789a5b
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_version_	1718376968324382720

Development and preclinical evaluation of novel fluorinated ammonium salts for PET myocardial perfusion imaging

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