Characterization of 5-(2-18F-fluoroethoxy)-L-tryptophan for PET imaging of the pancreas [version 2; referees: 2 approved]

Purpose: In diabetes, pancreatic beta cell mass declines significantly prior to onset of fasting hyperglycemia. This decline may be due to endoplasmic reticulum (ER) stress, and the system L amino acid transporter LAT1 may be a biomarker of this process. In this study, we used 5-(2-18F-fluoroethoxy)...
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Autor*in:	Ahmed Abbas [verfasserIn] Christine Beamish [verfasserIn] Rebecca McGirr [verfasserIn] John Demarco [verfasserIn] Neil Cockburn [verfasserIn] Dawid Krokowski [verfasserIn] Ting-Yim Lee [verfasserIn] Michael Kovacs [verfasserIn] Maria Hatzoglou [verfasserIn] Savita Dhanvantari [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2016

Schlagwörter:	Diabetes & Obesity Methods for Diagnostic & Therapeutic Studies Pancreas

Übergeordnetes Werk:	In: F1000Research - F1000 Research Ltd, 2013, 5(2016)
Übergeordnetes Werk:	volume:5 ; year:2016

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.12688/f1000research.9129.2

Katalog-ID:	DOAJ039278654

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spelling	10.12688/f1000research.9129.2 doi (DE-627)DOAJ039278654 (DE-599)DOAJef83fe1d58304e96ac0556ef92ea30d6 DE-627 ger DE-627 rakwb eng Ahmed Abbas verfasserin aut Characterization of 5-(2-18F-fluoroethoxy)-L-tryptophan for PET imaging of the pancreas [version 2; referees: 2 approved] 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose: In diabetes, pancreatic beta cell mass declines significantly prior to onset of fasting hyperglycemia. This decline may be due to endoplasmic reticulum (ER) stress, and the system L amino acid transporter LAT1 may be a biomarker of this process. In this study, we used 5-(2-18F-fluoroethoxy)-L-tryptophan (18F-L-FEHTP) to target LAT1 as a potential biomarker of beta cell function in diabetes. Procedures: Uptake of 18F-L-FEHTP was determined in wild-type C57BL/6 mice by ex vivo biodistribution. Both dynamic and static positron emission tomography (PET) images were acquired in wild-type and Akita mice, a model of ER stress-induced diabetes, as well as in mice treated with streptozotocin (STZ). LAT1 expression in both groups of mice was evaluated by immunofluorescence microscopy. Results: Uptake of 18F-L-FEHTP was highest in the pancreas, and static PET images showed highly specific pancreatic signal. Time-activity curves showed significantly reduced 18F-L-FEHTP uptake in Akita mice, and LAT1 expression was also reduced. However, mice treated with STZ, in which beta cell mass was reduced by 62%, showed no differences in 18F-L-FEHTP uptake in the pancreas, and there was no significant correlation of 18F-L-FEHTP uptake with beta cell mass. Conclusions: 18F-L-FEHTP is highly specific for the pancreas with little background uptake in kidney or liver. We were able to detect changes in LAT1 in a mouse model of diabetes, but these changes did not correlate with beta cell function or mass. Therefore, 18F-L-FEHTP PET is not a suitable method for the noninvasive imaging of changes in beta cell function during the progression of diabetes. Diabetes & Obesity Methods for Diagnostic & Therapeutic Studies Pancreas Medicine R Science Q Christine Beamish verfasserin aut Rebecca McGirr verfasserin aut John Demarco verfasserin aut Neil Cockburn verfasserin aut Dawid Krokowski verfasserin aut Ting-Yim Lee verfasserin aut Michael Kovacs verfasserin aut Maria Hatzoglou verfasserin aut Savita Dhanvantari verfasserin aut In F1000Research F1000 Research Ltd, 2013 5(2016) (DE-627)735133581 (DE-600)2699932-8 20461402 nnns volume:5 year:2016 https://doi.org/10.12688/f1000research.9129.2 kostenfrei https://doaj.org/article/ef83fe1d58304e96ac0556ef92ea30d6 kostenfrei https://f1000research.com/articles/5-1851/v2 kostenfrei https://doaj.org/toc/2046-1402 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2016
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allfieldsSound	10.12688/f1000research.9129.2 doi (DE-627)DOAJ039278654 (DE-599)DOAJef83fe1d58304e96ac0556ef92ea30d6 DE-627 ger DE-627 rakwb eng Ahmed Abbas verfasserin aut Characterization of 5-(2-18F-fluoroethoxy)-L-tryptophan for PET imaging of the pancreas [version 2; referees: 2 approved] 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose: In diabetes, pancreatic beta cell mass declines significantly prior to onset of fasting hyperglycemia. This decline may be due to endoplasmic reticulum (ER) stress, and the system L amino acid transporter LAT1 may be a biomarker of this process. In this study, we used 5-(2-18F-fluoroethoxy)-L-tryptophan (18F-L-FEHTP) to target LAT1 as a potential biomarker of beta cell function in diabetes. Procedures: Uptake of 18F-L-FEHTP was determined in wild-type C57BL/6 mice by ex vivo biodistribution. Both dynamic and static positron emission tomography (PET) images were acquired in wild-type and Akita mice, a model of ER stress-induced diabetes, as well as in mice treated with streptozotocin (STZ). LAT1 expression in both groups of mice was evaluated by immunofluorescence microscopy. Results: Uptake of 18F-L-FEHTP was highest in the pancreas, and static PET images showed highly specific pancreatic signal. Time-activity curves showed significantly reduced 18F-L-FEHTP uptake in Akita mice, and LAT1 expression was also reduced. However, mice treated with STZ, in which beta cell mass was reduced by 62%, showed no differences in 18F-L-FEHTP uptake in the pancreas, and there was no significant correlation of 18F-L-FEHTP uptake with beta cell mass. Conclusions: 18F-L-FEHTP is highly specific for the pancreas with little background uptake in kidney or liver. We were able to detect changes in LAT1 in a mouse model of diabetes, but these changes did not correlate with beta cell function or mass. Therefore, 18F-L-FEHTP PET is not a suitable method for the noninvasive imaging of changes in beta cell function during the progression of diabetes. Diabetes & Obesity Methods for Diagnostic & Therapeutic Studies Pancreas Medicine R Science Q Christine Beamish verfasserin aut Rebecca McGirr verfasserin aut John Demarco verfasserin aut Neil Cockburn verfasserin aut Dawid Krokowski verfasserin aut Ting-Yim Lee verfasserin aut Michael Kovacs verfasserin aut Maria Hatzoglou verfasserin aut Savita Dhanvantari verfasserin aut In F1000Research F1000 Research Ltd, 2013 5(2016) (DE-627)735133581 (DE-600)2699932-8 20461402 nnns volume:5 year:2016 https://doi.org/10.12688/f1000research.9129.2 kostenfrei https://doaj.org/article/ef83fe1d58304e96ac0556ef92ea30d6 kostenfrei https://f1000research.com/articles/5-1851/v2 kostenfrei https://doaj.org/toc/2046-1402 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2016
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author	Ahmed Abbas
spellingShingle	Ahmed Abbas misc Diabetes & Obesity misc Methods for Diagnostic & Therapeutic Studies misc Pancreas misc Medicine misc R misc Science misc Q Characterization of 5-(2-18F-fluoroethoxy)-L-tryptophan for PET imaging of the pancreas [version 2; referees: 2 approved]
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topic_title	Characterization of 5-(2-18F-fluoroethoxy)-L-tryptophan for PET imaging of the pancreas [version 2; referees: 2 approved] Diabetes & Obesity Methods for Diagnostic & Therapeutic Studies Pancreas
topic	misc Diabetes & Obesity misc Methods for Diagnostic & Therapeutic Studies misc Pancreas misc Medicine misc R misc Science misc Q
topic_unstemmed	misc Diabetes & Obesity misc Methods for Diagnostic & Therapeutic Studies misc Pancreas misc Medicine misc R misc Science misc Q
topic_browse	misc Diabetes & Obesity misc Methods for Diagnostic & Therapeutic Studies misc Pancreas misc Medicine misc R misc Science misc Q
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title	Characterization of 5-(2-18F-fluoroethoxy)-L-tryptophan for PET imaging of the pancreas [version 2; referees: 2 approved]
ctrlnum	(DE-627)DOAJ039278654 (DE-599)DOAJef83fe1d58304e96ac0556ef92ea30d6
title_full	Characterization of 5-(2-18F-fluoroethoxy)-L-tryptophan for PET imaging of the pancreas [version 2; referees: 2 approved]
author_sort	Ahmed Abbas
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author_browse	Ahmed Abbas Christine Beamish Rebecca McGirr John Demarco Neil Cockburn Dawid Krokowski Ting-Yim Lee Michael Kovacs Maria Hatzoglou Savita Dhanvantari
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doi_str_mv	10.12688/f1000research.9129.2
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title_sort	characterization of 5-(2-18f-fluoroethoxy)-l-tryptophan for pet imaging of the pancreas [version 2; referees: 2 approved]
title_auth	Characterization of 5-(2-18F-fluoroethoxy)-L-tryptophan for PET imaging of the pancreas [version 2; referees: 2 approved]
abstract	Purpose: In diabetes, pancreatic beta cell mass declines significantly prior to onset of fasting hyperglycemia. This decline may be due to endoplasmic reticulum (ER) stress, and the system L amino acid transporter LAT1 may be a biomarker of this process. In this study, we used 5-(2-18F-fluoroethoxy)-L-tryptophan (18F-L-FEHTP) to target LAT1 as a potential biomarker of beta cell function in diabetes. Procedures: Uptake of 18F-L-FEHTP was determined in wild-type C57BL/6 mice by ex vivo biodistribution. Both dynamic and static positron emission tomography (PET) images were acquired in wild-type and Akita mice, a model of ER stress-induced diabetes, as well as in mice treated with streptozotocin (STZ). LAT1 expression in both groups of mice was evaluated by immunofluorescence microscopy. Results: Uptake of 18F-L-FEHTP was highest in the pancreas, and static PET images showed highly specific pancreatic signal. Time-activity curves showed significantly reduced 18F-L-FEHTP uptake in Akita mice, and LAT1 expression was also reduced. However, mice treated with STZ, in which beta cell mass was reduced by 62%, showed no differences in 18F-L-FEHTP uptake in the pancreas, and there was no significant correlation of 18F-L-FEHTP uptake with beta cell mass. Conclusions: 18F-L-FEHTP is highly specific for the pancreas with little background uptake in kidney or liver. We were able to detect changes in LAT1 in a mouse model of diabetes, but these changes did not correlate with beta cell function or mass. Therefore, 18F-L-FEHTP PET is not a suitable method for the noninvasive imaging of changes in beta cell function during the progression of diabetes.
abstractGer	Purpose: In diabetes, pancreatic beta cell mass declines significantly prior to onset of fasting hyperglycemia. This decline may be due to endoplasmic reticulum (ER) stress, and the system L amino acid transporter LAT1 may be a biomarker of this process. In this study, we used 5-(2-18F-fluoroethoxy)-L-tryptophan (18F-L-FEHTP) to target LAT1 as a potential biomarker of beta cell function in diabetes. Procedures: Uptake of 18F-L-FEHTP was determined in wild-type C57BL/6 mice by ex vivo biodistribution. Both dynamic and static positron emission tomography (PET) images were acquired in wild-type and Akita mice, a model of ER stress-induced diabetes, as well as in mice treated with streptozotocin (STZ). LAT1 expression in both groups of mice was evaluated by immunofluorescence microscopy. Results: Uptake of 18F-L-FEHTP was highest in the pancreas, and static PET images showed highly specific pancreatic signal. Time-activity curves showed significantly reduced 18F-L-FEHTP uptake in Akita mice, and LAT1 expression was also reduced. However, mice treated with STZ, in which beta cell mass was reduced by 62%, showed no differences in 18F-L-FEHTP uptake in the pancreas, and there was no significant correlation of 18F-L-FEHTP uptake with beta cell mass. Conclusions: 18F-L-FEHTP is highly specific for the pancreas with little background uptake in kidney or liver. We were able to detect changes in LAT1 in a mouse model of diabetes, but these changes did not correlate with beta cell function or mass. Therefore, 18F-L-FEHTP PET is not a suitable method for the noninvasive imaging of changes in beta cell function during the progression of diabetes.
abstract_unstemmed	Purpose: In diabetes, pancreatic beta cell mass declines significantly prior to onset of fasting hyperglycemia. This decline may be due to endoplasmic reticulum (ER) stress, and the system L amino acid transporter LAT1 may be a biomarker of this process. In this study, we used 5-(2-18F-fluoroethoxy)-L-tryptophan (18F-L-FEHTP) to target LAT1 as a potential biomarker of beta cell function in diabetes. Procedures: Uptake of 18F-L-FEHTP was determined in wild-type C57BL/6 mice by ex vivo biodistribution. Both dynamic and static positron emission tomography (PET) images were acquired in wild-type and Akita mice, a model of ER stress-induced diabetes, as well as in mice treated with streptozotocin (STZ). LAT1 expression in both groups of mice was evaluated by immunofluorescence microscopy. Results: Uptake of 18F-L-FEHTP was highest in the pancreas, and static PET images showed highly specific pancreatic signal. Time-activity curves showed significantly reduced 18F-L-FEHTP uptake in Akita mice, and LAT1 expression was also reduced. However, mice treated with STZ, in which beta cell mass was reduced by 62%, showed no differences in 18F-L-FEHTP uptake in the pancreas, and there was no significant correlation of 18F-L-FEHTP uptake with beta cell mass. Conclusions: 18F-L-FEHTP is highly specific for the pancreas with little background uptake in kidney or liver. We were able to detect changes in LAT1 in a mouse model of diabetes, but these changes did not correlate with beta cell function or mass. Therefore, 18F-L-FEHTP PET is not a suitable method for the noninvasive imaging of changes in beta cell function during the progression of diabetes.
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title_short	Characterization of 5-(2-18F-fluoroethoxy)-L-tryptophan for PET imaging of the pancreas [version 2; referees: 2 approved]
url	https://doi.org/10.12688/f1000research.9129.2 https://doaj.org/article/ef83fe1d58304e96ac0556ef92ea30d6 https://f1000research.com/articles/5-1851/v2 https://doaj.org/toc/2046-1402
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author2	Christine Beamish Rebecca McGirr John Demarco Neil Cockburn Dawid Krokowski Ting-Yim Lee Michael Kovacs Maria Hatzoglou Savita Dhanvantari
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up_date	2024-07-03T22:33:39.561Z
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However, mice treated with STZ, in which beta cell mass was reduced by 62%, showed no differences in 18F-L-FEHTP uptake in the pancreas, and there was no significant correlation of 18F-L-FEHTP uptake with beta cell mass. Conclusions: 18F-L-FEHTP is highly specific for the pancreas with little background uptake in kidney or liver. We were able to detect changes in LAT1 in a mouse model of diabetes, but these changes did not correlate with beta cell function or mass. 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Characterization of 5-(2-18F-fluoroethoxy)-L-tryptophan for PET imaging of the pancreas [version 2; referees: 2 approved]

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