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A side-by-side evaluation of [(18)F]FDOPA enantiomers for non-invasive detection of neuroendocrine tumors by positron emission tomography

Neuroendocrine tumors (NETs) are an extremely heterogenous group of malignancies with variable clinical behavior. Molecular imaging of patients with NETs allows for effective patient stratification and treatment guidance and is crucial in selection of targeted therapies. Positron emission tomography...

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Autores principales: Narayan, Athira, Yan, Yu, Lisok, Ala, Brummet, Mary, Pomper, Martin G., Lesniak, Wojciech G., Dannals, Robert F., Merino, Vanessa F., Azad, Babak Behnam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791383/
https://www.ncbi.nlm.nih.gov/pubmed/31645896
http://dx.doi.org/10.18632/oncotarget.27184
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author Narayan, Athira
Yan, Yu
Lisok, Ala
Brummet, Mary
Pomper, Martin G.
Lesniak, Wojciech G.
Dannals, Robert F.
Merino, Vanessa F.
Azad, Babak Behnam
author_facet Narayan, Athira
Yan, Yu
Lisok, Ala
Brummet, Mary
Pomper, Martin G.
Lesniak, Wojciech G.
Dannals, Robert F.
Merino, Vanessa F.
Azad, Babak Behnam
author_sort Narayan, Athira
collection PubMed
description Neuroendocrine tumors (NETs) are an extremely heterogenous group of malignancies with variable clinical behavior. Molecular imaging of patients with NETs allows for effective patient stratification and treatment guidance and is crucial in selection of targeted therapies. Positron emission tomography (PET) with the radiotracer L-[(18)F]FDOPA is progressively being utilized for non-invasive in vivo visualization of NETs and pancreatic β-cell hyperplasia. While L-[(18)F]FDOPA-PET is a valuable tool for disease detection and management, it also exhibits significant diagnostic limitations owing to its inherent physiological uptake in off-target tissues. We hypothesized that the D-amino acid structural isomer of that clinical tracer, D-[(18)F]FDOPA, may exhibit superior clearance capabilities owing to a reduced in vivo enzymatic recognition and enzyme-mediated metabolism. Here, we report a side-by-side evaluation of D-[(18)F]FDOPA with its counterpart clinical tracer, L-[(18)F]FDOPA, for the non-invasive in vivo detection of NETs. In vitro evaluation in five NET cell lines, including invasive small intestinal neuroendocrine carcinomas (STC-1), insulinomas (TGP52 and TGP61), colorectal adenocarcinomas (COLO-320) and pheochromocytomas (PC12), generally indicated higher overall uptake levels of L-[(18)F]FDOPA, compared to D-[(18)F]FDOPA. While in vivo PET imaging and ex vivo biodistribution studies in PC12, STC-1 and COLO-320 mouse xenografts further supported our in vitro data, they also illustrated lower off-target retention and enhanced clearance of D-[(18)F]FDOPA from healthy tissues. Cumulatively our results indicate the potential diagnostic applications of D-[(18)F]FDOPA for malignancies where the utility of L-[(18)F]FDOPA-PET is limited by the physiological uptake of L-[(18)F]FDOPA, and suggest D-[(18)F]FDOPA as a viable PET imaging tracer for NETs.
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spelling pubmed-67913832019-10-23 A side-by-side evaluation of [(18)F]FDOPA enantiomers for non-invasive detection of neuroendocrine tumors by positron emission tomography Narayan, Athira Yan, Yu Lisok, Ala Brummet, Mary Pomper, Martin G. Lesniak, Wojciech G. Dannals, Robert F. Merino, Vanessa F. Azad, Babak Behnam Oncotarget Research Paper Neuroendocrine tumors (NETs) are an extremely heterogenous group of malignancies with variable clinical behavior. Molecular imaging of patients with NETs allows for effective patient stratification and treatment guidance and is crucial in selection of targeted therapies. Positron emission tomography (PET) with the radiotracer L-[(18)F]FDOPA is progressively being utilized for non-invasive in vivo visualization of NETs and pancreatic β-cell hyperplasia. While L-[(18)F]FDOPA-PET is a valuable tool for disease detection and management, it also exhibits significant diagnostic limitations owing to its inherent physiological uptake in off-target tissues. We hypothesized that the D-amino acid structural isomer of that clinical tracer, D-[(18)F]FDOPA, may exhibit superior clearance capabilities owing to a reduced in vivo enzymatic recognition and enzyme-mediated metabolism. Here, we report a side-by-side evaluation of D-[(18)F]FDOPA with its counterpart clinical tracer, L-[(18)F]FDOPA, for the non-invasive in vivo detection of NETs. In vitro evaluation in five NET cell lines, including invasive small intestinal neuroendocrine carcinomas (STC-1), insulinomas (TGP52 and TGP61), colorectal adenocarcinomas (COLO-320) and pheochromocytomas (PC12), generally indicated higher overall uptake levels of L-[(18)F]FDOPA, compared to D-[(18)F]FDOPA. While in vivo PET imaging and ex vivo biodistribution studies in PC12, STC-1 and COLO-320 mouse xenografts further supported our in vitro data, they also illustrated lower off-target retention and enhanced clearance of D-[(18)F]FDOPA from healthy tissues. Cumulatively our results indicate the potential diagnostic applications of D-[(18)F]FDOPA for malignancies where the utility of L-[(18)F]FDOPA-PET is limited by the physiological uptake of L-[(18)F]FDOPA, and suggest D-[(18)F]FDOPA as a viable PET imaging tracer for NETs. Impact Journals LLC 2019-10-08 /pmc/articles/PMC6791383/ /pubmed/31645896 http://dx.doi.org/10.18632/oncotarget.27184 Text en Copyright: © 2019 Narayan et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Narayan, Athira
Yan, Yu
Lisok, Ala
Brummet, Mary
Pomper, Martin G.
Lesniak, Wojciech G.
Dannals, Robert F.
Merino, Vanessa F.
Azad, Babak Behnam
A side-by-side evaluation of [(18)F]FDOPA enantiomers for non-invasive detection of neuroendocrine tumors by positron emission tomography
title A side-by-side evaluation of [(18)F]FDOPA enantiomers for non-invasive detection of neuroendocrine tumors by positron emission tomography
title_full A side-by-side evaluation of [(18)F]FDOPA enantiomers for non-invasive detection of neuroendocrine tumors by positron emission tomography
title_fullStr A side-by-side evaluation of [(18)F]FDOPA enantiomers for non-invasive detection of neuroendocrine tumors by positron emission tomography
title_full_unstemmed A side-by-side evaluation of [(18)F]FDOPA enantiomers for non-invasive detection of neuroendocrine tumors by positron emission tomography
title_short A side-by-side evaluation of [(18)F]FDOPA enantiomers for non-invasive detection of neuroendocrine tumors by positron emission tomography
title_sort side-by-side evaluation of [(18)f]fdopa enantiomers for non-invasive detection of neuroendocrine tumors by positron emission tomography
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791383/
https://www.ncbi.nlm.nih.gov/pubmed/31645896
http://dx.doi.org/10.18632/oncotarget.27184
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