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A side-by-side evaluation of [18F]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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Published in: | Oncotarget 2019-10, Vol.10 (56), p.5731-5744 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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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ISSN: | 1949-2553 1949-2553 |
DOI: | 10.18632/oncotarget.27184 |