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@ARTICLE{Oliveira:878040,
author = {Oliveira, Dennis and Stegmayr, Carina and Heinzel,
Alexander and Ermert, Johannes and Neumaier, Bernd and Shah,
N. Jon and Mottaghy, Felix M. and Langen, Karl-Josef and
Willuweit, Antje},
title = {{H}igh uptake of 68{G}a-{PSMA} and 18{F}-{DCFP}y{L} in the
peritumoral area of rat gliomas due to activated astrocytes},
journal = {EJNMMI Research},
volume = {10},
number = {1},
issn = {2191-219X},
address = {Heidelberg},
publisher = {Springer},
reportid = {FZJ-2020-02596},
pages = {55},
year = {2020},
abstract = {BackgroundRecent studies reported on high uptake of the
PSMA ligands [68Ga]HBED-CC (68Ga-PSMA) and 18F-DCFPyL in
cerebral gliomas. This study explores the regional uptake
and cellular targets of 68Ga-PSMA and 18F-DCFPyL in three
different rat glioma models.MethodsF98, 9 L, or U87 rat
gliomas were implanted into the brains of 38 rats. After
13 days of tumor growth, 68Ga-PSMA (n = 21) or 18F-DCFPyL
(n = 17) was injected intravenously, and animals were
sacrificed 40 min later. Five animals for each tracer and
tumor model were additionally investigated by micro-PET at
20–40 min post injection. Cryosections of the tumor
bearing brains were analyzed by ex vivo autoradiography and
immunofluorescence staining for blood vessels, microglia,
astrocytes, and presence of PSMA. Blood-brain barrier (BBB)
permeability was tested by coinjection of Evans blue dye
(EBD). 68Ga-PSMA uptake after restoration of BBB integrity
by treatment with dexamethasone (Dex) was evaluated in four
animals with U87 gliomas. Competition experiments using the
PSMA-receptor inhibitor 2-(phosphonomethyl)pentane-1,5-dioic
acid (PMPA) were performed for both tracers in two animals
each.ResultsAutoradiography demonstrated a strong 68Ga-PSMA
and 18F-DCFPyL binding in the peritumoral area and moderate
binding in the center of the tumors. PMPA administration led
to complete inhibition of 68Ga-PSMA and 18F-DCFPyL binding
in the peritumoral region. Restoration of BBB by Dex
treatment reduced EBD extravasation but 68Ga-PSMA binding
remained unchanged. Expression of activated microglia
(CD11b) was low in the intra- and peritumoral area but GFAP
staining revealed strong activation of astrocytes in
congruency to the tracer binding in the peritumoral area.
All tumors were visualized in micro PET, showing a lower
tumor/brain contrast with 68Ga-PSMA than with
18F-DCFPyL.ConclusionsHigh uptake of 68Ga-PSMA and
18F-DCFPyL in the peritumoral area of all glioma models is
presumably caused by activated astrocytes. This may
represent a limitation for the clinical application of PSMA
ligands in gliomas.},
cin = {INM-4 / INM-11 / JARA-BRAIN / INM-5},
ddc = {610},
cid = {I:(DE-Juel1)INM-4-20090406 / I:(DE-Juel1)INM-11-20170113 /
$I:(DE-82)080010_20140620$ / I:(DE-Juel1)INM-5-20090406},
pnm = {573 - Neuroimaging (POF3-573)},
pid = {G:(DE-HGF)POF3-573},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32451793},
UT = {WOS:000535370300001},
doi = {10.1186/s13550-020-00642-0},
url = {https://juser.fz-juelich.de/record/878040},
}