Influence of blood-brain barrier permeability on O-(2-18F-fluoroethyl)-L-tyrosine uptake in rat gliomas.
OBJECTIVE
O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) is an established tracer for the diagnosis of brain tumors with PET. This study investigates the influence of blood-brain barrier (BBB) permeability on18F-FET uptake in two rat glioma models and one human xenograft model.


METHODS
F98 glioma, 9L gliosarcoma or human U87 glioblastoma cells were implanted into the striatum of 56 Fischer or RNU rats. Thereafter, animals were divided into a control group and a group receiving injections of the glucocorticoid dexamethasone (Dex). After 12-13 days of tumor growth animals received injection of Evans blue dye (EBD) to visualize BBB disturbance and underwent18F-FET PET followed by autoradiography. Time activity curves, standardized uptake values (SUV) and Tumor-to-brain ratios (TBR) of18F-FET uptake [18-61 min post injection (p.i.)] were evaluated using a volume-of-Interest (VOI) analysis. BBB disturbance was quantitatively evaluated by EBD fluorescence. The membrane gaps of blood vessel endothelial tight junctions were measured using electron microscopy to visualize ultrastructural BBB alterations in one untreated and one Dex treated F98 glioma. Data were analyzed by two-way ANOVAs.


RESULTS
In Dex treated animals EBD extravasation was significantly reduced in 9L (P < 0.001) and U87 (P = 0.008) models and showed a trend in F98 models (P = 0.053). In contrast, no significant differences of18F-FET uptake were observed between Dex treated animals and control group except a decrease of the TBR in the 9L tumor model in PET (P < 0.01). Ultrastructural evaluation of tumor blood vessel endothelia revealed significant reduction of the cleft diameter between endothelial cells after Dex treatment in F98 model (P = 0.010).


CONCLUSIONS
Despite a considerable reduction of BBB permeability in rat gliomas after Dex treatment, no relevant changes of18F-FET uptake were noted in this experimental study. Thus,18F-FET uptake in gliomas appears to be widely independent of the permeability of the BBB.
Forschungszentrum Jülich, Institute of Neuroscience and Medicine, D-52425, Jülich, Germany. c.stegmayr@fz-juelich.de.
Carina
C
Stegmayr
Forschungszentrum Jülich, Institute of Neuroscience and Medicine, D-52425, Jülich, Germany.
Ulrike
U
Bandelow
Forschungszentrum Jülich, Institute of Neuroscience and Medicine, D-52425, Jülich, Germany.
Dennis
D
Oliveira
Forschungszentrum Jülich, Institute of Neuroscience and Medicine, D-52425, Jülich, Germany.
Philipp
P
Lohmann
Forschungszentrum Jülich, Institute of Neuroscience and Medicine, D-52425, Jülich, Germany.
Antje
A
Willuweit
Forschungszentrum Jülich, Institute of Neuroscience and Medicine, D-52425, Jülich, Germany.|Department of Nuclear Medicine and Neurology, RWTH/University Hospital Aachen, Aachen, Germany.
Christian
C
Filss
Forschungszentrum Jülich, Institute of Neuroscience and Medicine, D-52425, Jülich, Germany.
Norbert
N
Galldiks
Forschungszentrum Jülich, Institute of Neuroscience and Medicine, D-52425, Jülich, Germany.
Joachim H R
JH
Lübke
Forschungszentrum Jülich, Institute of Neuroscience and Medicine, D-52425, Jülich, Germany.|Department of Nuclear Medicine and Neurology, RWTH/University Hospital Aachen, Aachen, Germany.|Jülich-Aachen Research Alliance (JARA) - Section JARA-Brain, Aachen, Germany.
N Jon
NJ
Shah
Forschungszentrum Jülich, Institute of Neuroscience and Medicine, D-52425, Jülich, Germany.|Department of Nuclear Medicine and Neurology, RWTH/University Hospital Aachen, Aachen, Germany.
Johannes
J
Ermert
Forschungszentrum Jülich, Institute of Neuroscience and Medicine, D-52425, Jülich, Germany. k.j.langen@fz-juelich.de.|Department of Nuclear Medicine and Neurology, RWTH/University Hospital Aachen, Aachen, Germany. k.j.langen@fz-juelich.de.
Karl-Josef
KJ
Langen
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism; D002199:Capillary Permeability; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000009:adverse effects; D005910:Glioma / Q000000981:diagnostic imaging*; D006801:Humans; D008297:Male; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D019108:Tight Junctions / Q000378:metabolism / Q000648:ultrastructure; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D018931:Antineoplastic Agents, Hormonal; D019275:Radiopharmaceuticals; C545932:(18F)fluoroethyltyrosine; D014443:Tyrosine; D003907:Dexamethasone
Blood brain barrier (BBB); Brain tumors; Dexamethasone; O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET); PET