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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},
}