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Investigating the Uptake of 68Ga-PSMA and 18F-DCFPyL in Gliomas

25th May 2020

Dennis Oliveira, Carina Stegmayr, Alexander Heinzel, Johannes Ermert, Bernd Neumaier, Nadim Jon Shah, Felix M. Mottaghy, Karl-Josef Langen, Antje Willuweit

PSMA (prostate-specific membrane antigen) is an antigen that is highly expressed on the cell surface of prostate cancer cells. PET imaging can be used to identify PSMA expressing tissues by using ligands such as 68Ga-labelled PSMA inhibitor Glu-NH-CO-NH-Lys(Ahx)-HBED-CC (68Ga-PSMA) and 18F-labelled ligands such as 2-(3-(1-carboxy–5-[(6-[18F]fluoro-pyridine–3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid (18F-DCFPyL). PET imaging with PSMA ligands is particularly successful for the diagnosis and staging of prostate cancer .

In addition to being present in prostate cancer cells, PSMA is also expressed by a variety of non-prostate cancers, and recent studies have reported on the high uptake of the PSMA ligands 68Ga-PSMA and 18F-DCFPyL in cerebral gliomas.

In response to these findings, this study investigated the regional binding of the well-established PSMA ligands 68Ga-PSMA and 18F-DCFPyL in three different rat glioma models - including the human U87 glioma cell line. Special attention was given to the evaluation of the role of microglia and astroglia, the role of BBB permeability, which was modulated by treatment with dexamethasone (Dex), and the specificity of tracer binding, which was assessed by competition experiments with the PSMA-receptor inhibitor PMPA.

It was found that high uptake of 68Ga-PSMA and 18F-DCFPyL in the peritumoral area of all glioma models could possibly be caused by activated astrocytes. This finding may represent a limitation for the clinical application of PSMA ligands in cerebral gliomas but offers an interesting new insight into the cellular targets that might be involved in the accumulation of PSMA ligands in cerebral gliomas.

Original publication:

High uptake of 68Ga-PSMA-HBED-CC and 18F-DCFPyL in the peritumoral area of rat gliomas due to activated astrocytes


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