High uptake of 68Ga-PSMA and 18F-DCFPyL in the peritumoral area of rat gliomas due to activated astrocytes
Abstract Background Recent 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. Methods F98, 9 L, or U87 rat gli...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2020-05-01
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| Series: | EJNMMI Research |
| Online Access: | http://link.springer.com/article/10.1186/s13550-020-00642-0 |
| _version_ | 1819092902670761984 |
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| author | Dennis Oliveira Carina Stegmayr Alexander Heinzel Johannes Ermert Bernd Neumaier N. Jon Shah Felix M. Mottaghy Karl-Josef Langen Antje Willuweit |
| author_facet | Dennis Oliveira Carina Stegmayr Alexander Heinzel Johannes Ermert Bernd Neumaier N. Jon Shah Felix M. Mottaghy Karl-Josef Langen Antje Willuweit |
| author_sort | Dennis Oliveira |
| collection | DOAJ |
| description | Abstract Background Recent 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. Methods F98, 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. Results Autoradiography 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. Conclusions High 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. |
| first_indexed | 2024-12-21T23:03:00Z |
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| id | doaj.art-ae43ee80bc9c463499fe50eb71a840c0 |
| institution | Directory Open Access Journal |
| issn | 2191-219X |
| language | English |
| last_indexed | 2024-12-21T23:03:00Z |
| publishDate | 2020-05-01 |
| publisher | SpringerOpen |
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| series | EJNMMI Research |
| spelling | doaj.art-ae43ee80bc9c463499fe50eb71a840c02022-12-21T18:47:15ZengSpringerOpenEJNMMI Research2191-219X2020-05-0110111110.1186/s13550-020-00642-0High uptake of 68Ga-PSMA and 18F-DCFPyL in the peritumoral area of rat gliomas due to activated astrocytesDennis Oliveira0Carina Stegmayr1Alexander Heinzel2Johannes Ermert3Bernd Neumaier4N. Jon Shah5Felix M. Mottaghy6Karl-Josef Langen7Antje Willuweit8Institute of Neuroscience and Medicine (INM), Forschungszentrum JülichInstitute of Neuroscience and Medicine (INM), Forschungszentrum JülichDepartment of Nuclear Medicine, RWTH Aachen UniversityInstitute of Neuroscience and Medicine (INM), Forschungszentrum JülichInstitute of Neuroscience and Medicine (INM), Forschungszentrum JülichInstitute of Neuroscience and Medicine (INM), Forschungszentrum JülichDepartment of Nuclear Medicine, RWTH Aachen UniversityInstitute of Neuroscience and Medicine (INM), Forschungszentrum JülichInstitute of Neuroscience and Medicine (INM), Forschungszentrum JülichAbstract Background Recent 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. Methods F98, 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. Results Autoradiography 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. Conclusions High 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.http://link.springer.com/article/10.1186/s13550-020-00642-0 |
| spellingShingle | Dennis Oliveira Carina Stegmayr Alexander Heinzel Johannes Ermert Bernd Neumaier N. Jon Shah Felix M. Mottaghy Karl-Josef Langen Antje Willuweit High uptake of 68Ga-PSMA and 18F-DCFPyL in the peritumoral area of rat gliomas due to activated astrocytes EJNMMI Research |
| title | High uptake of 68Ga-PSMA and 18F-DCFPyL in the peritumoral area of rat gliomas due to activated astrocytes |
| title_full | High uptake of 68Ga-PSMA and 18F-DCFPyL in the peritumoral area of rat gliomas due to activated astrocytes |
| title_fullStr | High uptake of 68Ga-PSMA and 18F-DCFPyL in the peritumoral area of rat gliomas due to activated astrocytes |
| title_full_unstemmed | High uptake of 68Ga-PSMA and 18F-DCFPyL in the peritumoral area of rat gliomas due to activated astrocytes |
| title_short | High uptake of 68Ga-PSMA and 18F-DCFPyL in the peritumoral area of rat gliomas due to activated astrocytes |
| title_sort | high uptake of 68ga psma and 18f dcfpyl in the peritumoral area of rat gliomas due to activated astrocytes |
| url | http://link.springer.com/article/10.1186/s13550-020-00642-0 |
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