PSMA PET Imaging in Glioblastoma: A Preclinical Evaluation and Theranostic Outlook

BackgroundProstate specific membrane antigen (PSMA) PET imaging has recently gained attention in glioblastoma (GBM) patients as a potential theranostic target for PSMA radioligand therapy. However, PSMA PET has not yet been established in a murine GBM model. Our goal was to investigate the potential...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Maximilian A. Kirchner, Adrien Holzgreve, Matthias Brendel, Michael Orth, Viktoria C. Ruf, Katja Steiger, Dennis Pötter, Lukas Gold, Marcus Unterrainer, Lena M. Mittlmeier, Enio Barci, Roland E. Kälin, Rainer Glass, Simon Lindner, Lena Kaiser, Jessica Maas, Louisa von Baumgarten, Harun Ilhan, Claus Belka, Johannes Notni, Peter Bartenstein, Kirsten Lauber, Nathalie L. Albert
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Prostate specific membrane antigen (PSMA) 18F-PSMA-1007 PET glioblastoma GL261 preclinical mouse Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/a33fdca79420480f90602dfda9688c64
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a33fdca79420480f90602dfda9688c64
record_format	dspace
spelling	oai:doaj.org-article:a33fdca79420480f90602dfda9688c642021-11-17T05:04:35ZPSMA PET Imaging in Glioblastoma: A Preclinical Evaluation and Theranostic Outlook2234-943X10.3389/fonc.2021.774017https://doaj.org/article/a33fdca79420480f90602dfda9688c642021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.774017/fullhttps://doaj.org/toc/2234-943XBackgroundProstate specific membrane antigen (PSMA) PET imaging has recently gained attention in glioblastoma (GBM) patients as a potential theranostic target for PSMA radioligand therapy. However, PSMA PET has not yet been established in a murine GBM model. Our goal was to investigate the potential of PSMA PET imaging in the syngeneic GL261 GBM model and to give an outlook regarding the potential of PMSA radioligand therapy in this model.MethodsWe performed an 18F-PSMA-1007 PET study in the orthotopic GL261 model (n=14 GBM, n=7 sham-operated mice) with imaging at day 4, 8, 11, 15, 18 and 22 post implantation. Time-activity-curves (TAC) were extracted from dynamic PET scans (0-120 min p. i.) in a subset of mice (n=4 GBM, n=3 sham-operated mice) to identify the optimal time frame for image analysis, and standardized-uptake-values (SUV) as well as tumor-to-background ratios (TBR) using contralateral normal brain as background were calculated in all mice. Additionally, computed tomography (CT), ex vivo and in vitro18F-PSMA-1007 autoradiographies (ARG) were performed.ResultsTAC analysis of GBM mice revealed a plateau of TBR values after 40 min p. i. Therefore, a 30 min time frame between 40-70 min p. i. was chosen for PET quantification. At day 15 and later, GBM mice showed a discernible PSMA PET signal on the inoculation site, with highest TBRmean in GBM mice at day 18 (7.3 ± 1.3 vs. 1.6 ± 0.3 in shams; p=0.024). Ex vivo ARG confirmed high tracer signal in GBM compared to healthy background (TBRmean 26.9 ± 10.5 vs. 1.6 ± 0.7 in shams at day 18/22 post implantation; p=0.002). However, absolute uptake values in the GL261 tumor remained low (e.g., SUVmean 0.21 ± 0.04 g/ml at day 18) resulting in low ratios compared to dose-relevant organs (e.g., mean tumor-to-kidney ratio 1.5E-2 ± 0.5E-2).ConclusionsAlthough 18F-PSMA-1007 PET imaging of GL261 tumor-bearing mice is feasible and resulted in high TBRs, absolute tumoral uptake values remained low and hint to limited applicability of the GL261 model for PSMA-directed therapy studies. Further investigations are warranted to identify suitable models for preclinical evaluation of PSMA-targeted theranostic approaches in GBM.Maximilian A. KirchnerAdrien HolzgreveMatthias BrendelMichael OrthViktoria C. RufKatja SteigerDennis PötterLukas GoldMarcus UnterrainerMarcus UnterrainerLena M. MittlmeierEnio BarciRoland E. KälinRainer GlassRainer GlassSimon LindnerLena KaiserJessica MaasLouisa von BaumgartenHarun IlhanClaus BelkaClaus BelkaJohannes NotniPeter BartensteinPeter BartensteinKirsten LauberKirsten LauberNathalie L. AlbertNathalie L. AlbertFrontiers Media S.A.articleProstate specific membrane antigen (PSMA)18F-PSMA-1007 PETglioblastomaGL261preclinicalmouseNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Prostate specific membrane antigen (PSMA) 18F-PSMA-1007 PET glioblastoma GL261 preclinical mouse Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Prostate specific membrane antigen (PSMA) 18F-PSMA-1007 PET glioblastoma GL261 preclinical mouse Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Maximilian A. Kirchner Adrien Holzgreve Matthias Brendel Michael Orth Viktoria C. Ruf Katja Steiger Dennis Pötter Lukas Gold Marcus Unterrainer Marcus Unterrainer Lena M. Mittlmeier Enio Barci Roland E. Kälin Rainer Glass Rainer Glass Simon Lindner Lena Kaiser Jessica Maas Louisa von Baumgarten Harun Ilhan Claus Belka Claus Belka Johannes Notni Peter Bartenstein Peter Bartenstein Kirsten Lauber Kirsten Lauber Nathalie L. Albert Nathalie L. Albert PSMA PET Imaging in Glioblastoma: A Preclinical Evaluation and Theranostic Outlook
description	BackgroundProstate specific membrane antigen (PSMA) PET imaging has recently gained attention in glioblastoma (GBM) patients as a potential theranostic target for PSMA radioligand therapy. However, PSMA PET has not yet been established in a murine GBM model. Our goal was to investigate the potential of PSMA PET imaging in the syngeneic GL261 GBM model and to give an outlook regarding the potential of PMSA radioligand therapy in this model.MethodsWe performed an 18F-PSMA-1007 PET study in the orthotopic GL261 model (n=14 GBM, n=7 sham-operated mice) with imaging at day 4, 8, 11, 15, 18 and 22 post implantation. Time-activity-curves (TAC) were extracted from dynamic PET scans (0-120 min p. i.) in a subset of mice (n=4 GBM, n=3 sham-operated mice) to identify the optimal time frame for image analysis, and standardized-uptake-values (SUV) as well as tumor-to-background ratios (TBR) using contralateral normal brain as background were calculated in all mice. Additionally, computed tomography (CT), ex vivo and in vitro18F-PSMA-1007 autoradiographies (ARG) were performed.ResultsTAC analysis of GBM mice revealed a plateau of TBR values after 40 min p. i. Therefore, a 30 min time frame between 40-70 min p. i. was chosen for PET quantification. At day 15 and later, GBM mice showed a discernible PSMA PET signal on the inoculation site, with highest TBRmean in GBM mice at day 18 (7.3 ± 1.3 vs. 1.6 ± 0.3 in shams; p=0.024). Ex vivo ARG confirmed high tracer signal in GBM compared to healthy background (TBRmean 26.9 ± 10.5 vs. 1.6 ± 0.7 in shams at day 18/22 post implantation; p=0.002). However, absolute uptake values in the GL261 tumor remained low (e.g., SUVmean 0.21 ± 0.04 g/ml at day 18) resulting in low ratios compared to dose-relevant organs (e.g., mean tumor-to-kidney ratio 1.5E-2 ± 0.5E-2).ConclusionsAlthough 18F-PSMA-1007 PET imaging of GL261 tumor-bearing mice is feasible and resulted in high TBRs, absolute tumoral uptake values remained low and hint to limited applicability of the GL261 model for PSMA-directed therapy studies. Further investigations are warranted to identify suitable models for preclinical evaluation of PSMA-targeted theranostic approaches in GBM.
format	article
author	Maximilian A. Kirchner Adrien Holzgreve Matthias Brendel Michael Orth Viktoria C. Ruf Katja Steiger Dennis Pötter Lukas Gold Marcus Unterrainer Marcus Unterrainer Lena M. Mittlmeier Enio Barci Roland E. Kälin Rainer Glass Rainer Glass Simon Lindner Lena Kaiser Jessica Maas Louisa von Baumgarten Harun Ilhan Claus Belka Claus Belka Johannes Notni Peter Bartenstein Peter Bartenstein Kirsten Lauber Kirsten Lauber Nathalie L. Albert Nathalie L. Albert
author_facet	Maximilian A. Kirchner Adrien Holzgreve Matthias Brendel Michael Orth Viktoria C. Ruf Katja Steiger Dennis Pötter Lukas Gold Marcus Unterrainer Marcus Unterrainer Lena M. Mittlmeier Enio Barci Roland E. Kälin Rainer Glass Rainer Glass Simon Lindner Lena Kaiser Jessica Maas Louisa von Baumgarten Harun Ilhan Claus Belka Claus Belka Johannes Notni Peter Bartenstein Peter Bartenstein Kirsten Lauber Kirsten Lauber Nathalie L. Albert Nathalie L. Albert
author_sort	Maximilian A. Kirchner
title	PSMA PET Imaging in Glioblastoma: A Preclinical Evaluation and Theranostic Outlook
title_short	PSMA PET Imaging in Glioblastoma: A Preclinical Evaluation and Theranostic Outlook
title_full	PSMA PET Imaging in Glioblastoma: A Preclinical Evaluation and Theranostic Outlook
title_fullStr	PSMA PET Imaging in Glioblastoma: A Preclinical Evaluation and Theranostic Outlook
title_full_unstemmed	PSMA PET Imaging in Glioblastoma: A Preclinical Evaluation and Theranostic Outlook
title_sort	psma pet imaging in glioblastoma: a preclinical evaluation and theranostic outlook
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/a33fdca79420480f90602dfda9688c64
work_keys_str_mv	AT maximilianakirchner psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT adrienholzgreve psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT matthiasbrendel psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT michaelorth psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT viktoriacruf psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT katjasteiger psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT dennispotter psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT lukasgold psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT marcusunterrainer psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT marcusunterrainer psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT lenammittlmeier psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT eniobarci psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT rolandekalin psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT rainerglass psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT rainerglass psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT simonlindner psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT lenakaiser psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT jessicamaas psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT louisavonbaumgarten psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT harunilhan psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT clausbelka psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT clausbelka psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT johannesnotni psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT peterbartenstein psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT peterbartenstein psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT kirstenlauber psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT kirstenlauber psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT nathalielalbert psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook AT nathalielalbert psmapetimaginginglioblastomaapreclinicalevaluationandtheranosticoutlook
_version_	1718425944922783744

PSMA PET Imaging in Glioblastoma: A Preclinical Evaluation and Theranostic Outlook

Ejemplares similares