Longitudinal [18F]GE-180 PET Imaging Facilitates In Vivo Monitoring of TSPO Expression in the GL261 Glioblastoma Mouse Model

Holzgreve, Adrien; Pötter, Dennis; Brendel, Matthias; Orth, Michael; Weidner, Lorraine; Gold, Lukas; Kirchner, Maximilian A.; Bartos, Laura M.; Unterrainer, Lena M.; Unterrainer, Marcus; Steiger, Katja; von Baumgarten, Louisa; Niyazi, Maximilian; Belka, Claus; Bartenstein, Peter; Riemenschneider, Markus J.; Lauber, Kirsten; Albert, Nathalie L.

doi:10.3390/biomedicines10040738

Open AccessArticle

Longitudinal [¹⁸F]GE-180 PET Imaging Facilitates In Vivo Monitoring of TSPO Expression in the GL261 Glioblastoma Mouse Model

by

Adrien Holzgreve

^1,†

,

Dennis Pötter

^1,†,

Matthias Brendel

¹,

Michael Orth

²

,

Lorraine Weidner

³,

Lukas Gold

¹,

Maximilian A. Kirchner

¹,

Laura M. Bartos

¹,

Lena M. Unterrainer

¹,

Marcus Unterrainer

^4,5

,

Katja Steiger

^5,6

,

Louisa von Baumgarten

^5,7,

Maximilian Niyazi

^2,5,

Claus Belka

^2,5,

Peter Bartenstein

^1,5,

Markus J. Riemenschneider

³,

Kirsten Lauber

^2,5 and

Nathalie L. Albert

^1,5,*

¹

Department of Nuclear Medicine, University Hospital, Ludwig Maximilian University of Munich (LMU Munich), 81377 Munich, Germany

²

Department of Radiation Oncology, University Hospital, Ludwig Maximilian University of Munich (LMU Munich), 81377 Munich, Germany

³

Department of Neuropathology, Regensburg University Hospital, 93053 Regensburg, Germany

⁴

Department of Radiology, University Hospital, Ludwig Maximilian University of Munich (LMU Munich), 81377 Munich, Germany

⁵

German Cancer Consortium (DKTK), Partner Site Munich, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany

⁶

Institute of Pathology, TUM School of Medicine, Technical University of Munich, 81675 Munich, Germany

⁷

Department of Neurosurgery, University Hospital, Ludwig Maximilian University of Munich (LMU Munich), 81377 Munich, Germany

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Biomedicines 2022, 10(4), 738; https://doi.org/10.3390/biomedicines10040738

Submission received: 19 February 2022 / Revised: 17 March 2022 / Accepted: 21 March 2022 / Published: 22 March 2022

(This article belongs to the Special Issue New Generation Imaging in Oncology 2.0)

Download

Browse Figures

Versions Notes

Abstract

The 18 kDa translocator protein (TSPO) is increasingly recognized as an interesting target for the imaging of glioblastoma (GBM). Here, we investigated TSPO PET imaging and autoradiography in the frequently used GL261 glioblastoma mouse model and aimed to generate insights into the temporal evolution of TSPO radioligand uptake in glioblastoma in a preclinical setting. We performed a longitudinal [¹⁸F]GE-180 PET imaging study from day 4 to 14 post inoculation in the orthotopic syngeneic GL261 GBM mouse model (n = 21 GBM mice, n = 3 sham mice). Contrast-enhanced computed tomography (CT) was performed at the day of the final PET scan (±1 day). [¹⁸F]GE-180 autoradiography was performed on day 7, 11 and 14 (ex vivo: n = 13 GBM mice, n = 1 sham mouse; in vitro: n = 21 GBM mice; n = 2 sham mice). Brain sections were also used for hematoxylin and eosin (H&E) staining and TSPO immunohistochemistry. [¹⁸F]GE-180 uptake in PET was elevated at the site of inoculation in GBM mice as compared to sham mice at day 11 and later (at day 14, TBR_max +27% compared to sham mice, p = 0.001). In GBM mice, [¹⁸F]GE-180 uptake continuously increased over time, e.g., at day 11, mean TBR_max +16% compared to day 4, p = 0.011. [¹⁸F]GE-180 uptake as depicted by PET was in all mice co-localized with contrast-enhancement in CT and tissue-based findings. [¹⁸F]GE-180 ex vivo and in vitro autoradiography showed highly congruent tracer distribution (r = 0.99, n = 13, p < 0.001). In conclusion, [¹⁸F]GE-180 PET imaging facilitates non-invasive in vivo monitoring of TSPO expression in the GL261 GBM mouse model. [¹⁸F]GE-180 in vitro autoradiography is a convenient surrogate for ex vivo autoradiography, allowing for straightforward identification of suitable models and scan time-points on previously generated tissue sections.

Keywords: [¹⁸F]GE-180 PET; 18 kDa translocator protein (TSPO); GL261; glioblastoma; ex vivo and in vitro autoradiography

Share and Cite

MDPI and ACS Style

Holzgreve, A.; Pötter, D.; Brendel, M.; Orth, M.; Weidner, L.; Gold, L.; Kirchner, M.A.; Bartos, L.M.; Unterrainer, L.M.; Unterrainer, M.; et al. Longitudinal [¹⁸F]GE-180 PET Imaging Facilitates In Vivo Monitoring of TSPO Expression in the GL261 Glioblastoma Mouse Model. Biomedicines 2022, 10, 738. https://doi.org/10.3390/biomedicines10040738

AMA Style

Holzgreve A, Pötter D, Brendel M, Orth M, Weidner L, Gold L, Kirchner MA, Bartos LM, Unterrainer LM, Unterrainer M, et al. Longitudinal [¹⁸F]GE-180 PET Imaging Facilitates In Vivo Monitoring of TSPO Expression in the GL261 Glioblastoma Mouse Model. Biomedicines. 2022; 10(4):738. https://doi.org/10.3390/biomedicines10040738

Chicago/Turabian Style

Holzgreve, Adrien, Dennis Pötter, Matthias Brendel, Michael Orth, Lorraine Weidner, Lukas Gold, Maximilian A. Kirchner, Laura M. Bartos, Lena M. Unterrainer, Marcus Unterrainer, and et al. 2022. "Longitudinal [¹⁸F]GE-180 PET Imaging Facilitates In Vivo Monitoring of TSPO Expression in the GL261 Glioblastoma Mouse Model" Biomedicines 10, no. 4: 738. https://doi.org/10.3390/biomedicines10040738

APA Style

Holzgreve, A., Pötter, D., Brendel, M., Orth, M., Weidner, L., Gold, L., Kirchner, M. A., Bartos, L. M., Unterrainer, L. M., Unterrainer, M., Steiger, K., von Baumgarten, L., Niyazi, M., Belka, C., Bartenstein, P., Riemenschneider, M. J., Lauber, K., & Albert, N. L. (2022). Longitudinal [¹⁸F]GE-180 PET Imaging Facilitates In Vivo Monitoring of TSPO Expression in the GL261 Glioblastoma Mouse Model. Biomedicines, 10(4), 738. https://doi.org/10.3390/biomedicines10040738

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

Longitudinal [¹⁸F]GE-180 PET Imaging Facilitates In Vivo Monitoring of TSPO Expression in the GL261 Glioblastoma Mouse Model

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI