Translocator protein (TSPO) positron emission tomography imaging and expression in patients with brain metastases

Paolo Zanotti-Fregonara; Monika Vishnoi; Quentin Finn; John D. Patterson; Aboud Tahanis; David R. Beers; Oluwaseun B. Ogunbona; Belen Pascual; Joseph C. Masdeu; Steve H. Fung; Nafiseh Ghazanfari; Kanayo Ikeneme; Suzanne Powell; Zheng Yin; Robert C. Rostomily

doi:10.1007/s00259-025-07477-8

Translocator protein (TSPO) positron emission tomography imaging and expression in patients with brain metastases

Paolo Zanotti-Fregonara, Monika Vishnoi, Quentin Finn, John D. Patterson, Aboud Tahanis, David R. Beers, Oluwaseun B. Ogunbona, Belen Pascual, Joseph C. Masdeu, Steve H. Fung, Nafiseh Ghazanfari, Kanayo Ikeneme, Suzanne Powell, Zheng Yin, Robert C. Rostomily

Research output: Contribution to journal › Article › peer-review

Abstract

Purpose: 18 kDa translocator protein (TSPO) is a biomarker for inflammatory conditions. However, full kinetic positron emission tomography (PET) modeling has rarely been used to quantify brain tumors, and it has never been used in brain metastases (BMs). This proof-of-principle study quantified TSPO expression using full kinetic modeling in patients with BMs from various types of peripheral primary tumors. Methods: Nine adult patients with BMs and 12 healthy volunteers (HVs) took part in the study. The total distribution volume (V_T) of ¹¹C-ER176 was calculated with a two-tissue compartment model (2TCM) and metabolite-corrected arterial input function in the BMs and in the rest of the brain. Immunohistochemistry (IHC) and single-cell RNAseq database were used to quantify TSPO expression in vitro. The V_T values of the hemisphere contralateral to the BMs were compared to the cortical values of HVs. Results: ¹¹C-ER176 uptake was increased in BMs compared with the rest of the brain of each participant. The BM time-activity curves were well-fitted by the 2TCM, and the resulting V_T (range 3.2–13 mL/cm³) was identified with precision (standard error generally < 5%). The rate constant mostly affected by the integrity of the blood–brain barrier (BBB) (K₁) was similar between the BMs and the contralateral hemisphere. TSPO expression was detected by IHC in tumor regions and variably in microglia/macrophages, a finding largely corroborated by single-cell RNAseq database. The average V_T of the rest of the brain in BM patients was significantly lower than in HVs, which may have been due to immunosuppressive therapy. Conclusion: In this pilot study, full kinetic modeling quantified TSPO expression in BMs with good fit and precision. The kinetic modeling outcome parameters and the TSPO expression levels in vitro suggest that ¹¹C-ER176 binding was largely specific and not significantly affected by disruption of the BBB.

Original language	English (US)
Pages (from-to)	505-517
Number of pages	13
Journal	European Journal of Nuclear Medicine and Molecular Imaging
Volume	53
Issue number	1
DOIs	https://doi.org/10.1007/s00259-025-07477-8
State	Published - Dec 2025

Keywords

Brain metastasis
Immunohistochemistry
PET imaging
Sc-RNA seq
TSPO

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging

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10.1007/s00259-025-07477-8

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Zanotti-Fregonara, P., Vishnoi, M., Finn, Q., Patterson, J. D., Tahanis, A., Beers, D. R., Ogunbona, O. B., Pascual, B., Masdeu, J. C., Fung, S. H., Ghazanfari, N., Ikeneme, K., Powell, S., Yin, Z., & Rostomily, R. C. (2025). Translocator protein (TSPO) positron emission tomography imaging and expression in patients with brain metastases. European Journal of Nuclear Medicine and Molecular Imaging, 53(1), 505-517. https://doi.org/10.1007/s00259-025-07477-8

Zanotti-Fregonara, P, Vishnoi, M, Finn, Q, Patterson, JD, Tahanis, A, Beers, DR, Ogunbona, OB, Pascual, B , Masdeu, JC , Fung, SH, Ghazanfari, N, Ikeneme, K, Powell, S , Yin, Z & Rostomily, RC 2025, 'Translocator protein (TSPO) positron emission tomography imaging and expression in patients with brain metastases', European Journal of Nuclear Medicine and Molecular Imaging, vol. 53, no. 1, pp. 505-517. https://doi.org/10.1007/s00259-025-07477-8

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title = "Translocator protein (TSPO) positron emission tomography imaging and expression in patients with brain metastases",

abstract = "Purpose: 18 kDa translocator protein (TSPO) is a biomarker for inflammatory conditions. However, full kinetic positron emission tomography (PET) modeling has rarely been used to quantify brain tumors, and it has never been used in brain metastases (BMs). This proof-of-principle study quantified TSPO expression using full kinetic modeling in patients with BMs from various types of peripheral primary tumors. Methods: Nine adult patients with BMs and 12 healthy volunteers (HVs) took part in the study. The total distribution volume (VT) of 11C-ER176 was calculated with a two-tissue compartment model (2TCM) and metabolite-corrected arterial input function in the BMs and in the rest of the brain. Immunohistochemistry (IHC) and single-cell RNAseq database were used to quantify TSPO expression in vitro. The VT values of the hemisphere contralateral to the BMs were compared to the cortical values of HVs. Results: 11C-ER176 uptake was increased in BMs compared with the rest of the brain of each participant. The BM time-activity curves were well-fitted by the 2TCM, and the resulting VT (range 3.2–13 mL/cm3) was identified with precision (standard error generally < 5\%). The rate constant mostly affected by the integrity of the blood–brain barrier (BBB) (K1) was similar between the BMs and the contralateral hemisphere. TSPO expression was detected by IHC in tumor regions and variably in microglia/macrophages, a finding largely corroborated by single-cell RNAseq database. The average VT of the rest of the brain in BM patients was significantly lower than in HVs, which may have been due to immunosuppressive therapy. Conclusion: In this pilot study, full kinetic modeling quantified TSPO expression in BMs with good fit and precision. The kinetic modeling outcome parameters and the TSPO expression levels in vitro suggest that 11C-ER176 binding was largely specific and not significantly affected by disruption of the BBB.",

keywords = "Brain metastasis, Immunohistochemistry, PET imaging, Sc-RNA seq, TSPO",

author = "Paolo Zanotti-Fregonara and Monika Vishnoi and Quentin Finn and Patterson, \{John D.\} and Aboud Tahanis and Beers, \{David R.\} and Ogunbona, \{Oluwaseun B.\} and Belen Pascual and Masdeu, \{Joseph C.\} and Fung, \{Steve H.\} and Nafiseh Ghazanfari and Kanayo Ikeneme and Suzanne Powell and Zheng Yin and Rostomily, \{Robert C.\}",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025.",

year = "2025",

month = dec,

doi = "10.1007/s00259-025-07477-8",

language = "English (US)",

volume = "53",

pages = "505--517",

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T1 - Translocator protein (TSPO) positron emission tomography imaging and expression in patients with brain metastases

AU - Zanotti-Fregonara, Paolo

AU - Vishnoi, Monika

AU - Finn, Quentin

AU - Patterson, John D.

AU - Tahanis, Aboud

AU - Beers, David R.

AU - Ogunbona, Oluwaseun B.

AU - Pascual, Belen

AU - Masdeu, Joseph C.

AU - Fung, Steve H.

AU - Ghazanfari, Nafiseh

AU - Ikeneme, Kanayo

AU - Powell, Suzanne

AU - Yin, Zheng

AU - Rostomily, Robert C.

N1 - Publisher Copyright: © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025.

PY - 2025/12

Y1 - 2025/12

N2 - Purpose: 18 kDa translocator protein (TSPO) is a biomarker for inflammatory conditions. However, full kinetic positron emission tomography (PET) modeling has rarely been used to quantify brain tumors, and it has never been used in brain metastases (BMs). This proof-of-principle study quantified TSPO expression using full kinetic modeling in patients with BMs from various types of peripheral primary tumors. Methods: Nine adult patients with BMs and 12 healthy volunteers (HVs) took part in the study. The total distribution volume (VT) of 11C-ER176 was calculated with a two-tissue compartment model (2TCM) and metabolite-corrected arterial input function in the BMs and in the rest of the brain. Immunohistochemistry (IHC) and single-cell RNAseq database were used to quantify TSPO expression in vitro. The VT values of the hemisphere contralateral to the BMs were compared to the cortical values of HVs. Results: 11C-ER176 uptake was increased in BMs compared with the rest of the brain of each participant. The BM time-activity curves were well-fitted by the 2TCM, and the resulting VT (range 3.2–13 mL/cm3) was identified with precision (standard error generally < 5%). The rate constant mostly affected by the integrity of the blood–brain barrier (BBB) (K1) was similar between the BMs and the contralateral hemisphere. TSPO expression was detected by IHC in tumor regions and variably in microglia/macrophages, a finding largely corroborated by single-cell RNAseq database. The average VT of the rest of the brain in BM patients was significantly lower than in HVs, which may have been due to immunosuppressive therapy. Conclusion: In this pilot study, full kinetic modeling quantified TSPO expression in BMs with good fit and precision. The kinetic modeling outcome parameters and the TSPO expression levels in vitro suggest that 11C-ER176 binding was largely specific and not significantly affected by disruption of the BBB.

AB - Purpose: 18 kDa translocator protein (TSPO) is a biomarker for inflammatory conditions. However, full kinetic positron emission tomography (PET) modeling has rarely been used to quantify brain tumors, and it has never been used in brain metastases (BMs). This proof-of-principle study quantified TSPO expression using full kinetic modeling in patients with BMs from various types of peripheral primary tumors. Methods: Nine adult patients with BMs and 12 healthy volunteers (HVs) took part in the study. The total distribution volume (VT) of 11C-ER176 was calculated with a two-tissue compartment model (2TCM) and metabolite-corrected arterial input function in the BMs and in the rest of the brain. Immunohistochemistry (IHC) and single-cell RNAseq database were used to quantify TSPO expression in vitro. The VT values of the hemisphere contralateral to the BMs were compared to the cortical values of HVs. Results: 11C-ER176 uptake was increased in BMs compared with the rest of the brain of each participant. The BM time-activity curves were well-fitted by the 2TCM, and the resulting VT (range 3.2–13 mL/cm3) was identified with precision (standard error generally < 5%). The rate constant mostly affected by the integrity of the blood–brain barrier (BBB) (K1) was similar between the BMs and the contralateral hemisphere. TSPO expression was detected by IHC in tumor regions and variably in microglia/macrophages, a finding largely corroborated by single-cell RNAseq database. The average VT of the rest of the brain in BM patients was significantly lower than in HVs, which may have been due to immunosuppressive therapy. Conclusion: In this pilot study, full kinetic modeling quantified TSPO expression in BMs with good fit and precision. The kinetic modeling outcome parameters and the TSPO expression levels in vitro suggest that 11C-ER176 binding was largely specific and not significantly affected by disruption of the BBB.

KW - Brain metastasis

KW - Immunohistochemistry

KW - PET imaging

KW - Sc-RNA seq

KW - TSPO

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Translocator protein (TSPO) positron emission tomography imaging and expression in patients with brain metastases

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