Comparative Study of [18F]DPA714 and [18F]FDG PET Tracers in an Experimental Model of Pulmonary Tuberculosis

M. A. Stammes; M. P.M. Vierboom; C. C. Sombroek; J. Bakker; L. Meijer; R. A.W. Vervenne; S. O. Hofman; E. Nutma; I. Kondova; A. D. Windhorst; J. A.M. Langermans; F. A.W. Verreck

doi:10.1007/s11307-025-02057-6

Comparative Study of [¹⁸F]DPA714 and [¹⁸F]FDG PET Tracers in an Experimental Model of Pulmonary Tuberculosis

M. A. Stammes^*
, M. P.M. Vierboom
, C. C. Sombroek
, J. Bakker
, L. Meijer
, R. A.W. Vervenne
, S. O. Hofman
, E. Nutma
, I. Kondova
, A. D. Windhorst
, J. A.M. Langermans
, F. A.W. Verreck

^*Corresponding author for this work

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

Abstract

Purpose: Tuberculosis (TB) continues to afflict global health. Therefore, a deeper understanding of the host response mechanisms that underly pathogenesis versus disease control upon infection with Mycobacterium tuberculosis (Mtb) is required to leverage the development of improved therapeutic or prophylactic TB treatment regimens. In the present work positron emission tomography (PET) using [¹⁸F]DPA714 is piloted as a tracer of the mitochondrial translocator protein TSPO that mainly targets macrophages. Procedures: We compared two tracers: [¹⁸F]DPA714 to the widely applied marker [¹⁸F]FDG to visualize the development of experimental pulmonary TB in three rhesus monkeys (Macaca mulatta), that were infected with Mtb by repeated low dose exposure. Next to baseline recordings prior to infectious challenge, two PETs at a two-weeks interval were acquired early after the manifestation of TB infection for each of the respective tracers. Results & Conclusions: Here, we demonstrate that both PET tracers detected Mtb infection. The inflammatory response tracked by [¹⁸F]FDG progressively increased in line with the developing TB pathology, while [¹⁸F]DPA714 showed a transient signal in lungs and lung-draining hilar lymph nodes. This study underpins the potential value of different tracers to investigate cellular and molecular host response cascades in experimental medicine settings, in this case, into a (transient) local involvement of myeloid immune cell activation versus inflammation-associated glucose consumption in pulmonary TB.

Original language	English
Pages (from-to)	943–953
Journal	Molecular Imaging and Biology
Volume	27
Early online date	21 Oct 2025
DOIs	https://doi.org/10.1007/s11307-025-02057-6
Publication status	Published - 2025

Bibliographical note

Publisher Copyright:
© The Author(s) 2025.

Funding

We would like to thank the Animal Science Department, especially the animal caretakers for taking admirable care of the animals. We also thank the radiation protection team for the assistance with all the procedures regarding radioactivity. The following reagent was obtained through the NIH Biodefense and Emerging Infections (BEI) Research Resources Repository, NIAID, NIH: Mycobacterium tuberculosis, Strain Erdman K01 (TMC 107), NR-15404.

Funders	Funder number
TBVAC.Horizon	TMC 107, NR-15404
NIH Biodefense and Emerging Infections (BEI) Research Resources Repository, NIAID

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Lungs
Macaques
Non-human primates
PET-CT
TB
TSPO

Access to Document

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Cite this

Stammes, M. A., Vierboom, M. P. M., Sombroek, C. C., Bakker, J., Meijer, L., Vervenne, R. A. W., Hofman, S. O., Nutma, E., Kondova, I., Windhorst, A. D., Langermans, J. A. M., & Verreck, F. A. W. (2025). Comparative Study of [¹⁸F]DPA714 and [¹⁸F]FDG PET Tracers in an Experimental Model of Pulmonary Tuberculosis. Molecular Imaging and Biology, 27, 943–953. https://doi.org/10.1007/s11307-025-02057-6

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abstract = "Purpose: Tuberculosis (TB) continues to afflict global health. Therefore, a deeper understanding of the host response mechanisms that underly pathogenesis versus disease control upon infection with Mycobacterium tuberculosis (Mtb) is required to leverage the development of improved therapeutic or prophylactic TB treatment regimens. In the present work positron emission tomography (PET) using [18F]DPA714 is piloted as a tracer of the mitochondrial translocator protein TSPO that mainly targets macrophages. Procedures: We compared two tracers: [18F]DPA714 to the widely applied marker [18F]FDG to visualize the development of experimental pulmonary TB in three rhesus monkeys (Macaca mulatta), that were infected with Mtb by repeated low dose exposure. Next to baseline recordings prior to infectious challenge, two PETs at a two-weeks interval were acquired early after the manifestation of TB infection for each of the respective tracers. Results \& Conclusions: Here, we demonstrate that both PET tracers detected Mtb infection. The inflammatory response tracked by [18F]FDG progressively increased in line with the developing TB pathology, while [18F]DPA714 showed a transient signal in lungs and lung-draining hilar lymph nodes. This study underpins the potential value of different tracers to investigate cellular and molecular host response cascades in experimental medicine settings, in this case, into a (transient) local involvement of myeloid immune cell activation versus inflammation-associated glucose consumption in pulmonary TB.",

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year = "2025",

doi = "10.1007/s11307-025-02057-6",

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volume = "27",

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Stammes, MA, Vierboom, MPM, Sombroek, CC, Bakker, J, Meijer, L, Vervenne, RAW, Hofman, SO, Nutma, E, Kondova, I, Windhorst, AD, Langermans, JAM & Verreck, FAW 2025, 'Comparative Study of [¹⁸F]DPA714 and [¹⁸F]FDG PET Tracers in an Experimental Model of Pulmonary Tuberculosis', Molecular Imaging and Biology, vol. 27, pp. 943–953. https://doi.org/10.1007/s11307-025-02057-6

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T1 - Comparative Study of [18F]DPA714 and [18F]FDG PET Tracers in an Experimental Model of Pulmonary Tuberculosis

AU - Stammes, M. A.

AU - Vierboom, M. P.M.

AU - Sombroek, C. C.

AU - Bakker, J.

AU - Meijer, L.

AU - Vervenne, R. A.W.

AU - Hofman, S. O.

AU - Nutma, E.

AU - Kondova, I.

AU - Windhorst, A. D.

AU - Langermans, J. A.M.

AU - Verreck, F. A.W.

PY - 2025

Y1 - 2025

N2 - Purpose: Tuberculosis (TB) continues to afflict global health. Therefore, a deeper understanding of the host response mechanisms that underly pathogenesis versus disease control upon infection with Mycobacterium tuberculosis (Mtb) is required to leverage the development of improved therapeutic or prophylactic TB treatment regimens. In the present work positron emission tomography (PET) using [18F]DPA714 is piloted as a tracer of the mitochondrial translocator protein TSPO that mainly targets macrophages. Procedures: We compared two tracers: [18F]DPA714 to the widely applied marker [18F]FDG to visualize the development of experimental pulmonary TB in three rhesus monkeys (Macaca mulatta), that were infected with Mtb by repeated low dose exposure. Next to baseline recordings prior to infectious challenge, two PETs at a two-weeks interval were acquired early after the manifestation of TB infection for each of the respective tracers. Results & Conclusions: Here, we demonstrate that both PET tracers detected Mtb infection. The inflammatory response tracked by [18F]FDG progressively increased in line with the developing TB pathology, while [18F]DPA714 showed a transient signal in lungs and lung-draining hilar lymph nodes. This study underpins the potential value of different tracers to investigate cellular and molecular host response cascades in experimental medicine settings, in this case, into a (transient) local involvement of myeloid immune cell activation versus inflammation-associated glucose consumption in pulmonary TB.

AB - Purpose: Tuberculosis (TB) continues to afflict global health. Therefore, a deeper understanding of the host response mechanisms that underly pathogenesis versus disease control upon infection with Mycobacterium tuberculosis (Mtb) is required to leverage the development of improved therapeutic or prophylactic TB treatment regimens. In the present work positron emission tomography (PET) using [18F]DPA714 is piloted as a tracer of the mitochondrial translocator protein TSPO that mainly targets macrophages. Procedures: We compared two tracers: [18F]DPA714 to the widely applied marker [18F]FDG to visualize the development of experimental pulmonary TB in three rhesus monkeys (Macaca mulatta), that were infected with Mtb by repeated low dose exposure. Next to baseline recordings prior to infectious challenge, two PETs at a two-weeks interval were acquired early after the manifestation of TB infection for each of the respective tracers. Results & Conclusions: Here, we demonstrate that both PET tracers detected Mtb infection. The inflammatory response tracked by [18F]FDG progressively increased in line with the developing TB pathology, while [18F]DPA714 showed a transient signal in lungs and lung-draining hilar lymph nodes. This study underpins the potential value of different tracers to investigate cellular and molecular host response cascades in experimental medicine settings, in this case, into a (transient) local involvement of myeloid immune cell activation versus inflammation-associated glucose consumption in pulmonary TB.

KW - Lungs

KW - Macaques

KW - Non-human primates

KW - PET-CT

KW - TB

KW - TSPO

UR - https://www.scopus.com/pages/publications/105019348164

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DO - 10.1007/s11307-025-02057-6

M3 - Article

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