The Impact of PET Imaging on Translational Medicine: Insights from Large-Animal Disease Models

Abstract

Large-animal models are playing a pivotal role in bridging the translational research gap. Positron emission tomography (PET) imaging is preferred in disease research involving large-animal models. Its ability to non-invasively monitor metabolic activity, receptor-ligand interactions, and pharmacokinetics in real time makes PET imaging an essential tool for evaluating therapeutic efficacy and advancing the development of targeted treatments. This review focuses on recent advancements in dedicated large-animal PET scanners, the utilization of large-animal models for simulating human diseases, and their applications in PET studies. It specifically highlights the critical role of PET imaging in facilitating the development of more effective and safer treatments for infections, chronic heart disease, diabetes, cancer, central nervous system disorders, and addiction, emphasizing its importance in the translational research landscape.

Keywords: biomarker discovery; cardiovascular imaging; infection; large animals; metabolic disease; neurology; positron emission tomography.

Figure 1

Comparison between different systems. (A) Differences in volumetric resolution of different systems; (B) differences in sensitivity of different systems. Volumetric resolution refers to the ability of an imaging system to distinguish between two or more objects in three-dimensional space. It is a measure of how well the system can resolve details in all three dimensions: radial (r), tangential (t), and axial (z). Volumetric Resolution (mm³) = (Radial × Tangential × Axial).

Figure 2

Maximum-intensity-projection images from [¹⁸F]FDG rhesus monkey study: 1 s frame at 5 s after injection (A), 0–30 s after injection (B), 55–60 min after injection (C), and 18 h after injection (40 min scan) (D). This research was originally published in JNM. Eric Berg et al. Development and Evaluation of mini-EXPLORER: A Long Axial Field-of-View PET Scanner for Non-human Primate Imaging. J Nucl Med. June 2018, 59(6), 993–998. © SNMMI.

Figure 3

Longitudinal development of both lung lesions and metabolic activity in tracheobronchial lymph nodes of a cynomolgus macaque over time after a SARS-CoV-2 infection. Representative coronal slices with a thickness of 3 mm of the cynomolgus macaque were used for visualization. On days 0 and 4, only CT images were obtained; afterwards, until day 35, CT was combined with PET (LFER 150). The location of the lesions, marked with arrows, differed almost per time point but are most prominently localized in the left lung on day 35. This research was originally published in Viruses. Böszörményi, K.P. et al., The Post-Acute Phase of SARS-CoV-2 Infection in Two Macaque Species Is Associated with Signs of Ongoing Virus Replication and Pathology in Pulmonary and Extrapulmonary Tissues. Viruses, 2021. 13(8).

Figure 4

PET examination on HD sheep. (A) Average glucose uptake images showing the coronal, sagittal, and axial views in each group (n = 3/group). The averaged PET images are overlaid onto the MRI template for anatomical reference. (B) Imaging dopamine metabolism using [¹⁸F]FDOPA. Tracer uptake assessment and averaged [¹⁸F]FDOPA parametric maps for control, 5.5 Y, and 11 Y HD sheep (n = 3/group) are overlaid onto the T1w MRI template for anatomical reference. Reprinted (adapted) with permission from Williams, G. K., Akkermans, J., Lawson, M., Syta, P., Staelens, S., Adhikari, M. H., Morton, A. J., Nitzsche, B., Boltze, J., Christou, C., Bertoglio, D., & Ahamed, M. (2024). Imaging Glucose Metabolism and Dopaminergic Dysfunction in Sheep (Ovis aries) Brain Using Positron Emission Tomography Imaging Reveals Abnormalities in OVT73 Huntington’s Disease Sheep. ACS chemical neuroscience, 15(21), 4082–4091. https://doi.org/10.1021/acschemneuro.4c00561. Copyright 2025 American Chemical Society.