PET imaging of mycobacterial infection: transforming the pipeline for tuberculosis drug development

Abstract

Improved PET/CT radiopharmaceuticals can better visualize and monitor tuberculosis and enable real-time pharmacological drug profiling in vivo. PET/CT imaging can therefore be used to study in animal models the changes in tissue pathology in tuberculosis infection, such as mycobacterial latency, tuberculoma formation, lung cavitation or calcification, and extrapulmonary disease. This Perspective aims to critically evaluate the current and future contribution and role of PET imaging in anti-tuberculosis drug development.

Fig. 1. Interplay of complications during anti-mycobacterial therapy^,.

Figure created using a licensed version of Biorender.com.

Fig. 2. Available antibiotics for targeted MTb treatment and their mechanism of action.

The figure includes standard therapy agents (red font color) and investigational drugs (blue font color) in advanced trials^,. Figure created using a licensed version of Biorender.com.

Fig. 3. Implementation of PET/CT in the MTb drug development pipeline.

* a radiolabeled (e.g., Fluorine-18 or Carbon-11) biosimilar version of the anti-TB drug will enable PET/CT imaging (non-invasive, longitudinal, quantitative investigations) for in vivo characterization. Figure created using a licensed version of Biorender.com.

Fig. 4. Comparing relevant animal models for evaluation of novel anti-MTb therapies.

*Human pathology is not replicated accurately, with the exception of specialized animal models like the C3HeB/FeJ ‘Kramnik’ mouse model. Figure created using a licensed version of Biorender.com.

Fig. 5. An example of the pharmacokinetic evaluation of Pretomanid using the biosimilar radioactive derivative [¹⁸F]Pretomanid and PET/CT imaging^,.

The structure of the unradioactive (A) and fluorine-18 labelled (B) compound is provided. Biological evaluation in a mouse model (C), rabbit model (D) and human subjects (E) was performed.

Fig. 6. PET imaging further characterizing cerebral Pretomanid-based effects, using selected established radiopharmaceuticals.

The figure demonstrates the distribution of A [¹⁸F]FDG and B [¹²⁴I]iodo-DPA-713. Figure content was adopted from a previous publication. Parts of the figure were created using a licensed version of Biorender.com.