Novel PET tracers for infection: Host-response, pathogen-specific, and targeted ligands

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Positron emission tomography (PET) has become an essential tool for assessing infectious and inflammatory diseases through radiolabelled tracers that enable non-invasive visualization of biological processes in vivo. The conventional tracer 18 F-fluorodeoxyglucose (¹⁸F-FDG) remains widely used due to its ability to detect increased glucose metabolism associated with inflammatory activity. However, its limited specificity restricts its capacity to distinguish infectious processes from sterile inflammation, malignancy, or immune-mediated conditions. This limitation has driven the development of next-generation PET tracers targeting host immune responses and pathogen-specific molecular pathways. Emerging host-response tracers target immune cell activation markers, inflammatory cytokines, adhesion molecules, and metabolic reprogramming of inflammatory cells. In parallel, pathogen-specific approaches aim to selectively image microbial metabolic pathways, cell wall synthesis, and transport systems such as siderophore-mediated iron uptake. Species and class selective tracers, including 18 F-fluorosorbitol for Enterobacteriaceae, demonstrate promising specificity in preclinical studies. Radiolabelled antibiotics such as 11 C-trimethoprim and antimicrobial peptides including ubiquicidin further exemplify targeted imaging strategies, although resistance mechanisms and pharmacokinetic limitations remain a challenge. Direct fungal and viral imaging present additional complexity due to low target-to-background ratios prompting investigation of radiolabelled siderophores, antibodies, viral antigens, and host-response pathways. Advances in radiochemistry and high-throughput screening are accelerating tracer development. This review highlights recent advances in host-response and pathogen-specific PET tracers, focusing on their mechanistic targets, translational potential, and diagnostic value in infectious and inflammatory diseases. Collectively, these innovations signify a shift toward target specific PET imaging to improve diagnostic precision, therapeutic monitoring, and personalized management of infectious diseases. Created in BioRender. Nemakhavhani, L. (2026), https://BioRender.com/ex6gtr2

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