Table 1.

Key considerations for the development and clinical translation of bacteria-specific imaging agents.

Challenges	Solutions
Discovery
Bacterial target selection	Target conserved pathways
	Use clinical strains, drug-resistant strains, and bacteria in different metabolic states
Dosage selection	Evaluate the agent using physiologically relevant assays
	Use nano- to picomolar doses in vitro
Bacterial specificity	Use eukaryotic cells and heat-inactivated bacteria as specificity controls
	Select agents showing >100× favorable accumulation in bacteria
Preclinical animal studies
Model selection	Use multiple clinically relevant animal models
	Quantify bacterial burden at infection site at the time of imaging
Control selection	Use sterile inflammation controls within the same animal model
Agent pharmacokinetics	Monitor clearance, half-life, and tissue penetration of agents
	Consider protein binding characteristics and host metabolism
	Use kinetic modeling to evaluate blood pool effects due to leaky vasculature
Clinical studies
Patient selection	Prioritize diseases with clear clinical needs and appropriate bacterial burden
	Enroll patients with confirmed diagnosis of infection using current gold standard
Empiric antibiotic use with variable residual bacterial burden	Select patients who have received limited antibiotic treatment
Specificity determination	Include patients with inflammatory or oncologic conditions as noninfectious disease controls