. 2021 Oct 26;22(21):11552. doi: 10.3390/ijms222111552

Table 4.

Emerging Investigational Radiotracers of Infection Imaging.

	Radiotracer	Clinical Trials	Parameter	Mechanism of Localization	Strength/Weakness	References
Radiolabeled Antibiotics	^99mTc-ciprofloxacin	Yes	Inhibition of DNA Synthesis	Bacterial DNA gyrase	High sensitivity (85.4–97.2%), ciprofloxacin already used in DFI treatment	[133,134,135,136]
	^99mTc-ciprofloxacin	Yes	Inhibition of DNA Synthesis	Bacterial DNA gyrase	Low specificity (66.7–81.7%), antibiotic resistant bacteria	[133,134,135,136]
	¹⁸F-fluoropropyl-trimethoprim	No	Inhibition of Folic Acid Synthesis	Inhibition of thymidine biosynthesis	Low background, high uptake in bacteria, detect inflammation from soft tissue infection vs sterile inflammation	[167]
	¹⁸F-fluoropropyl-trimethoprim	No	Inhibition of Folic Acid Synthesis		Antibiotic resistant bacteria	[167]
	^99mTc-sulfonamides (pertechnetate, sulfadiazine)	No	Inhibition of Folic Acid Synthesis		Broad spectrum antibiotics, uptake in bacterial and fungal infections	[155]
	^99mTc-sulfonamides (pertechnetate, sulfadiazine)	No	Inhibition of Folic Acid Synthesis		Antibiotic resistant bacteria	[155]
	^99mTc-vancomycin	No	Inhibition of bacterial cell wall synthesis	Binds to D-ala-D-ala lipid moiety	Specific for gram positive organisms	[137,138,139]
	^99mTc-vancomycin	No	Inhibition of bacterial cell wall synthesis	Binds to D-ala-D-ala lipid moiety	Not specific for gram negative organisms Antibiotic resistant bacteria	[137,138,139]
Radiolabeled Sugars	¹⁸F-FDS	Yes	Bacteria-Specific Glucose Sources for Carbohydrate Metabolism	Bacterial Metabolic Substrate	Antibiotic treatment monitoring, used in humans	[140,141]
	¹⁸F-FDS	Yes		Bacterial Metabolic Substrate	Uptake by Enterobacteriaceae in the human gut	[140,141]
	¹⁸F-FAG	No		Sorbitol analogue utilized only by bacteria	Selective accumulation in E. coli, rapid accumulation, can differentiate infection from sterile inflammation, shows promise for monitoring response to treatment, small molecule	[142]
	¹⁸F-FAG	No		Sorbitol analogue utilized only by bacteria	Not applied clinically	[142]
	¹⁸F-maltohexose	No		Bacterial-specific maltodextrin transporter	Can discriminate between live bacteria, metabolically inactive bacteria, and sterile inflammation	[143]
	¹⁸F-maltohexose	No		Bacterial-specific maltodextrin transporter	Poor signal-to-noise ratios, Not applied clinically	[143]
	6′′-¹⁸F-fluoromaltotriose	No		Bacterial-specific maltodextrin transporter	2nd Gen, improved signal-to-noise ratio, bacterial-selective uptake in vitro and in vivo	[144,145]
	6′′-¹⁸F-fluoromaltotriose	No		Bacterial-specific maltodextrin transporter	Not applied clinically	[144,145]
Amino Acid Uptake	D-[methyl-¹¹C] methionine	No	Bacterial Cell Wall Synthesis	Incorporation into the peptidoglycan	Distinguish sterile inflammation from infection in both gram—and gram +, broad sensitivity	[146,147]
	D-[methyl-¹¹C] methionine	No		Incorporation into the peptidoglycan	Not applied clinically	[146,147]
	D-5-[¹¹C] glutamine	No		Incorporation into the peptidoglycan	Highly specific, high sensitivity for gram +, no uptake in sterile inflammation, fast clearance	[148]
	D-5-[¹¹C] glutamine	No		Incorporation into the peptidoglycan	Corroborating studies needed, not yet applied clinically	[148]
Vitamin Uptake	¹²⁴I-fialuridine (FIAU)	Yes	Endogenous TK enzyme of pathogenic bacteria	Trapped in the cell after phosphorylation	Reduced uptake in the presence of metal artifacts,	[154,168,169]
	¹²⁴I-fialuridine (FIAU)	Yes	Endogenous TK enzyme of pathogenic bacteria	Trapped in the cell after phosphorylation	More clinical studies needed to assess clinical efficacy	[154,168,169]
	¹¹¹In-biotin	No	Production of Fatty Acid	Bacterial growth factor	Essential growth factor for S. aureus	[149]
	¹¹¹In-biotin	No	Production of Fatty Acid	Bacterial growth factor	Corroborating in vivo studies needed to assess clinical relevance	[149]
	^99mTc-PAMA	No	Vitamin B12 Metabolism	Vitamin B12 derivative that accumulates in rapidly proliferating cells	High uptake in Gram + and Gram -	[150]
	^99mTc-PAMA	No	Vitamin B12 Metabolism		Not applied clinically	[150]
	¹⁸F or ³H-PABA	No	Folic Acid Synthesis	Inhibition of Thymidine Synthesis	Accumulation in MRSA and other resistant organisms	[151]
	¹⁸F or ³H-PABA	No	Folic Acid Synthesis	Inhibition of Thymidine Synthesis	In vivo studies needed	[151]
Polyclonal Antibodies	⁶⁴Cu-NODAGA	No	Membrane protein binding of polyclonal antibody	Microbe-specific membrane polyclonal antibody binding	Particular to a specific microbe	[164,165]
Polyclonal Antibodies	⁶⁴Cu-NODAGA	No	Membrane protein binding of polyclonal antibody	Microbe-specific membrane polyclonal antibody binding	Slow accumulation time	[164,165]
Siderophores	⁶⁸Ga-FOXE	No	Iron Transport	Accumulation of Siderophores in the cell	High uptake in S. aureus and fungi	[160,161,162]
Siderophores	⁶⁸Ga-FOXE	No	Iron Transport	Accumulation of Siderophores in the cell	Not used in DFI model	[160,161,162]
Immunoscintigraphy	^99mTc-sulesomab	Yes	WBC migration to infectious foci	Binds to antigen-90 on WBC membranes	Ease of preparation? Not sure about this	[63,71]
	^99mTc-sulesomab			Binds to antigen-90 on WBC membranes	Dependent upon host response, expensive, limited availability	[63,71]
	^99mTc-Besilesomab			Binds to antigen-95 on granulocytes and their precursors	Ease of preparation, good sensitivity and specificity	[63]
	^99mTc-Besilesomab			Binds to antigen-95 on granulocytes and their precursors	Dependent upon host response, expensive, limited availability	[63]

Table adapted from Ankrah et al. (2018) [131].