Radiotracers Used for the Scintigraphic Detection of Infection and Inflammation

Table 5

Applications of selected radiotracers.

Radiotracer molecules	In vitro experiments	Type of model/animal		Human; use	Uptake mechanism in vivo	Application as a potential nuclear diagnostic agent
		Infection	Inflammation
Synthetics
^111In-fMLFK	fMLF BA, superoxide release by PMN	S. aureus/rats	−	?		−
^99mTc-fMLFK		E. coli, S. aureus/rabbits	Zymosan/rabbit	?	Chemotactic peptide binds to PMN & monocytes	−
^99mTc-MLF-OMe				?		−
^68Ga-citrate	—	—	−	+	^68Ga-transferrin forms in circulation, binds to lactoferrin in LEuK or ferritin/siderophores in pathogens	100% sensitivity, 76% specificity in bone infections
^68Ga-TAFC & ^68Ga-FOXE	Fungal BA, in vivo binding	Aspergillus fumigatus/rats	−	−	Uptake by pathogens via Fe transporter system	A. fumigatus (fungus) specific
^111In-LTB-4 (DPC11870-11)	Receptor BA	E. coli/rabbits	TNBS colitis/rabbit	?	LT INF mediator participates in lipoxygenase pathway & binds to PMN after migration from bone marrow to abscess	+
^99mTc-LTB-4 (MB88) & ^18F-LTB-4 (MB67)	—		−	?		+
Antibiotics
^99mTc-fluconazole	Microbe/leukocyte BAs	C. albicans,  A. fumigatus/mice	−	?	↓ fungal cytochrome P450 enzyme 14-demethylase	Fungal specific
^99mTc-ciprofloxacin	Bacteria BA	C. albicans, S. aureus/rats	Turpentine/rats	+	Binding bacterial DNA gyrase	94% sensitivity, 83% specificity in orthopedic infections
^99mTc-enrofloxacin				?		+
^99mTc-pefloxacin	—	S. aureus/rats	−	?	↓ type II topoisomerase DNA gyrase	+
^99mTc-ceftizoxime	Antimicrobial assay	E. coli/rats	−	?	↓ peptidoglycan biosynthesis & binding to bacterial membrane	+
^99mTc-vancomycin	—	S. aureus/rats	Turpentine/rats	?	↓ cell wall biosynthesis in gram +ve bacteria & binding to membrane	+
^99mTc-kanamycin	Bacteria BA	S. aureus/rats, rabbits	−	?	↓ protein synthesis & binding to 30S subunit of prokaryotic ribosome	+
^99mTc-alafosfalin	Bacteria BA	S. aureus/rats, mice	TNBS colitis/rats	−	↓ peptidoglycan biosynthesis	−
^99mTc-phosphomycin	—	E. coli, S. aureus/mice	−	−	↓ bacterial cell wall biosynthesis & inactivating UDP-N-acetylglucosamine-3-enolpyruvyltransferase	−
^99mTc-cefoperazone	—	S. aureus/rats	Turpentine/rats	?	↓ cell wall biosynthesis	+
^99mTc-cefuroxime axetil	—	S. aureus/rats	Turpentine/rats	?	↓ cell wall biosynthesis & binding to essential target proteins	+
^99mTc-novobiocin	—	S. aureus/rats	−	−	↓ bacterial DNA gyrase & targeting enzyme GyrB subunit	?
Biological origin
Cells:
^18FDG-leukocytes	Radiolabeling & purification	P. aeruginosa, E. coli/rats	Turpentine/rats	+	Participates in INF response	84% accuracy, in suspected infection
^111In-lymphocytes		—	+	+	Participates in INF, LYM graft trapping	Diagnosis of acute kidney-graft rejection
^111In-dendritic cells	DC phenotype & viability	Allogenic antigens/sheep		−	Participates in INF response, DC traffic to local lymph nodes to interact with T-LYM	−
Macromolecules:
^111In-DTPA-hpc-IgG	—	E. coli, S. aureus, P. aeruginosa, K. pneumonia, C. albicans/rats	Turpentine/rats	+	VP, transchelation ^111In to extravascular proteins	100% sensitivity, 85% specificity chronic osteomyelitis, spondylodiscitis, pulmonary INF
^99mTc-HYNIC-hpc-IgG	Histopathology	S. aureus, P.	Turpentine/mice	+	VP, ^99mTc binds to local tissue
Macromolecules:
^99mTc-hpc-IgG	—	S. aureus/rats	−	+	VP, Fc receptor binding to local INF cells	Scintigraphic staging of IBD patients
^99mTc-rat pc-IgG			−	−		Species specific marker
^99mTc-HSA	—	E. coli, S. aureus, P. aeruginosa, K. pneumonia, C. albicans/rats	Turpentine/rats	−	VP, no receptors for retention	Capillary permeation marker
^99mTc-infliximab	TNF BAs	S. aureus/rats	−	+	Participating in granule release pathway, specific binding to ↑ h-TNF pro-INF cytokine	In patients with refractory monoarthritis, not IBD
^99mTc-fanolesomab	—	—	−	+	Specific binding to 3-fucosyl-N-acetyl-lactosamine in CD15 antigens expressed by h-PMN & eosinophils	Withdrawn from market
^99mTc-E-Selectin peptide (IMP-178)	BAs	—	Osteomyelitis, arthritis/rat	?	Specific binding to E-selectin (CD62E) expressed on endothelium, ↑ in RA	+
^123I-B2702-p (75–84) & ^99mTc-B2702-p (+his-gly)	Immunohistochemistry, autoradiography	—	Artherosclerotic plaques/rabbits	−	Specific binding to ↑ VCAM-1 expressed by vulnerable plaques	+
^99mTc-PEG-liposomes	Histopathology	S. aureus, P. Aspergillus/rats	Turpentine/mice	+	“physiologic filtration” rather than phagocytosis	Side effects [100]
^123I-hr-IL-1 & ^123I-hr-IL-1	EL-4 BA	S. aureus/mice, E. Coli/rabbits	−	?	Participating in granule release pathway, specific binding to IL-1 receptors expressed on LEUK	?
^18F-hr-IL-1ra	—	Biodistribution/normal rats		−		+
^99mTc-IL-18bp-Fc-IL-1ra	BAs	—	Ear edema/mice	?	Specific binding to IL-1 receptors expressed on PMN & IL-18	+
^99mTc-HYNIC-IL-2	CD25 BA	—	−	+	Participating in granule release pathway, specific binding to IL-2 receptors (CD25) by tissue infiltrating LYM	100% sensitivity, inflamed atherosclerotic plaque,
^123I-hr-IL-2	—	—	−	+		assess influx of mononuclear cells within gut wall in CD
^18F-hr-IL-2	BA	Active T-LYM in Matrigel/immune-incompetent; SCID mice		?	Participating in granule release pathway & bindins to human activated T-LYM expressing CD25	Detect cell migration in autoimmune diseases, & graft rejection
^99mTc-hr-IL-8	—	A. Fumigatus, lung infection/rabbits	−	+	Participating in granule release pathway, specific binding to IL-8 receptors (CXCR1, CXCR2) expressed by PMN	Early detection of infections/INFs
^99mTc-HYNIC-IL-12	Receptor BA	—	Autoimmune colitis	?	Participating in granule release pathway, specific binding to IL-12 receptors on activated T or NK LYM	In vivo imaging of T-LYM in immune-mediated processes
^99mTc-HYNIC-C5a & ^99mTc-HYNIC-C5adR	Receptor BA	E. coli/rabbits	−	−	INF mediator in complement pathway binds to guanine nucleotide-binding inhibitory protein receptors	−
Smaller fragments:
^99mTc-UBI-29-41	BA	Bacterial, C.  albicans/mice, rabbits	Saline, LPS, dead bacteria or C. albicans/mice	+	Antimicrobial peptide fragment that is trapped in the cell membrane of microorganisms	100% sensitivity, 80% specificity, infective foci in bone, soft tissue
^99mTc-HYNIC-UBI-29-41	Bacteria BA	S. aureus/mice	−			+

PMN: polymorphonuclear neutrophils; LT: leukotriene; ?: no recent reports; h: human; DC: dendritic cells; pc: polyclonal; IL: interleukin; r: recombinant; IBD: inflammatory bowel disease; CD: Crohn’s disease; LPS: lipopolysaccharide; TNBS: 2,4,6-trinitrobenzene sulfonic acid (to induce experimental colitis); INF: inflammatory; RA: rheumatoid arthritis; LEuK: leukocytes; VP: vascular permeability; LYM: lymphocytes; BA: binding assay; ↑: increases; ↓: inhibits.