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 14α-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. Aspergillus/rats | 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 | TNFα BAs | S. aureus/rats | − | + | Participating in granule release pathway, specific binding to ↑ h-TNFα 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-1α & 123I-hr-IL-1β | 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.