Table 2 Overview (non-exhaustive) and development status of novel PET radiotracers for TB imaging
From: PET imaging of mycobacterial infection: transforming the pipeline for tuberculosis drug development
Tracer name | MoA / cellular target | Status | Key notes | Role as anti-MTb drug efficacy PET-biomarker |
|---|---|---|---|---|
[68Ga]Ga-DN393 | Tuberculoma hypoxia | CS | Visualization of hypoxia in a few patients with active TB (low sensitivity) | n.d. |
[64Cu]Cu-ATSM94 | Tuberculoma hypoxia | PC | Appropriate imaging of the necrotic tuberculoma microenvironment | + |
[18F]Sodium fluoride95 | Tissue micro-calcification caused by MTb tissue pathology | PC | Accurate detection of tissue pathology due to Mtb manifestation | ++ |
Inhibits fibroblast-activated protein in tuberculoma cells | CS | Sensitive visualization of pulmonary TB lesion (not TB specific) | n.d. | |
[18F]FDT99 | MTb-specific cell wall uptake via the trehalose pathway | PC | Accurate visualization of pulmonary TB lesion (sensitivity equal to [18F]FDG-PET) | ++ |
[68Ga]Ga-UBI29-41100 | Antimicrobial peptide for bacteria-specific targeting of the cell wall | PC / CS | Accurate visualization of pulmonary TB and EPTB | n.d. |
[64Cu]Cu-LL2PA101 | Peptidomimetic ligand targeting -VLA-4 (α4β1) -expressing cells in tuberculomas | PC | Improved specificity for TB, tracer uptake driven by Mφ and T-cells | _ |
Modified peptidetargeting formyl peptide receptor 1 expressed on tuberculoma cells | PC | Accurate imaging of MTb-associated inflammation, uptake driven by neutrophils (appropriate sensitivity) | n.d. | |
[18F]ICMT-11104 | Isatin-containing tracer, specific to caspase-3/7 expressed on Mφ | PC | Accurate PET imaging of caspase-3/7-specific activity during cell apoptosis (cisplatin-induced) in tuberculoma | ++ |
[11C]JNJ-28312141105 | Binds to colony-stimulating factor 1 receptor expressed on Mφ -crucial during TB infection | PC | Effectively delineating granulomatous foci of TB | + |
Binds to TSPO expressed on Mφ during TB infection | ECI /PC | Accurate, sensitive, and more specific imaging of MTb-associated inflammation (compared to FDG) | ++ | |
[68Ga]Ga-puromycin108 | Measures increased protein biosynthesis | PC | Accurate visualization of BCG-based lung pathology (low sensitivity) | + |
2-[18F]INH109 | MTb-specific pro-drug (blocks type II fatty acid synthase) | PC | Accurate and sensitive visualization of pulmonary TB lesion (slow PK, moderate sensitivity) | _ |
5-[18F]F-PZA110 | MTb-specific drug derivative (activated by pyrazinamidase) | PC | Accurate visualization of pulmonary TB (enzyme inhibitor with low sensitivity) | _ |
[18F]Pretomanid83 | Inhibiting mycolic acid biosynthesis | PC/ FIH | Favorably low pulmonary uptake and radiation dosimetry FIH; high uptake in a TB meningitis model (mycobacteria-selective) | ++ |
Anti-tubercular enzymatic antifolate action | PC/ FIH | MoA prevalent in MTb. Favorably low pulmonary uptake and radiation dosimetry FIH. Not mycobacteria-specific | ++ | |
Imaging of bacterial TK-1 expression via metabolic cell entrapment | PC/FIH | Favorably low pulmonary uptake and radiation dosimetry FIH; appropriate in vivo sensitivity (not bacteria-selective) | ++ |
