Table 1.
Summary of the four currently most used and tested 2-nitroimidazole hypoxia positron-emission tomography (PET) tracers ([18F]-FMISO, [18F]-FAZA, [18F]-FETNIM, [18F]-HX4), and how these compare to the characteristics of the ideal hypoxia PET tracer.
| Characteristic | Tracer | ||||
|---|---|---|---|---|---|
| [18F]-FMISO | [18F]-FAZA | [18F]-FETNIM | [18F]-HX4 | ||
| 1 | Hypoxia specificity | [5,12,13] | [5] | [5] | [5,6] |
| 2 | Well-defined mechanism of retention | [14] | [15] | [16] | [4] |
| 3 | Homogenous distribution and rapid clearance | [5] | [5] | [5] | [4,5,6] |
| 4 | Little dependency on factors that co-vary with hypoxia | [17] | [18] | [19] | [20] |
| 5 | Stability against non-hypoxic metabolism | [6,21] | x | x | [6] |
| 6 | Suitable acquisition time | [22] | [23] | [23] | [23] |
| 7 | Easy to synthesize and readily available | [24] | [24] | [24] | [24,25] |
| 8 | Amenable dosimetry profile | [5,26] | [5] | [26] | [26] |
| 9 | Repeatability spatial uptake | [27] | [28] | [29] | [30] |
| 10 | Effective regardless of tumor type and stage | [5] | [5] | [5] | [5] |
Green: characteristic met; yellow: no consensus; red: characteristics not met; gray: no data available. Definition of characteristics: (1) the tracer should be retained in regions with hypoxia within the clinically relevant range; (2) the mechanism of cellular retention should be well-defined and independent of cell type; (3) the tracer should be sufficiently lipophilic to enter cells and allow uniform tissue distribution, but also sufficiently hydrophilic to avoid membrane sequestration, and have faster clearance from systemic circulation and normoxic tissue; (4) its pharmacokinetic profile and tissue distribution should exhibit little dependence on parameters that may co-vary with hypoxia, such as blood flow or pH; (5) it should have high stability against non-hypoxia specific metabolism in vivo; (6) its tissue kinetics should be suitable for imaging within a timeframe permitted in the clinical setting; (7) it should be easy to synthesize and readily available; (8) it should possess a favorable radiation dosimetry profile; (9) it should be repeatable to allow both detection of hypoxia and return to normoxia; (10) it should be effective in multiple tumor types and stages.