Imaging cell death and treatment response | 18F-FDG | PET | Transported via glucose transporterPhosphorylated by hexokinase Measure of glucose utilization, glycolysis, and tumor cellularity | Leading PET tracerIn routine clinical use Used for staging, monitoring treatment response, and detection of recurrence Can be used as specific biomarker of therapy response; for example, tyrosine kinase inhibition with imatinib | (14) |
| [1-13C]pyruvate | DNP | Transported by monocarboxylate transporter Converted by lactate dehydrogenase into lactate Lactate signal dependent on endogenous lactate concentration as well as enzyme and coenzyme concentrations | Leading DNP substrate Preclinical marker of treatment response and tumor grade Clinical trials are beginning Can be used as specific biomarker of therapy response; for example, PI3K pathway inhibition | (6,7,10,15,16) |
| 18F-annexin | PET | Binds to phosphatidylserine expressed on surface of apoptotic cells Also binds to phosphatidylserine on inner leaflet of plasma membrane bilayer during necrosis | Measures cell death Potential for early tumor detection and response to treatment | (17) |
| 18F-isatin sulfonamide | PET | Binds to activated caspase-3/7 | Measure of apoptosis Potential for early tumor detection and response to treatment Currently undergoing clinical trials | (18) |
| [1,4,-13C2]fumarate | DNP | Hydrated by fumarase to form malate Transported into cell slowly, so significant metabolism is observed only in necrotic cells that have compromised plasma membrane integrity No coenzymes required | Noninvasive marker of necrosis in vitro and in vivo Marker of treatment responseLow background signalNo clinical data | (19,20) |
Imaging proliferation and cell growth | 3′-deoxy-3′-18F-fluorothymidine | PET | Thymidine analog Phosphorylated by thymidine kinase 1 Detects dividing cells | Marker of DNA synthesis and cell proliferation Potential for early detection of tumor response to treatment Kinetic modeling is required Ongoing multicenter clinical trials | (21) |
| [5-13C]glutamine | DNP | Converted by intramitochondrial glutaminase into glutamate | Marker of glutamine metabolism, which may reflect cell proliferation Limited by short half-life of polarization and relatively slow metabolism | (22) |
Imaging pH and hypoxia | 18F-fluoromisonidazole | PET | Nitroimidazole derivative Undergoes reduction and cellular trapping in hypoxic conditions | Marker of hypoxia | (23) |
| 64Cu-diacetyl-bis(N4-methylthiosemicarbazone) | PET | Reduction of Cu(II) to Cu(I) occurs in both normoxia and hypoxia but remains as Cu(I) in hypoxic conditions Cu(I)-ATSM is charged and trapped inside cell | Marker of hypoxia Potential marker of tumor aggressiveness Ongoing clinical trials Potential for use in radionuclide therapy | (23) |
| [1-13C]pyruvate | DNP | See above | May report indirectly on hypoxia-inducible factor-1 (HIF-1) | (24) |
| 13C-labeled bicarbonate | DNP | H13CO3− exchanges with 13CO2 rapidly, and ratio of the two is a measure of pH Exchange is almost instantaneous in presence of carbonic anhydrase | Measures extracellular pH predominantly | (8) |
| 64Cu pH low-insertion peptide | PET | Inserts into plasma membrane in presence of acidic extracellular environment | Measures relative extracellular pH | (5) |