Table 3 PET imaging biomarkers for assessment of the immune and tumor environment of gliobastoma
Hallmark | Threshold | Advantages | Limitations |
|---|---|---|---|
Cellular proliferation | ↑18F-FLT | Correlated to Ki-67 High sensitivity (nM) Absolute quantification | Does not cross the intact blood-brain barrier (BBB) High cortical background activity Low specificity Challenging production |
Membrane proliferation | ↑18F-choline | High sensitivity (nM) Absolute quantification Radiation necrosis vs. recurrence | Does not cross the intact BBB Inflammation vs. Tumor tissue High cortical background activity Availability |
Structural complexity | – | – | – |
Aminoacid metabolism | ↑11C-methionine ↑18F-FET ↑18F-FDOPA | Cross the intact BBB Specificity | Half-life (11C- methionine = 20 min) Availability |
Glucose metabolism | ↑18F-FDG | Availability Cross the intact BBB No side effects | High cortical background activity Non-specific: inflammation vs. tumor |
Angiogenesis | ↑18F-RGD | Marker for αVβ3 expression | Primarily an experimental application |
Perfusion | ↑15O-H2O | Quantification in mL/100 g per min | Availability Time and cost consuming |
Invasiveness | – | – | – |
Hypoxia | ↑18F-FMISO ↑18F-FAZA ↓15O-H2O | Identification of radiation resistant areas | Primarily experimental application |
Necrosis | – | – | – |
Edema | – | – | – |
Infiltration of cytotoxic T cells | ↑18F-FHBG | Track HSV1-tk reporter gene expression (cytotoxic T cells) | Preclinical experimental application |
↑ 89Zr-PEGylated-anti-CD8-VHH | Track CD8+ T cells | Primarily experimental application | |
↑68Ga-DOTA-D-Phe1-Tyr3-Octreotide | Activated immune cells | Primarily experimental application | |
Anergy of T cells | ↑PD-1 or PD-L1 | Prediction of the effectiveness of anti-PD1 | Still experimental on mouse tumor models |
Activated microglia | ↑TSPO (immuno-PET) | Nonspecific: tumor vs. neuro-inflammation |