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Table 3 PET imaging biomarkers for assessment of the immune and tumor environment of gliobastoma

From: Imaging-guided precision medicine in glioblastoma patients treated with immune checkpoint modulators: research trend and future directions in the field of imaging biomarkers and artificial intelligence

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
  1. 18F-FLT 18F-fluorothymidine, BBB blood-brain barrier, 18F-FDG 18F-fluorodeoxyglucose, 18F-FET 18F-fluoroethyltyrosine, 11C-MET 11C-methionine, 18F-RGD 18F-arginine-glycine-aspartic acid, 18F-FMISO 18F-fluoromisonidazole, 18F-FHBG 18F-fluoro-3-(hydroxymethyl)butylguanin, ↓ decrease, ↑ increase