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Table 2 PET biomarkers for neurodegenerative diseases

From: Relevance of biomarkers across different neurodegenerative diseases

Biomarker Target Advantages Disadvantages
18F-FDG Glucose metabolism Capable of detecting dysfunction that has not necessarily involved atrophy; well-validated for clinical research Variability in methods of analysis between studies/centers
18F-FDDNP AD lesions 18F half-life does not require on-site cyclotron Does not differentiate Aβ or tau aggregations
11C-PBB3 Tau lesions Sensitive to both AD-type tau aggregations and non-AD tau aggregations; correlates with clinical progression Short half-life of 11C; relatively low affinity compared to other tau markers; non-specific binding
18F-AV1451 (flortaucipir) Tau lesions High affinity to aggregated tau; distribution of binding reflects clinical presentations; 18F half-life does not require on-site cyclotron Off-target binding to neuromelanin and choroid plexus; poor reliability in early NFT stages; preferential binding to mixed 3R/4R tau rather than isolated 3R or 4R tau
18F-GTP1 Tau lesions Ligand binding maps to known distribution of AD-tau aggregations; 18F half-life does not require on-site cyclotron Yet to be fully validated; possible high non-specific binding in basal ganglia
18F-MK6240 Tau lesions Extremely high binding affinity to tau aggregations; good brain delivery and washout; 18F half-life does not require on-site cyclotron Likely preferential binding to mixed 3R/4R tau rather than isolated 3R or 4R tau; off-target binding to neuromelanin
18F-RO6958948 Tau lesions High binding affinity to tau aggregations; preliminary study shows longitudinal increases in AD; 18F half-life does not require on-site cyclotron Yet to be fully validated; no significant binding in 3R or 4R tauopathies
18F-THK5351 Tau lesions High binding affinity to tau over Aβ aggregations; 18F half-life does not require on-site cyclotron High non-specific retention in the subcortical white matter; high MOA-B binding
18F-THK5105 Tau lesions High binding affinity to tau over Aβ aggregations; 18F half-life does not require on-site cyclotron High non-specific retention in the subcortical white matter; inferior signal-to-background ratio
18F-THK523 Tau lesions High binding affinity to tau over Aβ aggregations; 18F half-life does not require on-site cyclotron High non-specific retention in the subcortical white matter; poor in vivo visualization of tau deposition
18F-PI2620 Tau lesions Binds to both 3R/4R mix tau and 3R tau (Pick’s disease); high binding affinity to tau over Aβ aggregations and MOA-A/MOA-B; 18F half-life does not require on-site cyclotron Yet to be fully validated
18F-PM-PBB3 Tau lesions Indication that ligand is sensitive to both AD and non-AD tauopathies; little binding to MOA-A and MOA-B; 18F half-life does not require on-site cyclotron Yet to be fully validated, particularly in non-AD tauopathies
11C-PiB Amyloid-β aggregations High affinity to fibrillar Aβ; best studied of available Aβ PET tracers Short half-life of 11C; not specific to AD amyloidosis/binds to CAA
18F-AV-45 Amyloid-β aggregations High affinity to fibrillar Aβ; 18F half-life does not require on-site cyclotron Not specific to AD amyloidosis
18F-BAY94-9172 (florbetaben) Amyloid-β aggregations High affinity to fibrillar Aβ; 18F half-life does not require on-site cyclotron Not specific to AD amyloidosis
18F-GE067 (flutemetamol) Amyloid-β aggregations High affinity to fibrillar Aβ; 18F half-life does not require on-site cyclotron Not specific to AD amyloidosis
18F-NAV4694 Amyloid-β aggregations Excellent agreement with 11C-PiB; 18F half-life does not require on-site cyclotron Not specific to AD amyloidosis
11C-UCB-J Synapses (SV2A) High affinity to protein expressed on synapses Short half-life of 11C; relatively new tracer and not well-validated in dementia populations
  1. Abbreviations: PET positron emission tomography, FTD frontotemporal dementia, MOA-B monoamine oxidase B, PiB Pittsburg Compound-B, CAA cerebral amyloid angiopathy, FDG fluorodeoxyglucose, SV2A synaptic vesicle glycoprotein 2A