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 |