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Table 1 Summary table of typical PET tracers for neurodegeneration-related investigations discussed in this article

From: Imaging biomarkers in neurodegeneration: current and future practices

Example tracers Protocol Analysis Limitations
Glucose metabolism:
[18F]FDG
• Fasting for ~ 4 h
• Scanning 30 min after injection
• Scan typically for 0–30 min
• SUV using weight and injected dose
• SUVR using cerebellar grey matter or pons as reference regions [7]
• Hypometabolic patterns overlap between multiple neurodegenerative diseases [8,9,10]
• Still not enough evidence to support routine clinical use in the prodromal phase [93]
Aβ:
[11C]PiB
[18F]Florbetaben
[18F]Florbetapir
[18F]Flutametamol
[18F]NAV4694
Scan protocols vary between tracers; however, typically, patients are scanned 40–60 min (PiB) or 70–90 min (most [18F]-based tracers) after injection for ~ 20 min. For EANM clinical guidelines, see Minoshima et al. [94] Typical analysis will use SUVR using the cerebellum or cerebellar grey matter as the reference region [21, 31, 32] • [C11]PiB requires an on-site cyclotron
• Second-generation tracers have certain off-target binding issues as well as reduced uptake in the cortex as compared to PiB [30]
• Latest generation tracers have yet to be validated in larger cohorts
• Aβ positivity can refer to various neurodegenerative diseases [95]
Tau:
[18F]THK5351
[18F]THK5317
[18F]THK523
[11C]PBB3
[18F]Flortaucipir
[18F]RO948
[18F]MK6240
[18F]GTP1
[18F]PI2620
Scan protocols vary between tracers; however, typically, patients are scanned in the range of 50–90 min after injection for ~ 20 min [96] Most typical analyses will derive SUVR using the cerebellum, cerebellar grey matter or inferior cerebellum/cerebellar grey as the reference region [96]. • Molecular diversity of tauopathies means no single tau tracer can be used for all disorders [57]
• First-generation tracers exhibit off-target binding and subcortical white matter uptake [96, 97]
• Second-generation ligands have yet to be evaluated with regard to clinical outcomes in larger cohorts [54, 55, 96]
• Experimental and clinical validation of tau tracers in general is still required [98, 99]
SV2A:
[11C]UCB-J
[18F]UCB-H
Scan protocols are yet to be determined in more studies using SV2A PET tracers Centrum semi-ovale is most commonly used as the reference region, despite some evidence of synaptic changes [100]. Recently, also a cerebellar reference region has been suggested. • Requires replication with more patients alongside longitudinal investigation [84, 89]
• Association with other disease features (as described above) needs to be explored