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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