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 |