Limitations of Nonamyloid PET Biomarkers for AD
A majority of PET radiotracers targeting nonamyloid processes are labeled with carbon-11 (11-C), which stands as a limitation owing to the short (~20 min) half-life of this isotope. Production of 11-C radioligands is therefore limited to imaging centers possessing an onsite cyclotron and a radiochemistry department with the requisite expertise, making the cost of studies prohibitive for routine clinical use. Though fluorine-18 radiopharmaceuticals have been introduced-with a half-life of approximately 110 min allowing for centralized production and regional distribution-only [F]FDG is currently approved for clinical use. In the case of TSPO ligands, their clinical utility may further be hampered by differential binding affinity among carriers of a common single-nucleotide polymorphism (rs6971) in exon 4 of the TSPO gene. The issue of specificity for AD likewise stands as a limitation owing to the presence of neuroinflammation, deposition of hyperphosphorylated tau, dysregulation of neurotransmitter systems and hypometabolic changes across a wide range of neurodegenerative diseases (for review, see).