Cerebellum can serve as a pseudo-reference region in Alzheimer’s disease to detect neuroinflammation measured with PET radioligand binding to translocator protein (TSPO)

摘要

Alzheimer’s disease (AD) is associated with increase in brain of the 18 kDa translocator protein (TSPO), which is over-expressed in activated microglia and reactive astrocytes. Measuring the density of TSPO with PET typically requires absolute quantitation with arterial blood sampling, because a reference region devoid of TSPO does not exist in brain. We sought to determine whether a simple ratio method could substitute for absolute quantitation of binding with ¹¹C-PBR28, a second generation radioligand for TSPO.Methods¹¹C-PBR28 PET imaging was performed in 21 healthy controls, 11 individuals with mild cognitive impairment (MCI), and 25 AD patients. Group differences in ¹¹C-PBR28 binding were compared using two methods. First, the “gold standard” method of calculating total distribution volume (VT), using the two-tissue compartmental model with the arterial input function, corrected for plasma free fraction of radiotracer (fP). Second, a ratio of brain uptake in target regions to that in cerebellum—i.e., standardized uptake value ratio (SUVR).