METHODS: (11)C-PBR28 PET imaging was performed in 21 healthy controls, 11 individuals with mild cognitive impairment, and 25 AD patients. Group differences in (11)C-PBR28 binding were compared using 2 methods. The first was the gold standard method of calculating total distribution volume (V(T)), using the 2-tissue-compartment model with the arterial input function, corrected for plasma-free fraction of radiotracer (f(P)). The second method used a ratio of brain uptake in target regions to that in cerebellum-that is, standardized uptake value ratio (SUVR).
RESULTS: Using absolute quantitation, we confirmed that TSPO binding (V(T)/f(P)) was greater in AD patients than in healthy controls in expected temporoparietal regions and was not significantly different among the 3 groups in the cerebellum. When the cerebellum was used as a pseudo-reference region, the SUVR method detected greater binding in AD patients than controls in the same regions as absolute quantification and in 1 additional region, suggesting SUVR may have greater sensitivity. Coefficients of variation of SUVR measurements were about two-thirds lower than those of absolute quantification, and the resulting statistical significance was much higher for SUVR when comparing AD and healthy controls (e.g., P < 0.0005 for SUVR vs. P = 0.023 for VT/fP in combined middle and inferior temporal cortex).
CONCLUSIONS: To measure TSPO density in AD patients and control subjects, a simple ratio method SUVR can substitute for, and may even be more sensitive than, absolute quantitation. The SUVR method is expected to improve subject tolerability by allowing shorter scanning time and not requiring arterial catheterization. In addition, this ratio method allows smaller sample sizes for comparable statistical significance because of the relatively low variability of the ratio values.