Validation of the Semiquantitative Static SUVR Method for F-AV45 PET by Pharmacokinetic Modeling with an Arterial Input Function.

Increased brain uptake of F-AV45 visualized by PET is a key biomarker for Alzheimer disease (AD). The SUV ratio (SUVR) is widely used for quantification, but is subject to variability based on choice of reference region and changes in cerebral blood flow. Here we validate the SUVR method against the gold standard volume of distribution (V) to assess cross-sectional differences in plaque load. Dynamic 60-min F-AV45 (291 ± 67 MBq) and 1-min O-HO (370 MBq) scans were obtained in 35 age-matched elderly subjects, including 10 probable AD, 15 amnestic mild cognitive impairment (aMCI), and 10 cognitively healthy controls (HCs). F-AV45 V was determined from 2-tissue-compartment modeling using a metabolite-corrected plasma input function. Static SUVR was calculated at 50-60 min after injection, using either cerebellar gray matter (SUVR) or whole subcortical white matter (SUVR) as the reference. Additionally, whole cerebellum, pons, centrum semiovale, and a composite region were examined as alternative references. Blood flow was quantified by O-HO SUV. Data are presented as mean ± SEM. There was rapid metabolization of F-AV45, with only 35% of unchanged parent remaining at 10 min. Compared with V, differences in cortical Aβ load between aMCI and AD were overestimated by SUVR (+4% ± 2%) and underestimated by SUVR (-10% ± 2%). V correlated better with SUVR (Pearson r: from 0.63 for posterior cingulate to 0.89 for precuneus, < 0.0001) than with SUVR (Pearson r: from 0.51 for temporal lobe [ = 0.002] to 0.82 for precuneus [ < 0.0001]) in all tested regions. Correlation results for the alternative references were in between those for CB and WM. O-HO data showed that blood flow was decreased in AD compared with aMCI in cortical regions (-5% ± 1%) and in the reference regions (CB, -9% ± 8%; WM, -8% ± 8%). Increased brain uptake of F-AV45 assessed by the simplified static SUVR protocol does not truly reflect Aβ load. However, SUVR is better correlated with V and more closely reflects V differences between aMCI and AD than SUVR.