Lopresti BJ, Klunk WE, Cohen A, Coleman R, Weissfeld L, Mathis CA, Price JC.
Consideration of pons normalizing region for [11C]PIB PET scans.
Human Amyloid Imaging 2011 Meeting Abstracts. 2011 Jan 15;
Introduction: Negligible levels of cerebellar (CER) fibrillar As deposits in sporadic Alzheimer's disease (AD) supports
the use of CER as reference for normalizing regional [11C]PiB retention measures. A CER reference, however,
may not be ideal for all groups, particularly eoFAD or Downfs subjects, where significant CER As deposition is a
common autopsy finding. For this reason, we examined the suitability of pons (PON) as reference region for [11C]
Methods: [11C]PiB PET was performed in 188 subjects (92 Con, 50 MCI, 46 AD) and 47 of these (21 Con, 14 MCI,
11 AD) underwent fully quantitative imaging involving 90 min dynamic scanning, arterial input function
determination, and estimation of Logan DVR outcomes (ART90). Regional SUVR 50-70 retention measures were
determined for all using CER (SUVRCER) and PON (SUVRPON) as reference. For the quantitative subjects, results of
the SUVR methods were compared to ART90.
Results: CER:plasma ratios reached a plateau of ~6 at 30 min, while PON:plasma plateau was slower and more
transient, peaking at ~12 at 50 min. Across cortical areas, SUVRCER was less biased and more highly correlated
with ART90 than SUVRPON. However, both provided similar Cohenfs effect sizes for the distinction of AD and PIB
negative Con groups (63/92 Con subjects classed as PiB- using iterative outlier method). This is attributable to
lower variance in SUVRPON outcomes despite a compressed dynamic range. PiB positivity cutoffs for SUVRPON
identified significantly more PIB+ Cons than SUVRCER cutoffs (40% vs 28%) and included some misclassification.
Conclusion: SUVRPON effectively discriminates amyloid negative controls from AD subjects and may be useful
when cerebellar data is unavailable or contraindicated. However, the transient kinetics underlying SUVRPON may
lead to less reliable subject classification at the PiB +/- interface, relative to SUVRCER.