Longitudinal amyloid imaging using 11C-PiB: methodologic considerations.
Several methods are in use for analyzing (11)C-Pittsburgh compound-B ((11)C-PiB) data. The objective of this study was to identify the method of choice for measuring longitudinal changes in specific (11)C-PiB binding.


METHODS
Dynamic 90-min (11)C-PiB baseline and follow-up scans (interval, 30 ± 5 mo) were obtained for 7 Alzheimer disease (AD) patients, 11 patients with mild cognitive impairment (MCI), and 11 healthy controls. Parametric images were generated using reference parametric mapping (RPM2), reference Logan values, and standardized uptake value volume ratios (SUVr), the latter for intervals between 60 and 90 (SUVr(60-90)) and 40 and 60 (SUVr(40-60)) minutes after injection. In all analyses, cerebellar gray matter was used as a reference region. A global cortical volume of interest was defined using a probability map-based template. Percentage change between baseline and follow-up was derived for all analytic methods.


RESULTS
SUVr(60-90) and SUVr(40-60) overestimated binding with 13% and 10%, respectively, compared with RPM2. Reference Logan values were on average 6% lower than RPM2. Both SUVr measures showed high intersubject variability. Over time, R1, the delivery of tracer to the cortex relative to that to the cerebellum, decreased in AD patients (P < 0.05) but not in MCI patients and controls. Simulations showed that SUVr, but not RPM2 and reference Logan values, was highly dependent on uptake period and that changes in SUVr over time were sensitive to changes in flow.


CONCLUSIONS
To reliably assess amyloid binding over time--for example, in drug intervention studies--it is essential to use fully quantitative methods for data acquisition and analysis.
Department of Nuclear Medicine and PET Research, VU University Medical Center, Amsterdam, The Netherlands. b.berckel@vumc.nl
Bart N M
BN
van Berckel
Rik
R
Ossenkoppele
Nelleke
N
Tolboom
Maqsood
M
Yaqub
Jessica C
JC
Foster-Dingley
Albert D
AD
Windhorst
Philip
P
Scheltens
Adriaan A
AA
Lammertsma
Ronald
R
Boellaard
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D052160:Benzothiazoles / Q000493:pharmacokinetics*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013844:Thiazoles; D014018:Tissue Distribution
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D015415:Biomarkers; D019275:Radiopharmaceuticals; D013844:Thiazoles
11C-Pittsburgh compound-B; Alzheimer disease; SUVr; positron emission tomography; receptor parametric mapping; reference Logan