title: Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound-B.
abstract: A valid quantitative imaging method for the measurement of amyloid deposition in humans could improve Alzheimer's disease (AD) diagnosis and antiamyloid therapy assessment. Our group developed Pittsburgh Compound-B (PIB), an amyloid-binding radiotracer, for positron emission tomography (PET). The current study was aimed to further validate PIB PET through quantitative imaging (arterial input) and inclusion of subjects with mild cognitive impairment (MCI). Pittsburgh Compound-B studies were performed in five AD, five MCI, and five control subjects and five subjects were retested within 20 days. Magnetic resonance images were acquired for partial volume correction and region-of-interest definition (e.g., posterior cingulate: PCG; cerebellum: CER). Data were analyzed using compartmental and graphical approaches. Regional distribution volume (DV) values were normalized to the reference region (CER) to yield DV ratios (DVRs). Good agreement was observed between compartmental and Logan DVR values (e.g., PCG: r=0.89, slope=0.91); the Logan results were less variable. Nonspecific PIB retention was similar across subjects (n=15, Logan CER DV: 3.63+/-0.48). Greater retention was observed in AD cortical areas, relative to controls (P<0.05). The PIB retention in MCI subjects appeared either 'AD-like' or 'control-like'. The mean test/retest variation was approximately 6% in primary areas-of-interest. The Logan analysis was the method-of-choice for the PIB PET data as it proved stable, valid, and promising for future larger studies and voxel-based statistical analyses. This study also showed that it is feasible to perform quantitative PIB PET imaging studies that are needed to validate simpler methods for routine use across the AD disease spectrum.
authors.affiliation: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. pricejc@upmc.edu
authors.forename: Julie C
authors.initials: JC
authors.lastname: Price
authors.forename: William E
authors.initials: WE
authors.lastname: Klunk
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lopresti
authors.forename: Xueling
authors.initials: X
authors.lastname: Lu
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Hoge
authors.forename: Scott K
authors.initials: SK
authors.lastname: Ziolko
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Holt
authors.forename: Carolyn C
authors.initials: CC
authors.lastname: Meltzer
authors.forename: Steven T
authors.initials: ST
authors.lastname: DeKosky
authors.forename: Chester A
authors.initials: CA
authors.lastname: Mathis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D000682:Amyloid / Q000378:metabolism; D000814:Aniline Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002525:Cerebellar Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007700:Kinetics; D008297:Male; D008569:Memory Disorders / Q000000981:diagnostic imaging / Q000378:metabolism; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding; D011859:Radiography; D013844:Thiazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000682:Amyloid; D000814:Aniline Compounds; D013844:Thiazoles