Original Article
Journal of Cerebral Blood Flow & Metabolism (2005) 25, 1528–1547. doi:10.1038/sj.jcbfm.9600146; published online 8 June 2005
Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound-B
This work was supported by NIH, R01 AG018402, P50 AG005133, K02 AG001039, R01 AG020226, R01 MH070729, K01 MH001976, Alzheimer's Association (TLL-01-3381), US Department of Energy (DE-FD02-03 ER63590), and GE Healthcare. GE Healthcare (formerly Amersham Health) (Chalfont St Giles, UK) provided research grant support and entered into a License Agreement with the University of Pittsburgh based on the technology described in this manuscript. Drs Klunk and Mathis are coinventors of PIB and, as such, have a financial interest in this license agreement.
Julie C Price1, William E Klunk2, Brian J Lopresti1, Xueling Lu1, Jessica A Hoge1, Scott K Ziolko1, Daniel P Holt1, Carolyn C Meltzer1, Steven T DeKosky3 and Chester A Mathis1
- 1Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- 2Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- 3Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Correspondence: Dr JC Price, Department of Radiology, University of Pittsburgh, PET Facility, 200 Lothrop Street, Rm. B-938, Pittsburgh, PA 15213, USA. E-mail: pricejc@upmc.edu
Received 23 November 2004; Revised 25 March 2005; Accepted 25 March 2005; Published online 8 June 2005.
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
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.
Keywords:
Alzheimer's disease, amyloid beta-protein, kinetic modeling, mild cognitive impairment, PET
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