The deposition of β-amyloid protein within cortical regions of the brain is a pathologic hallmark of Alzheimer disease that is believed to precede clinical symptoms by several years.
13 This feature of the disease makes in vivo imaging of β-amyloid in the brain of particular interest for the identification of individuals at risk for, and in the early stages of, Alzheimer disease (
Figure 2).
Quantification of amyloid deposition in the brain with neutrally charged derivatives of thioflavin-T was initially developed at the University of Pittsburgh School of Medicine in Pennsylvania.
14,15 The marker selected for optimal amyloid detection—N-methyl-[
11C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole—was named Pittsburgh Compound B (PiB) and is used in conjunction with positron emission tomography (PET) for in vivo identification of cortical amyloid burden.
15 This technique is widely known as PiB PET imaging.
This type of imaging has been reliably validated as an effective method for quantifying amyloid deposition within specific brain regions. It is especially useful and effective for discriminating between Alzheimer disease and other forms of dementia.
16 Antiamyloid therapies, such as AN1792 vaccine or bapineuzumab antibody, that are designed to reduce amyloid accumulation involve the use of PiB PET imaging to monitor efficacy of treatment.
17
The detection of increased amyloid burden with PiB PET imaging has been reported as a means of identifying individuals with mild cognitive impairment (MCI) who are at increased risk of progression to Alzheimer disease.
17,18 In addition, increased amyloid deposition has been linked to reduced volume of the hippocampus and to episodic memory loss.
19 However, a number of recent studies have documented high proportions of cognitively normal individuals with amyloid accumulation on the order of levels observed in patients with Alzheimer disease.
20,21
Furthermore, there is a logistical concern over using PiB PET imaging to analyze amyloid deposition. The short radioactive half-life (20 minutes) of the
11C (carbon-11) label necessitates either the use of an on-site cyclotron or the rapid shipment of labeled substrate and very tight scheduling of patients to be imaged. This limitation has led to the search for more stable compounds that could be used in conjunction with PET imaging—such as compounds labeled with
18F (fluorine-18) rather than
11C. The most recently identified of these compounds is
18F-AV-45—(E)-4-(2-(6-(2-(2-(2-([
18F]-fluoroethoxy)ethoxy) ethoxy)pyridin-3-yl)vinyl)-N-methyl benzenamine, though a number of other compounds exist, including
18FFDDNP—[
18F] 1,1-dicyano-2-[6-(dimethylamino)-2-naphtalenyl] propene.
17,22,23 The half-life of
18F-AV-45 is on the order of 110 minutes, allowing for remote synthesis and shipment of the radio-labeled probe across moderate distances.