IC-PL2: Amyloid imaging: Developments, challenges, future direction

Abstract

The first in vivo positron emission tomography (PET) imaging studies of amyloid-beta (Aβ) in human subjects were reported by the UCLA group in 2002 using a fluorine-18 labeled membrane dye derivative, [F-18]FDDNP, that bound preferentially to both Aβ plaques and neurofibrillary tangles (NFT) in the brains of Alzheimer's disease (AD) patients relative to elderly control subjects. Groups from Pittsburgh and Toronto followed in 2004 with literature reports of PET imaging studies in AD and control subjects using Aβ-selective carbon-11 labeled thioflavin-T ([C-11]PIB) and stilbene ([C-11]SB-11) derivatives, respectively. Researchers have sought to employ these PET agents in cross-sectional and longitudinal studies of Aβ deposition in a variety of non-invasive imaging studies in amyloid-based diseases. In addition, investigators have sought to expand the choice of Aβ-specific radioligands to include other F-18 and C-11 labeled compounds for PET imaging applications, as well as I-123 labeled agents for single photon emission computed tomography (SPECT) imaging studies. Over the past 4 years, literature reports of Aβ imaging in human subjects using PET have exploded, with more than 70 publications in a variety of subject populations. The vast majority of these studies have utilized [C-11]PIB, but the relatively short half-life of carbon-11 (20 min) has limited its distribution to about 40 specialized PET radiochemistry facilities throughout the world. The development of a more convenient, longer-lived (110 min) F-18 labeled radioligand with in vivo properties comparable to those of [C-11]PIB has been an active area of research over the past several years with some recent encouraging results. In contrast, efforts to develop a SPECT Aβ imaging agent have been largely unsuccessful. PET Aβ imaging studies have provided some important insights into the pathophysiology of amyloid deposition, particularly in mild cognitive impairment (MCI), healthy elderly controls, and familial AD subjects. Aβ PET methodology is proving valuable in helping to assess the amyloid cascade hypothesis, as a diagnostic agent for brain amyloid deposition, and as a potential surrogate marker of therapeutic efficacy in anti-Aβ drug trials.