SPECT Imaging Agents for Detecting Cerebral β-Amyloid Plaques

Masahiro Ono,Hideo Saji

doi:10.1155/2011/543267

Abstract

The development of radiotracers for use in vivo to image β-amyloid (Aβ) plaques in cases of Alzheimer's disease (AD) is an important, active area of research. The presence of Aβ aggregates in the brain is generally accepted as a hallmark of AD. Since the only definitive diagnosis of AD is by postmortem staining of affected brain tissue, the development of techniques which enable one to image Aβ plaques in vivo has been strongly desired. Furthermore, the quantitative evaluation of Aβ plaques in the brain could facilitate evaluation of the efficacy of antiamyloid therapies currently under development. This paper reviews the current situation in the development of agents for SPECT-based imaging of Aβ plaques in Alzheimer's brains.

Highlights

Alzheimer’s disease (AD) is an age-related, irreversible form of dementia characterized by memory loss, a progressive decline in intellectual ability, language impairment, and personality and behavioral changes that eventually interfere with daily life
The differential diagnosis for AD includes a large number of other diseases such as vascular dementia, frontal temporal lobe dementia (FTLD) complex, and dementia with Lewy bodies (DLB) as well as rarer neurodegenerative diseases such as Creutzfeld-Jacob disease (CJD)
Clinical trials in AD patients have been conducted with several positron emission computed tomography (PET) imaging agents including [11C]PIB [8,9,10], [11C]SB-13 [6, 11], [11C]BF-227 [12], [11C]AZD2184 [13], [18F]FDDNP [14,15,16], [18F]BAY94-9172 [7, 17, 18], [18F] AV-45 [19,20,21], and [18F]GE-067 [22] (Figure 2), indicating the imaging of Aβ plaques in living brain tissue to be useful for the diagnosis of AD

Summary

Introduction

Alzheimer’s disease (AD) is an age-related, irreversible form of dementia characterized by memory loss, a progressive decline in intellectual ability, language impairment, and personality and behavioral changes that eventually interfere with daily life. To facilitate the early diagnosis of this disease, there is an urgent need for the sensitive noninvasive detection of biomarkers for the pathophysiology Toward achieving this goal, nuclear imaging techniques such as positron emission computed tomography (PET) and single photon emission computed tomography (SPECT) have been employed. The basic requirements for suitable Aβ imaging agents include (i) good penetration of the bloodbrain barrier, (ii) selective binding to Aβ plaques, and (iii) clear and contrasting signals between plaques and nonplaques (Figure 1). Based on these requirements, several promising agents with the backbone structure of DDNP, thioflavin-T and Congo Red have been synthesized and evaluated for use in vivo as probes to image Aβ plaques in AD brain. We summarize the current situation in the development of probes for SPECT-based imaging of Aβ plaques in Alzheimer’s brains

Radioiodinated Probes for Imaging of Aβ Plaques

Findings

Conclusion