Target-Specific PET Probes for Neurodegenerative Disorders Related to Dementia

Abstract

Dementia is a highly prevalent problem causing considerable disability and mortality and exacting great costs to individuals, their families, and society. The 4 most common neurodegenerative disorders that cause dementia-Alzheimer disease, frontotemporal dementia, dementia with Lewy bodies, and dementia in Parkinson disease-have different underlying etiologies and pathogenetic mechanisms. There is a great need for early diagnostic markers; functional brain imaging may therefore assist in the detection and differential diagnosis of dementia due to neurodegenerative diseases. Functional imaging such as PET allows in vivo imaging of functional brain activity indicating cerebral blood flow and cerebral glucose metabolism, and PET allows imaging of neurotransmitter activity, including that of the cholinergic, dopaminergic, and serotonergic systems. New PET neuroimaging tracers are being developed for detecting pathologic parameters such as amyloid plaque and microglial activity. The development of molecular imaging is important for early diagnosis of dementia, selection of patients for therapies, and evaluation of therapies.

Diagnosis of Dementia Using Nuclear Medicine Imaging Modalities

“…In addition, microglial activation is also thought to play a significant role in the immune response to AD-related neuronal degeneration and, in AD patients, activated microglia can be found at sites associated with the deposition of aggregated Aβ (Kadir and Nordberg, 2010). There is consequently significant interest in developing radiopharmaceuticals that allow exploration of microglial activation using PET imaging, and the most common are ligands that target the peripheral benzodiazepine receptor including [ 11 C]PK11195 and [ 11 C]PBR28.…”

“…Cagnin, et al, 2004). Alternatively, an amyloid positive scan would strongly suggest AD, whilst an amyloid negative scan would indicate FTD ( Figure 5) (Kadir and Nordberg, 2010). J Nucl Med.…”

Biomarkers for the early diagnosis of Alzheimer’s disease: The challenge of XXI century

“…Several neurotransmission, especially the cholinergic system but also the dopaminergic and serotonergic, is 13 [42] have been employed to measure acetylcholinesterase activity and a reduction was found in AD patients, respect to healthy controls. Reduction in acetylcholinesterase activity has also been reported in MCI patients who later convert to AD, suggesting that acetylcholinesterase changes might precede the development of clinical AD.…”

Molecular imaging markers in clinical trials in Alzheimer's disease

“…In addition to amyloid ligands in various PET tracers are available for measurement of neurotransmitter functions inlcluding, enzyme activities and receptor densities. Furthermore in addition different PET ligands are under development for studies of pathological processes characteristic for AD such as neurofibrillary tangles as well as inflammatory processes as microglia and astrocytes (3). The new molecular imaging markers may thus provide a deeper insight into ongoing disease processes of AD as well as further understanding of drug mechanisms compared with solely measuring functional changes as cerebral blood flow, cerebral glucose metabolisms or cognitive performances.…”