PET scanning is a powerful imaging technique that enables in vivo examination of brain functions. It allows for noninvasive quantification of cerebral blood flow, metabolism, and receptor binding. PET scanning helps in understanding the disease’s pathogenesis, making the correct diagnosis, and monitoring the disease’s progression and response to treatment.[35]
PET scanning involves the introduction of a radioactive tracer into the human body, usually with an intravenous injection. A tracer is essentially a biologic compound of interest that is labeled with a positron-emitting isotope, such as carbon-11 (11 C), fluorine-18 (18 F), or oxygen-15 (15 O). These isotopes are used because they have relatively short half-lives (from minutes to < 2h), allowing the tracers to reach equilibrium in the body without exposing the subjects to prolonged radiation.
The 2 most common physiologic process measurements performed using PET scanning are glucose with [18 F]FDG and cerebral blood flow using water.[23]
FDG-PET has been used extensively to study Alzheimer disease, and it is evolving into an effective tool for early diagnosis and for differentiation of Alzheimer disease from other types of dementia. FDG-PET has been used to detect persons at risk for Alzheimer disease even before the onset of symptoms.[36]
Patients with Alzheimer disease have characteristic temporoparietal glucose hypometabolism, the degree of which is correlated with the severity of dementia.[37] (Temporal and parietal glucose hypometabolism is widely seen on PET images in patients with Alzheimer disease.) With disease progression, frontal involvement may be evident. Glucose hypometabolism in Alzheimer disease is likely to be caused by a combination of neuronal cell loss and decreased synaptic activity.[38]
In control subjects, entorhinal cortex hypometabolism on FDG-PET has predictive value in the progression of dementia to MCI or, even, to Alzheimer disease.[39, 40] The identification of asymptomatic individuals at risk will have an enormous role in the treatment strategy for Alzheimer disease.[41] Individuals at high risk for Alzheimer disease (asymptomatic carriers of the APOE*E4 allele) exhibit a pattern of glucose hypometabolism similar to that of patients with Alzheimer disease. After a mean follow-up of 2 years, the cortical metabolic abnormality continues to decline despite preservation of cognitive performance.[42, 40]
In patients with Alzheimer disease, PET performed with ligand PK11195 labeled with11 C, or (R)-[11 C] PK11195, showed increased binding in the entorhinal, temporoparietal, and cingulate cortices. This finding corresponded to the postmortem distribution of Alzheimer disease pathology.[43]
Degree of confidence
Despite the technical differences, results from PET and SPECT scanning are comparable, although data suggest that PET scanning is more sensitive than SPECT scanning.[44] On PET or SPECT scanning, mild Alzheimer disease may be more difficult to detect than moderate or severe disease. In Alzheimer disease, FDG-PET has a sensitivity of 94% and a specificity of 73%. It can also be used to correctly predict a progressive course of dementia with a 91% sensitivity and a nonprogressive course with a 75% specificity.[45] Efforts to develop a specific ligand for Aß plaques may further enhance the sensitivity of PET scanning for early diagnosis of Alzheimer disease and may provide a biologic marker of disease progression.[43]
In their study, Boxer et al reported that different amyloid-binding PET scan agents—Pittsburgh Compound-B and FDDNP—may have differential sensitivity to prion-related brain pathology and that a combination of amyloid imaging agents may be useful in the diagnosis of early onset dementia.[46]
Florbetapir F 18 (AMYViD) was approved by the FDA in April 2012 as a diagnostic imaging agent. It is indicated for PET brain imaging of beta-amyloid neuritic plagues in adults being evaluated for Alzheimer disease or other cognitive decline.
Approval for florbetapir F 18 was based on 3 clinical studies that examined images from healthy adult patients as well as patients with a range of cognitive disorders, including some terminally ill patients who had agreed to participate in a postmortem brain donation program. Measurements from postmortem cortical amyloid burden correlated with median florbetapir F 18 scores (r=0.78; P< 0.0001).[47]
In a study by Clark et al, the presence and density of beta amyloid correlated closely in individuals who had florbetapir-PET imaging within 99 days before death and then upon autopsy.[48] Patients with probably Alzheimer disease, mild cognitive impairment, or older healthy controls showed significantly different mean cortical florbetapir uptake value ratios in a study by Fleisher et al.[49]