Researchers are reporting positive results with two new PET tracers being developed to help diagnose Alzheimer's disease. The tracers, flutemetamol and florbetapir, may enable earlier diagnosis of Alzheimer's by identifying beta-amyloid plaque in brain tissue, according to two studies published July 11 in Archives of Neurology.
The results suggest that flutemetamol and florbetapir could play an increasingly prominent role in diagnosing forms of cognitive impairment in older adults. The critical element in both papers is the ability of the new PET tracers to identify beta-amyloid plaques, which have been associated with the potential to develop Alzheimer's disease.
Currently, beta amyloid is identified from brain samples taken during an autopsy to determine whether a person had Alzheimer's or some form of dementia. Should further studies pan out, the PET tracers could give clinicians new tools for the early detection of Alzheimer's.
PET and flutemetamol
In the first study, a research team led by Dr. David Wolk from the Penn Memory Center in Philadelphia evaluated the use of F-18 flutemetamol for imaging the brain. The PET agent from GE Healthcare is in phase III development to identify the uptake of beta amyloid by imaging brain tissue in live humans.
Wolk and colleagues performed 30-minute whole-body PET scans (Allegro, Philips Healthcare) on seven patients approximately 90 minutes after the administration of F-18 flutemetamol. PET imaging took place approximately three to 45 months after biopsy.
The researchers also analyzed a piece of cortical tissue approximately 0.5 cm in size, which was biopsied to determine normal pressure hydrocephalus, a progressive condition that includes dementia and can be difficult to distinguish from Alzheimer's disease.
The tissue was taken at the site of shunt entry in the right prefrontal cortex, which plays an important role in memory, attention, thought, and language. All biopsy sections were visually inspected for the presence or absence of beta-amyloid plaques.
The three readers evaluating the results found high concordance for their visual interpretations of the images, with disagreement on only one scan, which was rated as abnormal by two of the three readers. In four of seven scans, the biopsy tissue contained amyloid plaque pathology, according to Wolk and colleagues. The three normal F-18 flutemetamol scans were all in patients with no evidence of beta-amyloid plaque pathology.
The study showed "complete agreement" between visual reads of F-18 flutemetamol PET scans and histology, as well as a "significant relationship" between F-18 flutemetamol uptake and evidence of amyloid lesions, as seen in the biopsied tissue, the researchers concluded.
"To our knowledge, the present data represent the first study to compare the novel in vivo amyloid imaging ligand F-18 flutemetamol with in vivo histopathological evidence of [Alzheimer's disease]-related amyloid pathology," Wolk and colleagues wrote.
PET and florbetapir
The second study, led by Dr. Adam Fleisher from the Banner Alzheimer's Institute in Phoenix, evaluated PET imaging with the tracer F-18 florbetapir (Amyvid, Avid Radiopharmaceuticals) for detecting beta-amyloid plaque deposits.
Researchers enrolled 68 individuals with probable Alzheimer's disease, 60 participants with mild cognitive impairment, and 82 healthy individuals, all of whom were at least 55 years of age.
After calculating cerebral-to-whole-cerebellar florbetapir standardized uptake value ratios (SUVRs) and mean cortical SUVRs, Fleisher and colleagues determined that an SUVR threshold of 1.17 or greater would reflect pathological levels of amyloid associated with Alzheimer's disease, based on separate PET images taken before and after the death of 19 patients.
In addition, they used a threshold of SUVRs greater than 1.08 to determine the presence of identifiable beta amyloid. The number was chosen because it was the upper limit from a separate set of 46 individuals, ages 18 to 40 years, who did not carry the apolipoprotein E (APOE) gene variant. APOE affects function long before a person's brain begins to accumulate the beta amyloid that will eventually lead to dementia.
The results showed a significant difference among the three patient groups in mean cortical florbetapir SUVRs, with higher levels for individuals with increased pathology: 1.39 for the Alzheimer's group, 1.17 for those with mild cognitive impairment, and 1.05 for the healthy controls.
Regarding the percentage of patients who had SUVR levels associated with intermediate or high likelihood of Alzheimer's disease, the data also showed a significant difference between the groups: 81% for the Alzheimer's patients, 40% for those with mild cognitive impairment, and 21% for the control group.
Finally, in evaluating patients who met the SUVR criteria for the presence of any identifiable beta-amyloid plaque, 85% of the Alzheimer's patients met the criteria, compared with 47% of the mild cognitive impairment group and 28% of the healthy control subjects.
The findings "confirm the ability of florbetapir-PET SUVRs to characterize amyloid levels in clinically probable" Alzheimer's disease, mild cognitive impairment, and older healthy control groups, Fleisher and colleagues concluded.
"It introduces criteria to determine whether an image is associated with an intermediate-to-high likelihood of pathologic [Alzheimer's disease] or with having any identifiable cortical amyloid level above that seen in low-risk young controls," they wrote.
| Wolk's study was sponsored by GE Healthcare. Fleisher's study was funded by Avid Radiopharmaceuticals, a subsidiary of Eli Lilly. |
