PET Scan for brain amyloid is strong predictor of aMCI

New study data presented at the Alzheimer's Association International Conference 2014 showed that a positive [18F]flutemetamol PET scan for brain amyloid was a highly significant predictor of progression from amnestic Mild Cognitive Impairment (aMCI) to probable Alzheimer's disease (pAD). A second study further demonstrated the diagnostic value of [18F]Flutemetamol in confirming the presence of neuritic amyloid in those patients with early onset dementia. Flutemetamol is GE Healthcare's investigational radiopharmaceutical product for PET imaging of beta amyloid neuritic plaque density in the brains of adult patients with cognitive impairment who are being evaluated for Alzheimer's disease and other causes of cognitive impairment.

"Collectively, these data demonstrate the diagnostic value of [18F]flutemetamol and add to the growing body of evidence that it can help physicians identify the histopathology associated with an Alzheimer's disease diagnosis in specific patients," said Ger Brophy, CTO, Life Sciences, GE Healthcare. "If and when approved in the European Union, [18F]flutemetamol will be an important tool to support assessments of patients with cognitive disorders, as well as being a valuable research tool in the hunt for therapies to combat Alzheimer's."

In the study, 232 participants with MCI, a diagnosis characterized by cognitive deficits not severe enough to impact daily functioning and thus not meeting the definition of dementia, received a [18F]flutemetamol injection and underwent brain scans. The study showed those with positive VIZAMYL scans were about 2.5 times more likely to convert to pAD than those with negative scans. The ability of positive [18F]flutemetamol PET images to identify aMCI patients at higher risk of progressing to AD could potentially allow for better patient evaluation and management, and support patient stratification in enrolment into clinical trials for disease modifying drugs

"These findings demonstrate the potential role of [18F]flutemetamol in stratifying those patients at higher risk of developing Alzheimer's disease, beyond its use as a diagnostic tool," said David Wolk, assistant director, Penn Memory Center (Philadelphia) and lead investigator of the study. "In addition to providing patients with potentially important prognostic information about their likelihood of developing dementia, identifying high risk patients could help guide physicians' recommendations for patient monitoring, care plans and use diagnostic resources. These are exciting results, but we need further research to fully understand how this might be used in clinical practice."

In the second study, 80 patients with early onset dementia (younger than age 70), and with physician diagnostic confidence less than 90% , underwent [18F]flutemetamol PET scans which were assessed as either amyloid positive or negative. Clinical diagnosis and diagnostic confidence was determined, both before and after disclosure of the scan results. This study demonstrated that the use of [18F]flutemetamol increased diagnostic confidence for physicians, and in many patients, helped to confirm or exclude the diagnosis of Alzheimer's disease and lead to changes in management.

"Early and accurate diagnoses may have implications for both prognosis and treatment among patients with early onset dementia," said Marissa Zwan, VU University Medical Center (Amsterdam) and lead investigator of the study. "Greater diagnostic confidence supports better patient management and helps physicians to determine appropriate treatment options, as well as helping patients and caregivers to plan for the future."

The data showed that 20% of patients had a change in diagnosis following review of the [18F]flutemetamol scan. In particular, for those patients diagnosed with Alzheimer's disease prior to a [18F]flutemetamol scan and who had an amyloid negative result, clinical diagnosis changed in 12 of 15 patients. Overall, confidence in diagnosis significantly increased from 67(±12)% to 90(±16) percent after disclosing PET results. Additionally, in 48% of patients, 18F]flutemetamol PET results led to a change in patient healthcare management (i.e. medication changes, additional care).

Beta-Amyloid imaging gives new

insight on Alzheimer's disease

Eli Lilly and Company (Indianapolis) reported new data showing that beta-amyloid imaging was associated with altered diagnosis and management of patients with Alzheimer's disease. Change in management was observed in both patients who met and did not meet the Appropriate Use Criteria (AUC), which were developed by the Society of Nuclear Medicine and Molecular Imaging (Reston, Virginia) and the Alzheimer's Association (Minneapolis) to provide guidance on which patients are most appropriate for imaging and how best to use the results. These data were presented today at the Alzheimer's Association International Conference 2014 (AAIC 2014) in Copenhagen, Denmark by Andrew Siderowf, medical director, Avid Radiopharmaceuticals (Philadelphia), a wholly owned subsidiary of Lilly. The data were also featured by the AAIC in a research media tips sheet.

"This study included patients in which there was diagnostic uncertainty by the treating physician and found that changes in diagnosis and management of Alzheimer's disease did not vary between patients depending on whether they met the Appropriate Use Criteria or not. In addition, analysis of beta-amyloid scans conducted post-diagnosis indicated that many patients being treated with medications may have potentially been misdiagnosed and inappropriately treated," said Siderowf. "While we support the development of the Appropriate Use Criteria, one of the clearest insights resulting from these data is that we need to continue to fine tune our understanding of the appropriate use of these tools and their utility for patients facing a diagnosis of Alzheimer's disease."

The objective of the study was to evaluate which patients are most likely to receive different care if they had an amyloid PET scan as part of their diagnostic work-up. In particular, the study evaluated if patients who met the working definition of the AUC would be more affected than those who did not. The AUC guidelines propose that patients who are being evaluated for dementia with atypical presentations, younger patients, and patients with unexplained mild cognitive impairment, are most appropriate for amyloid PET imaging. For the patient to be included in the study, Alzheimer's disease had to be under consideration and the treating physician had to have uncertainty regarding the diagnosis.

Results showed that 59% of subjects met the working definition of AUC. Forty-seven percent of the AUC-like cases were amyloid positive compared to 62% of non-AUC cases. Diagnosis changed after PET scan for 58% of AUC cases versus 45% of non-AUC cases (p=0.10). The proportion of patients with change in management plan was high for both AUC (88%) and non-AUC (77 percent) cases. In particular, the use of Alzheimer's disease medications including cholinesterase inhibitors, or memantine, declined after a negative florbetapir F 18 scan by 20% (from 26/54 to 15/54 cases; p=0.002) in AUC cases and by 33% (from 17/27 to 8/27 cases; p=0.004) in non-AUC cases. Diagnoses for non-AUC cases in which Alzheimer's disease medications were withdrawn after a negative scan included prodromal Alzheimer's disease/mild cognitive impairment due to Alzheimer's disease (n=8), or mild cognitive impairment of uncertain etiology (n=1). This study found that patients with an uncertain diagnosis, but who are not otherwise explicitly captured by AUC, may be reasonable candidates for amyloid imaging.

Nano particle aids in early cancer detection

Scientists have designed a new self-assembling nanoparticle that targets tumors, to help doctors diagnose cancer earlier. The new nanoparticle, developed by researchers at Imperial College London, boosts the effectiveness of MRI scanning by specifically seeking out receptors that are found in cancerous cells. The nanoparticle is coated with a special protein, which looks for specific signals given off by tumors, and when it finds a tumor it begins to interact with the cancerous cells. This interaction strips off the protein coating, causing the nanoparticle to self-assemble into a much larger particle so that it is more visible on the scan.

A new study published in the journal Angewandte Chemie, used cancer cells and mouse models to compare the effects of the self-assembling nanoparticle in MRI scanning against commonly used imaging agents and found that the nanoparticle produced a more powerful signal and created a clearer MRI image of the tumor. The scientists say the nanoparticle increases the sensitivity of MRI scanning and will ultimately improve doctor's ability to detect cancerous cells at much earlier stages of development.

Nicholas Long from the department of chemistry at Imperial College London said the results show real promise for improving cancer diagnosis. "By improving the sensitivity of an MRI examination, our aim is to help doctors spot something that might be cancerous much more quickly. This would enable patients to receive effective treatment sooner, which would hopefully improve survival rates from cancer."

"MRI scanners are found in nearly every hospital up and down the country and they are vital machines used every day to scan patients' bodies and get to the bottom of what might be wrong. But we are aware that some doctors feel that even though MRI scanners are effective at spotting large tumors, they are perhaps not as good at detecting smaller tumors in the early stages," added Long.

The newly designed nanoparticle provides a tool to improve the sensitivity of MRI scanning, and the scientists are now working to enhance its effectiveness. Long said, "We would like to improve the design to make it even easier for doctors to spot a tumor and for surgeons to then operate on it. We're now trying to add an extra optical signal so that the nanoparticle would light up with a luminescent probe once it had found its target, so combined with the better MRI signal it will make it even easier to identify tumors."

Before testing and injecting the non-toxic nanoparticle into mice, the scientists had to make sure that it would not become so big when it self-assembled that it would cause damage. They injected the nanoparticle into a saline solution inside a petri dish and monitored its growth over a four hour period. The nanoparticle grew from 100 to 800 nanometers – still small enough to not cause any harm.

The scientists are now improving the nanoparticle and hope to test their design in a human trial within the next three to five years. Juan Gallo from the department of surgery and cancer at Imperial College London said, "We're now looking at fine tuning the size of the final nanoparticle so that it is even smaller but still gives an enhanced MRI image. If it is too small the body will just secrete it out before imaging, but too big and it could be harmful to the body. Getting it just right is really important before moving to a human trial."

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