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The development of a novel 18F-labeled PET amyloid imaging agent, 18F-AV-45, may eventually provide a practical approach for routine brain imaging for Alzheimer's, researchers say.

A major recent advance in Alzheimer's is the ability to create images of amyloid in the brains of living people using positron emission tomography (PET) scanners. With PET, a radioactive compound, or tracer, is injected into the person to be scanned. The tracer attaches to a target substance in the body, in this case amyloid, which then "lights up" on the image captured by the scanner.

In research reported at ICAD 2008, Michael J. Pontecorvo, PhD, of Avid Radiopharmaceuticals, Philadelphia, PA, and colleagues reported the development of a novel 18F-labeled PET amyloid imaging agent, 18F-AV-45, that may eventually provide a practical approach for routine brain imaging for Alzheimer's.

PET scanners are relatively common - they are available in most hospitals - yet one of the challenges to more widespread use of PET imaging in Alzheimer's is that the radioactivity of the first amyloid-imaging tracer, called 11C-PIB or Pittsburgh Compound B, is relatively short-lived. With this agent, based on radioactive carbon, half of the radioactivity is lost every 20 minutes. This means that it must be manufactured onsite, a process that requires a cyclotron (a type of particle accelerator), which is rarely found in community hospitals. This limitation has prompted a search for longer-lived tracers, such as 18F-labeled agents, based on radioactive fluorine, which would be suitable for regional production and wider community use.

In the study, three 18F-labeled compounds were evaluated in 42 cognitively healthy elderly volunteers and 39 individuals with Alzheimer's. Each participant received a single intravenous injection of one of the compounds followed by PET imaging.

People with Alzheimer's showed retention of all three tracers in brain areas expected to be high in amyloid. In contrast, cognitively healthy volunteers showed rapid removal of the tracers, with minimal retention in the brain. Two individuals diagnosed with Alzheimer's had a pattern of tracer uptake similar to healthy volunteers. Chart notes for both suggested unusual presentations - prominent Parkinsonism in one case and slowly progressive dementia in the other.

While the three compounds were similar in pattern and amount of tracer retention, they differed in how they were processed by the body in ways that favored one compound, 18F-AV-45. For example, 18F-AV-45 showed rapid uptake and steady levels were maintained in the brain between 50 and 90 minutes post injection. This allowed high quality images to be obtained from PET imaging beginning 50 minutes after 18F-AV-45 administration, with minimal inconvenience or delay for the patient or the imaging center, according to the researchers.

"18F-AV-45 is being used as a research tool today, but it has the potential to aid in the diagnosis and early detection of Alzheimer's in a community setting and may be a useful biomarker for the development and monitoring of novel amyloid reducing therapies," Pontecorvo said. "On the basis of the findings we reported today, Phase II trials with 18F-AV-45 have been initiated."