Amyloid imaging is now promising earlier Alzheimer’s disease diagnoses and potential anti-amyloid therapies in the not-too-distant future. The radiotracer C-11 Pittsburgh compound-B (C-11 PiB) has been proven effective for amyloid PET imaging and has outperformed many F-18 bound biomarkers, but the radiotracer F-18 NAV4694 is showing a binding pattern that nearly mirrors that of C-11 PiB with all the logistical perks of a fluorine-based agent, according to research being published in the June edition of The Journal of Nuclear Medicine.
Christopher C. Rowe, MD, a professor of nuclear medicine at Austin Health in Melbourne, Australia, and colleagues, conducted a head-to-head comparison of C-11 PiB and F-18 NAV4694 PET radiotracers to determine how they imaged amyloid plaque in the brain both visually and quantitatively.
A range of F-18 based amyloid imaging agents have been developed, including Florbetapir, as well as other phase III investigational agents florbetaben and flutemetamol, but C-11 PiB has typically shown stronger cortical binding than F-18 conjugated biomarkers, which also tend to bind to more non-specific white matter. Amyloid binding in white matter is not associated with Alzheimer’s pathology and can complicate visual interpretation. However, expansion of C-11 PiB is limited by production logistics. Due to its radioactive half-life of 20 minutes, C-11 PiB requires an on-site cyclotron, whereas F-18 radiotracers have a 110 minute half-life much more conducive for commercialization and distribution.
F-18 NAV4694, previously named AZD4694, has a chemical structure similar to C-11 PiB. This is the first study of its kind comparing the two biomarkers. Results of the study raised the bar for F-18 amyloid imaging tracers, with F-18 NAV4694 landing at the top of the heap for its almost duplicated uptake compared to C-11 PiB and relatively low binding to nonspecific white matter compared to other fluorine compounds.
“F-18 NAV4694 displays imaging characteristics nearly identical to those of C-11 PiB,” wrote Rowe et al. “The low white matter and high cortical binding in [Alzheimer’s patients] indicate that this tracer is well suited to both clinical and research use.”
A total of 45 subjects, all over the age of 60, including seven patients with suspected Alzheimer’s disease, three with likely frontotemporal dementia, 10 with mild cognitive impairment and 25 healthy controls, were recruited for this prospective study. All participants underwent separate PET C-11 PiB and F-18 NAV4694 neuroimaging studies. Scans were taken before the 70-minute mark after injection. Data included MRI coregistration of images, standardized uptake value ratios and matched region-of-interest in the same patients.
Alzheimer’s patients displayed higher beta-amyloid burden in both C-11 PiB and F-18 NAV4694 imaging studies, and significantly more so than for healthy controls, with cortical binding exceeding white matter binding throughout.
“The high cortical binding [for Alzheimer's patients] and low nonspecific white matter binding also suggests that F-18 AZD4694 images may be more easily and reliably read in clinical practice than other F-18 labeled PET tracers for brain amyloid,” the authors concluded.
Approximately 16 percent of healthy controls tested positive for amyloid burden using both biomarkers and researchers deemed this further proof that buildup of amyloid plaque is representative of early Alzheimer’s disease development prior to noticeable cognitive impairment.