Whole-body biodistribution and brain PET imaging with [18F]AV-45, a novel amyloid imaging agent — a pilot study

PurposeThe compound (E)-4-(2-(6-(2-(2-(2-18F-fluoroethoxy)ethoxy)ethoxy) pyridin-3-yl)vinyl)-N-methylbenzenamine ([18F]AV-45) is a novel radiopharmaceutical capable of selectively binding to β-amyloid (Aβ) plaques. This pilot study reports the safety, biodistribution, and radiation dosimetry of [18F]AV-45 in human subjects.MethodsIn vitro autoradiography and fluorescent staining of postmortem brain tissue from patients with Alzheimer's disease (AD) and cognitively healthy subjects were performed to assess the specificity of the tracer. Biodistribution was assessed in three healthy elderly subjects (mean age: 60.0±5.2 years) who underwent 3-h whole-body positron emission tomography (PET)/computed tomographic (CT) scans after a bolus injection of 381.9±13.9 MBq of [18F]AV-45. Another six subjects (three AD patients and three healthy controls, mean age: 67.7±13.6 years) underwent brain PET studies. Source organs were delineated on PET/CT. All subjects underwent magnetic resonance imaging (MRI) for obtaining structural information.ResultsIn vitro autoradiography revealed exquisitely high specific binding of [18F]AV-45 to postmortem AD brain sections, but not to the control sections. There were no serious adverse events throughout the study period. The peak uptake of the tracer in the brain was 5.12±0.41% of the injected dose. The highest absorbed organ dose was to the gallbladder wall (184.7±78.6 μGy/MBq, 4.8 h voiding interval). The effective dose equivalent and effective dose values for [18F]AV-45 were 33.8±3.4 μSv/MBq and 19.3±1.3 μSv/MBq, respectively.Conclusion[18F]AV-45 binds specifically to Aβ in vitro, and is a safe PET tracer for studying Aβ distribution in human brain. The dosimetry is suitable for clinical and research application.