Novel β-amyloid PET Imaging Study of [ 18 F]92 in Patients with Cognitive Decline.
Ming NiXingxing ZhuKaixuan WangWenliang GuoQin ShiYuying LiMeng-Chao CuiQiang XiePublished in: ACS omega (2024)
[ 18 F]-4-(( E )-((( E )-4-(2-(2-(2-Fluoroethoxy)ethoxy)ethoxy)benzylidene)-hydrazono)methyl)- N -methylaniline ([ 18 F] 92 ) is a novel positron emission tomography (PET) tracer previously reported to exhibit high binding affinity to aggregated β-amyloid (Aβ). This study aims to report a fully automated radiosynthesis procedure for [ 18 F] 92 , explore its radioactive distribution in the brains of healthy subjects, and investigate its potential application value in the early diagnosis of Alzheimer's disease (AD). The fully automated radiosynthesis of [ 18 F] 92 was performed on the AllinOne module. Thirty one participants were recruited for this study. Dynamic [ 18 F] 92 PET imaging was conducted over 0-90 min period to assess time-activity curves (TAC) and standardized uptake value ratio (SUVR) curves in cognitively normal (CN) subjects. All participants were visually classified as either positive (+) or negative (-). Semiquantitative analyses of [ 18 F] 92 were performed by calculating SUVRs in different regions of interest. Furthermore, the study analyzed the relationships between global SUVR and plasma AD biomarkers, including Aβ 42 , Aβ 40 , P-tau181, and T-tau. The automated radiosynthesis of [ 18 F] 92 was completed within 50 min, yielding a radiochemical purity of greater than 95% and a radiochemical yield of 36 ± 3% (nondecay-corrected). Among the participants, 15 were estimated as Aβ (-) and 16 as Aβ (+). TACs indicated that [ 18 F] 92 rapidly crossed the blood-brain barrier within 10 min, followed by a rapid decrease, which then slowed down in the last 50-90 min. SUVR curves revealed that SUVR values stabilized around 60-70 min after injection and reached an equilibrium between 70 and 90 min, primarily in the cerebral cortex. SUVRs of Aβ (+) participants were significantly higher than those of Aβ (-) individuals within the cerebral cortex. In addition, Aβ 42 and the Aβ 42 /Aβ 40 ratio exhibited negative correlations with global SUVR, while plasma P-tau181 and the P-tau181/T-tau ratio displayed positive correlations with global SUVR. [ 18 F] 92 exhibits excellent pharmacokinetic properties in the human brain and can be synthesized automatically on a large scale. [ 18 F] 92 is a promising and reliable radiotracer for estimating Aβ pathology accumulation, providing valuable assistance in AD diagnosis and guiding clinical trials of therapeutic drugs.
Keyphrases
- pet imaging
- positron emission tomography
- cognitive decline
- computed tomography
- clinical trial
- machine learning
- squamous cell carcinoma
- high throughput
- cerebrospinal fluid
- randomized controlled trial
- deep learning
- transcription factor
- subarachnoid hemorrhage
- pet ct
- blood brain barrier
- study protocol
- single cell
- drug induced
- minimally invasive