Novel β‑amyloid PET Imaging Study of [18F]92 in Patients with Cognitive Decline

• Published in: ACS omega Vol. 9; no. 32; pp. 34675 - 34683
• Main Authors: Ni, Ming, Zhu, Xingxing, Wang, Kaixuan, Guo, Wenliang, Shi, Qin, Li, Yuying, Cui, Mengchao, Xie, Qiang
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 13.08.2024
• ISSN: 2470-1343; 2470-1343
• DOI: 10.1021/acsomega.4c03412

[18F]-4-((E)-(((E)-4-(2-(2-(2-Fluoroethoxy)­ethoxy)­ethoxy)­benzylidene)-hydrazono)­methyl)-N-methylaniline ([18F]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 [18F]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 [18F]92 was performed on the AllinOne module. Thirty one participants were recruited for this study. Dynamic [18F]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 [18F]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 Aβ42, Aβ40, P-tau181, and T-tau. The automated radiosynthesis of [18F]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 [18F]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, Aβ42 and the Aβ42/Aβ40 ratio exhibited negative correlations with global SUVR, while plasma P-tau181 and the P-tau181/T-tau ratio displayed positive correlations with global SUVR. [18F]92 exhibits excellent pharmacokinetic properties in the human brain and can be synthesized automatically on a large scale. [18F]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.