PET imaging utility of a novel Aβ-tracking PET radiotracer, [18F]FC119S in aged vervet monkeys

BACKGROUND: Alzheimer’s disease is characterized by the deposition of amyloid-beta (Aβ) plaques, necessitating early detection and reliable biomarkers for effective intervention. Non-human primates, particularly aged vervet monkeys, offer valuable models for studying age-related Aβ pathology due to their close phylogenetic relationship to humans and similar neuropathological features. METHODS: This study assessed the utility of [18F]FC119S, a novel Aβ-targeting PET radiotracer, in aged vervet monkeys. The radiochemistry of [18F]FC119S was optimized and automated to ensure high radiochemical purity and molar activity. PET/MRI imaging was performed to evaluate tracer uptake, distribution, and washout kinetics. Correlations between [18F]FC119S uptake and cerebrospinal fluid (CSF) and plasma biomarkers—including Aβ42/40 ratio, pTau181, neurofilament light chain (NfL), and pTau181/Aβ42 ratio—were analyzed. Autoradiography was conducted to validate regional tracer binding in brain tissues. RESULTS: [18F]FC119S demonstrated high brain uptake, rapid washout, and widespread cortical distribution in vervet monkeys, mirroring patterns observed in human studies. Tracer uptake showed negative associations with CSF Aβ42/40 ratio in Aβ-affected regions, and significant positive correlations with CSF pTau181 and CSF pTau181/Aβ42 ratio in the temporal lobe. Additionally, significant positive correlations were observed between [18F]FC119S uptake and CSF NfL in the anterior cingulate gyrus, parietal, and occipital lobes. Autoradiography confirmed elevated tracer binding in specific brain regions of older vervets with low CSF Aβ42 compared to younger counterparts. CONCLUSIONS: These findings validate [18F]FC119S as a promising PET radiotracer for tracking Aβ deposition in aged vervet monkeys. Its imaging characteristics and biomarker correlations support its translational potential for Alzheimer’s disease research and early diagnostic applications.