Novel Dual-Functional Half-Curcumin Analogues as a Fluorescent and PET Probe for β-Amyloid Imaging in the Alzheimer's Disease APP/PS1 Model.

Noninvasive imaging of β-amyloid in vivo is pivotal for the early diagnosis of Alzheimer's disease (AD). While single imaging methods have been extensively studied for detecting Aβ over the past decade, dual-modal probes have received scant attention. In this study, we synthesized and assessed a series of half-curcumin probes, among which DiFboron-8 demonstrated a high affinity and selectivity for Aβ aggregates. DiFboron-8 effectively served as a dual-functional fluorescent and positron emission tomography (PET) probe for imaging β-amyloid in an AD mouse model. Histological staining results underscored DiFboron-8's potent staining capability for Aβ plaques in APP/PS1 brain slices, while ex vivo biodistribution studies highlighted its rapid clearance rate. In vivo imaging revealed that [18F]-DiFboron-8 could penetrate the blood-brain barrier, displaying higher PET signals in the brains of APP/PS1 mice compared to wild-type mice just 3 min postinjection, a finding corroborated by autoradiography staining. Overall, we propose that [18F]-DiFboron-8 represents an efficient fluorescent/PET dual-modal probe, offering promise for β-amyloid imaging in the early stages of AD.