Multi-fluorine labeled indanone derivatives as potential MRI imaging probes for β-Amyloid plaques.

In order to realize the early diagnosis of Alzheimer's disease (AD), we designed and synthesized a series of multi-fluorine labeled indanone derivatives based on indanone which could target β-amyloid (Aβ). Through the in vitro staining experiment and affinity experiment, we selected 7d out, and then evaluated it through other in vivo and in vitro experiments. The staining of AD human brain adjacent sections revealed that compound 7d could bind to Aβ plaques with high affinity. In the in vitro binding assay, 7d showed a balanced affinity with Aβ1-40 (Kd = 367 ± 13) and Aβ1-42 (Kd = 384 ± 56). Also, 7d exhibited a low toxicity (LD50 > 50 mg/kg) and an excellent ability to pass through the blood-brain barrier (Log p = 3.87). The biodistribution experiment in mice showed that 7d reached the highest brain uptake after 1 h of tail vein injection and cleared after 24 h. A low concentration of 7d (1.875 mg/ml) showed a strong imaging ability (19F-weighted mode), and the imaging capability increased with the increasing of concentration. All the results showed that 7d could provide a feasible solution for the early diagnosis of AD under non-radioactive condition.