Characterisation of radioiodinated flavonoid derivatives for SPECT imaging of cerebralprion deposits

摘要

Prion diseases are fatal neurodegenerative diseases characterised by deposition of amyloid plaques containing abnormal prion protein aggregates (PrP^Sc). This study aimed to evaluate the potential of radioiodinated flavonoid derivatives for single photon emission computed tomography (SPECT) imaging of PrP^Sc. In vitro binding assays using recombinant mouse PrP (rMoPrP) aggregates revealed that the 4-dimethylamino-substituted styrylchromone derivative (SC-NMe2) had higher in vitro binding affinity (Kd = 24.5 nM) and capacity (Bmax = 36.3 pmolmol protein) than three other flavonoid derivatives (flavone, chalcone, and aurone). Fluorescent imaging using brain sections from mouse-adapted bovine spongiform encephalopathy (mBSE)-infected mice demonstrated that SC-NMe2 clearly labelled PrP^Sc-positive prion deposits in the mice brain. Two methoxy SC derivatives, SC-OMe and SC-(OMe)2, also showed high binding affinity for rMoPrP aggregates with Ki values of 20.8 and 26.6 nM, respectively. In vitro fluorescence and autoradiographyexperiments demonstrated high accumulation of [¹²⁵I]SC-OMe and[¹²⁵I]SC-(OMe)2 in prion deposit-rich regions of themBSE-infected mouse brain. SPECT/computed tomography (CT) imaging and ex vivoautoradiography demonstrated that [¹²³I]SC-OMe showed consistentbrain distribution with the presence of PrP^Sc deposits in themBSE-infected mice brain. In conclusion, [¹²³I]SC-OMe appears apromising SPECT radioligand for monitoring prion deposit levels in the livingbrain.