2-3-dihydro-1h-imidazo(1-2-b)pyrazole and pyridine

Non-invasive determination of amyloid-β peptide (Aβ) deposition has important significance for early diagnosis and medical intervention in Alzheimer's disease (AD). In this study, we investigated the availability of a radioiodinated imidazo[1,2-a]pyridine derivative, termed (125)I-DRK092, as single photon emission computed tomography (SPECT) ligand for in vivo detection of Aβ deposition. DRK092 showed high binding affinity for either synthetic human Aβ fibrils or brain homogenates from amyloid precursor protein transgenic (Tg) mouse (PS1-ki/JU-Tg2576) and AD patient with a dissociation constant (Kd) of one-digit nM, and excellent brain permeability (peak value of uptake: approximately 0.9% of injection dose/g rat brain). Ex vivo autoradiographic analysis showed that measurement with (125)I-DRK092 has higher sensibility for detecting Aβ accumulation than with (125)I-IMPY, a well-known amyloid SPECT ligand, in Tg mice. In vitro autoradiography with (125)I-DRK092 also confirmed higher accumulation of radioactivity in the cortical area, enriched with Aβ plaques, of Tg mouse and AD patient brains, as compared with the corresponding areas in non-Tg mouse and healthy control brains. All the data presented above lead us to draw the conclusion that radioiodinated DRK092 is a potential SPECT ligand for amyloid imaging in AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Autoradiography; Brain; Disease Models, Animal; Humans; Imidazoles; Iodine Radioisotopes; Mice; Plaque, Amyloid; Pyrazoles; Pyridines; Rats; Tomography, Emission-Computed, Single-Photon