Abstract
616
Objectives: t is known that, after ischemic stroke, neuroinflammatory processes occur which represent interesting treatment targets. However, sufficient in vivo imaging of these processes, particularly in acute and subacute stages, was not possible upon till now. During neuroinflammation, alpha7-nicotinic acetylcholine receptors (nAChRs) are overexpressed. We, thus, tested the novel alpha7-nAChR ligand [18F]DBT10 for its potential to image post-stroke neuroinflammation. In 10 adult Merino sheep, the left middle cerebral artery was permanently occluded (pMCAO, day 1). On day 0 (baseline) as well as 4hrs after pMCAO, and on days 7 and 14, simultaneous dynamic (120min) brain PET/MRI (Siemens Biograph mMR, ~300MBq [18F]DBT10, arterial blood sampling, metabolite HPLC) was conducted. Parallel [15O]H2O PET and standard stroke MRI sequences were employed to segment the stroke compartments. Directly after PET/MRI on day 14, the brains were objected to ex vivo autoradiography (AR) and histopathology. In addition to the stroke sheep, control sheep (n=3, no or sham surgery) were investigated. [18F]DBT10 was metabolized with a half-life of 18min in blood. It showed a fast washout from cerebellum and reached a plateau in cortical brain areas at 60min p.i. The control sheep as well as the sheep on day 0 did not show any imaging abnormalities. In the sheep after pMCAO, the [18F]DBT10 PET image uptake was reduced in the stroke areas on day 1 (SUVRs110-120min p.i.=0.94±0.04) and day 7 (0.90±0.17), and intensively increased in the infarction border on day 14 (1.82±0.72; p<0.01). The PET results on day 14 were confirmed by AR and correlated histopathologically with microglia activation and macrophage infiltration. We conclude that [18F]DBT10 is promising for PET imaging of neuroinflammation occurring after ischemic stroke. Further investigations to model the tracer kinetics and to clarify the role of alpha7-nAChRs in this regard are ongoing.