The effect of pharmacological inhibition of Serine Proteases on neuronal networks .

Neurons are embedded in an extracellular matrix (ECM), which functions both as a scaffold and as a regulator of neuronal function. The ECM is in turn dynamically altered through the action of serine proteases, which break down its constituents. This pathway has been implicated in the regulation of synaptic plasticity and of neuronal intrinsic excitability.

Decreased levels of active uPA and KLK8 assessed by [ In]MICA-401 binding correlate with the seizure burden in an animal model of temporal lobe epilepsy.

Objective: Urokinase-type plasminogen activator (uPA) and kallikrein-related peptidase 8 (KLK8) are serine proteases that contribute to extracellular matrix (ECM) remodeling after brain injury. They can be labelled with the novel radiotracer [ In]MICA-401. As the first step in exploring the applicability of [ In]MICA-401 in tracing the mechanisms of postinjury ECM reorganization in vivo, we performed in vitro and ex vivo studies, assessing [ In]MICA-401 distribution in the brain in two animal models: kainic acid-induced status epilepticus (KASE) and controlled cortical impact (CCI)-induced traumatic brain injury (TBI).

Preclinical evaluation of [ In]MICA-401, an activity-based probe for SPECT imaging of in vivo uPA activity.

Urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 are key players in cancer invasion and metastasis. Both uPA and PAI-1 have been described as prognostic biomarkers; however, non-invasive methods measuring uPA activity are lacking. We developed an indium-111 ( In)-labelled activity-based probe to image uPA activity in vivo by single photon emission computed tomography (SPECT).