Arisla | The research

Active Project: PETALS II

PETALS II Positron Emission Tomography and Amyotrophic Lateral Sclerosis: study of Cannabinoid subtype 2 receptor expression in ALS experimental model

The main aim of PETALS II proposal is to explore the possibility of using selective radioligands of Cannabinoid subtype 2 Receptors (CB2R) and Positron Emission Tomography (PET), applied to small animal, as perspective in vivo imaging biomarker of Amiotrophycal Lateral Schlerosis (ALS). This hypothesis is based on the demonstration of the possibility to detect CB2R expression in vivo, linked to microglia activation/neuroinflammation, and correlate such an expression with symptom onset/progression in an animal model of ALS (transgenic mice SOD1-G93A). This target will be achieved by radiolabeling, using a positron-emitting nuclide (18F), 4 candidate molecules that proved to have a remarkable affinity for CB2R, high CB2R vs CB1R selectivity and lipophilicity in the optimal range for Blood Brain Barrier (BBB) crossing. Unlabeled molecules have been already synthesized, screened for pharmacology and used in scout labeling by partners of the consortium. The ligands will be radiolabeled, formulated for injection and administered in wild and SOD1 mice. In particular, SOD1 mice will be studied at different times before and after the onset of symptoms of motor neuron impairment. PET images will be analysed to highlight CNS uptake differences and peripheral organ distribution of the radioligands in wild and transgenic animals. After the PET scan, animals will be sacrificed and organ radioactivity distribution measured. CB2R expression on the excised tissues will be assessed by literature available methods (namely quantitative polymerase chain reaction and western immunoblotting). The project is organised in 4 Workpackages according to major tasks: Management/coordination/data pooling and analysis, Chemistry & Radiochemistry, PET/CT Imaging and CBR pharmacology.

Research Team:

Principal Investigator:

Piero Salvadori