Sviluppo di nuovi radiotraccianti PET marcati con ¹⁸F per l'imaging della glicoproteina P, dei recettori sigma e dei recettori cannabinoidi di sottotipo 2 nel sistema nervoso centrale.

Positron emission tomography (PET) is a diagnostic imaging technique that enables the sensitive and noninvasive detection and quantification of receptors and enzymes using positron-emitting radionuclides, such as 18F. Several biomarkers have been identified for the early diagnosis of neurodegenerative diseases, including P-glycoprotein (P-gp), sigma receptors, subdivided into sigma-1 (S1R) and sigma-2 (S2R) and cannabinoid receptor subtype 2 (CB2R). The Italian Medicines Agency (AIFA) has approved P-gp as a target for the initiation of a Phase II clinical trial investigating drug-resistant, P-gp-associated major depression. A structure–affinity relationship (SAfiR) study was conducted on S1R, S2R, and CB2R to identify novel PET radiotracers. For S1R, a new radiotracer was identified, successfully radiolabeled, and evaluated by in vitro autoradiography, where it exhibited high affinity and a distribution consistent with the known presence of S1R in the central nervous system. For CB2R, two PET radiotracers with opposing pharmacological activities were identified. Although radiolabeling was successful, the autoradiographic data remain preliminary. In contrast, no suitable PET radiotracer was identified for S2R; however, the most promising compound displayed dual S1R/S2R activity, suggesting potential utility as a neuroprotective agent.