Carlo Reale
Ciclo: XL
Data inizio: 1/10/2024
Curriculum: Farmaceutiche
Borsa: UniCT
Titolo tesi: PET Radiotracer Development for Delta-Opioid Receptor Mapping in Neuropathic Pain
Abstract: Neuropathic pain is a complex condition characterized by damage or dysfunction of the somatosensory system, leading to central and peripheral sensitization, maladaptive plasticity, and chronic neuroinflammation. Because traditional treatments and mu-opioid receptor (MOR) agonists often suffer from limited efficacy or severe side effects—such as tolerance and dependence—the delta-opioid receptor (DOR) has emerged as a critical target for innovative pain management.
This research project focuses on the design and synthesis of novel ligands specifically engineered to map DOR distribution and function through positron emission tomography (PET) imaging. While endogenous peptides and their analogues have been used to study DOR, their utility is often restricted by low metabolic stability and poor permeability across the blood-brain barrier. To address these limitations, this project emphasizes the development of synthetic small-molecule derivatives, specifically centering on the optimization of SNC-80.
The core of the study involves the following phases:
1. Ligand Design and Synthesis: the development of a fluorinated SNC-80 derivative (Compound 5), which maintains a high binding affinity for the receptor.
2. Radiochemical Development: the design and radiosynthesis of an 18F-labeled tracer. The choice of 18F over 11C is driven by its longer half-life, which provides a more practical window for synthesis and subsequent administration in experimental models.
3. Validation: comprehensive evaluation through in vitro competition binding assays and in vivo microPET/CT imaging in both healthy and neuropathic pain rat models to assess tracer distribution under physiological and pathological states.
Ultimately, the development of these novel DOR-targeted imaging agents aims to provide a powerful tool for the diagnosis and monitoring of neuropathic pain. Beyond pain management, these tracers possess significant potential for broader applications, including drug screening, investigating cancer-related pain, and enhancing our understanding of the opioid system's role in psychiatric disorders like anxiety and depression.
Tutor: Pasquinucci
Data Conseguimento Titolo: in corso
Linkedin: www.linkedin.com/in/carlo-reale-b581b97b
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