Imagenología por PET dirigida a S1PR: Avances en la comprensión de patologías neuroinflamatorias e inmunomediadas

Sphingosine-1-phosphate (S1P) and its receptors (S1PRs) are pivotal regulators of immune cell trafficking, vascular integrity, and various physiological processes, playing key roles in the pathogenesis of neuroinflammatory and immune-related disorders. Among these, multiple sclerosis (MS) is the most common chronic inflammatory condition affecting the central nervous system (CNS), marked by autoimmune-induced neurodegeneration, inflammation, and ongoing demyelination. FTY720, known as fingolimod or Gilenya, is an immunomodulatory medication that was approved in 2010 as the first oral therapy for relapsing-remitting MS. Upon phosphorylation, FTY720 mimics S1P and binds selectively to all S1PR subtypes, except S1PR2, underscoring the therapeutic possibilities of focusing on the S1P-S1PR signaling axis for neuroinflammatory conditions. This success emphasizes the relevance of S1P-mediated pathways in both disease mechanisms and treatment strategies. Emerging precision medicine approaches emphasize the importance of noninvasive imaging to elucidate molecular mechanisms in vivo. Positron emission tomography (PET) imaging-utilizing suitable radioactive tracers to probe biological targets and processes in vivo-offers a transformative approach to quantifying receptor expression, thereby delineating crucial insights into disease diagnosis, therapy monitoring, and therapeutic drug development. As such, S1PR-specific PET imaging provides a promising approach to explore the pivotal role of S1PRs in MS and other immune-mediated diseases. This review offers a comprehensive overview of the development and clinical applications of S1PR-targeted PET radiopharmaceuticals, illustrating their potential to transform therapeutic strategies. Further, recent advances in radiopharmaceutical design have yielded S1PR-targeted PET probes with high specificity, improved metabolic stability, and enhanced blood-brain barrier penetration, addressing key challenges in imaging neuroinflammation. Additionally, it critically discusses future directions for S1PR-targeted PET imaging in advancing our understanding of disease mechanisms, improving patient outcomes, and contributing to the broader vision of precision medicine.