Novel molecular imaging compounds that detect neuroinflammation in the brain of multiple sclerosis (MS) patients have been developed by researchers at the Washington University School of Medicine in Missouri, and may help to uncover the triggers of such inflammation and to better evaluate new disease treatments.
The study, “Development and in vivo evaluation of three F-18 labeled S1P1 ligands as PET tracers for MS,” was recently presented at the 2016 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting in San Diego, California.
“Inflammation is the body’s physiological defense to harmful stimuli and it plays a critical role in the immune response to injury and infection,” Zhude Tu, PhD, a professor of PET radiochemistry at Washington and the study’s senior author, said in a press release. “However, despite the benefits of acute inflammation in promoting healing, these same processes are associated with numerous pathological conditions when chronic inflammation is left unchecked.”
The current first-line therapy for relapsing-remitting MS is fingolimod (Gilenya), a drug that acts through the sphingosine 1-phosphate receptor 1 (S1P1), and sequestrates immune cells in lymph nodes away from the central nervous system, reducing their potential to damage the myelin layer. Because S1P1 is highly expressed under neuroinflammatory conditions, the authors thought it would be a good biomarker for the detection of inflammatory processes in MS patients.
Adam J. Rosenberg, PhD, the study’s first author, and colleagues produced a library of radiolabeled small molecules that targeted S1P1. The molecules, labeled with fluorine-18, could be imaged with preclinical positron emission tomography (PET), a methodology widely used in the clinic.
Researchers found that PET imaging agents had the ability to cross the blood brain barrier, which is often a limiting factor in central nervous system drugs. These agents could detect the increase of S1P1 expression in a mice model of MS, suggesting that they may be promising PET tracers to detect inflammatory responses in the brains of MS patients or those with other inflammatory diseases.
“These compounds represent promising PET tracers for imaging MS and other inflammatory diseases by quantitative assessment of S1P1 expression in the body,” Dr. Tu concluded.
MS, a neurodegenerative disease, is estimated to affect more than 2.3 million people worldwide. It is characterized by inflammatory processes that lead to the degradation of the myelin sheaths that surround nerve cells to protect them and increase the speed of nerve impulses.
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