Briard, Emmanuelle, Rudolph, Bettina, Desrayaud, Sandrine, Krauser, Joel and Auberson, Yves (2015) MS565, a SPECT tracer for evaluating the brain penetration of BAF312 (siponimod). ChemMedChem, 10 (6). pp. 1008-1018. ISSN 18607179

Abstract

BAF312 (siponimod) is a sphingosine 1-phosphate (S1P) receptor modulator in clinical development for the treatment of multiple sclerosis, with faster organ distribution and elimination kinetics than its precursor FTY720 (Gilenya®). Our aim was to better quantify the penetration of BAF312 in the human brain, after labeling with a radioisotope for positron emission tomography (PET) or single photon emission computer tomography (SPECT). The radioisotopes 11C and 18F, which could have been introduced in BAF312 without modifying its structure, do not have decay kinetics compatible with the time required for observing the organ distribution of the drug in patients. In contrast, we identified a longer-lived iodinated derivative of BAF312 (18, MS565), which retains the blood pharmacokinetics and organ distribution of the original molecule as well as its affinity, selectivity for S1P receptors, and overall physicochemical properties. MS565 can easily be radiolabeled with 123I for SPECT or 124I for PET imaging. [123I]MS565 is currently under development as a clinical imaging agent.

Item Type:	Article
Keywords:	Siponimod, SPECT, PET, myelin, imaging agents, 123-iodine
Date Deposited:	26 Apr 2016 23:45
Last Modified:	26 Apr 2016 23:45
URI:	https://oak.novartis.com/id/eprint/25036