title: BZM055, an iodinated radiotracer candidate for PET and SPECT imaging of myelin and FTY720 brain distribution.
abstract: FTY720 (fingolimod, Gilenya®) is a sphingosine 1-phosphate (S1P) receptor modulator that shows significant therapeutic efficacy after oral administration to patients of multiple sclerosis. Because FTY720 does not contain any atom whose PET or SPECT radioisotope would have a half-life compatible with its pharmacokinetic properties, it cannot be used directly for imaging. Instead, we propose BZM055 as a surrogate tracer to study its pharmacokinetics and organ distribution in patients and, given that FTY720 accumulates in myelin sheaths, for myelin imaging. BZM055 (2 a, 2-iodo-FTY720) can be easily radiolabeled with ¹²³I (for SPECT) or ¹²⁴I (for PET). Not only does it closely mimic the pharmacokinetics and organ distribution of FTY720, but also its affinity, selectivity for S1P receptors, phosphorylation kinetics, and overall physicochemical properties. [¹²³I]BZM055 is currently under development for clinical imaging.
authors.affiliation: Novartis Institutes for BioMedical Research, Basel, Global Discovery Chemistry, Neurosciences and Molecular Imaging, Postfach, 4002 Basel, Switzerland. emmanuelle.briard@novartis.com
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Briard
authors.forename: David
authors.initials: D
authors.lastname: Orain
authors.forename: Christian
authors.initials: C
authors.lastname: Beerli
authors.forename: Andreas
authors.initials: A
authors.lastname: Billich
authors.forename: Markus
authors.initials: M
authors.lastname: Streiff
authors.forename: Marc
authors.initials: M
authors.lastname: Bigaud
authors.forename: Yves P
authors.initials: YP
authors.lastname: Auberson
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry; D007700:Kinetics; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology; D009186:Myelin Sheath / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D049268:Positron-Emission Tomography / Q000379:methods*; D011859:Radiography; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D007457:Iodine Radioisotopes; D049349:Receptors, Lysosphingolipid