BZM055, an Iodinated Radiotracer Candidate for PET and SPECT Imaging of Myelin and FTY720 Brain Distribution

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. Improve your image: FTY720 (fingolimod, Gilenya®) is an orally active S1P receptor modulator for the treatment of multiple sclerosis. 2‐Iodo‐FTY720 (BZM055) is proposed as a PET or SPECT tracer to study the pharmacokinetics and brain penetration of FTY720 in patients. Because this drug accumulates in myelin sheaths, [123I]‐ or [124I]BZM055 might also prove useful to image myelin in patients.