Evaluation of the superselective radioligand [123I]PE2I for imaging of the dopamine transporter in SPECT: PhD Thesis

Imaging of the dopamine transporter (DAT) with Single Photon Emission Computer Tomography (SPECT) has increasingly been used as a biomarker for the integrity of presynaptic dopaminergic nerve cells in patients with movement disorders. 123-I-labelled N-(3-iodoprop-2E-enyl)-2-β-carbomethoxy-3β-(4-methylphenyl) nortropane, named PE2I, is a relatively new radioligand that has about 10-fold higher in vitro selectivity for the DAT than for the serotonin transporter (SERT) compared to the slightly older but very used and licensed radioligand [123I]FP-CIT (DaTSCAN). Further [123I]PE2I has faster kinetics than [123I]FP-CIT. Because of its fast kinetic properties, quantification of [123I]PE2I binding to DAT is possible using kinetic or graphical analysis following bolus injection of tracer or as a combination of bolus and constant infusion. Based on preliminary bolus trials we have been able to calculate a B/I ratio of [123I]PE2I. This B/I ratio (2.7h) gave rise to steady state conditions and excellent reproducibility. Further, manual delineation of ROI directly on SPECT images performed equally well to a MRI-defined probability map based ROI delineation in terms of intrasubject variability of binding potential of DAT. Finally the in vivo SERT binding in DAT images obtained with [123I]FP-CIT was significant as compared to the [123I]PE2I image. [123I]PE2I is a super selective SPECT DAT radioligand with optimal kinetic properties for accurate quantification of the DAT availability in striatum. Apart from the more laborious B/I design it is currently to be considered the best radioligand for imaging the DAT in the human brain with SPECT.