(±)‐N‐[ 11 C]Methyl‐ para ‐hydroxytranylcypromine: Synthesis and evaluation as a pet radiotracer for quantifying cardiac sympathetic nerve density

Our laboratory has previously developed several radiotracers that can be used to noninvasively assess regional cardiac sympathetic nerve integrity in the living human, including radioiodinated meta-iodobenzylguanidine (MIBG) for single-photon imaging studies' and ["C]meta-hydroxyephedrine (HED) for PET imaging studies2. However, the kinetic properties of the current generation of neuronal imaging agents are not conducive to quantitative analysis with compartmental modeling techniques, which limits our ability to obtain sensitive measures of neuronal density. In an effort to develop a sympathetic nerve tracer with more favorable kinetic properties for compartmental modeling, we synthesized a "C-labeled analog of tranyl~ypromine~ (TCP), a suicide inhibitor of monoamine oxidase (MAO) that is also a substrate for neuronal uptake by the norepinephrine transporter (NET). In principle, a NET substrate that is transpoited into sympathetic neurons more slowly than HED and is . subsequently trapped intraneuronally by a rapid and irreversible binding process would possess ideal kinetic properties for absolute quantification of neuronal density.