PREPARATION OF 4-[BR-76]BROMOMETARAMINOL AND 6-[BR-76]BROMOMETARAMINOL, 2 POTENTIAL RADIOTRACERS FOR THE STUDY OF THE MYOCARDIAL NOREPINEPHRINE NEURONAL REUPTAKE SYSTEM WITH PET

Metaraminol is a norepinephrine analogue which is transported with hig h affinity by the uptake-1 mechanism of the sympathetic nerve terminal . Radiolabelled metaraminol and analogues are promising radiotracers t o assess the integrity of the myocardial nerve system. The bromo analo gues, 4- and 6-bromometaraminol, were synthesized from commercially av ailable metaraminol bitartrate. Structural assignments were made by PD -NMR experiments. 4- and 6-[Br-76]Bromometaraminol were prepared from N-Boc-metaraminol using [Br-76]NH4Br and peracetic acid as the bromina ting agent. The total radiochemical yield based on starting [Br-76]NH4 Br was 17% and 38%, non decay-corrected, for derivative 4-[Br-76]bromo metaraminol and 6-[Br-76]bromometaraminol, respectively, in a synthesi s time of 3.5 hours including the preparation of [Br-76]NH4Br. The spe cific radioactivity obtained for both radiotracers was 130 mCi/mu mol (4.8 GBq/mu mol). Tissue distribution studies were performed in rats a nd revealed a low cardiac uptake for both derivatives. These prelimina ry results suggest that neither 4- nor 6-[Br-76]bromometaraminol are s uitable radiotracers to study the myocardial norepinephrine neuronal r euptake system with Positron Emission Tomography.