Preparation of 4- and 6-[76Br]bromometaraminol, two potential radiotracers for the study of the myocardial norepinephrine neuronal reuptake system with PET

Article abstract of DOI:10.1002/(SICI)1099-1344(199710)39:10<803::AID-JLCR27>3.0.CO;2-R

Metaraminol is a norepinephrine analogue which is transported with high affinity by the uptake-1 mechanism of the sympathetic nerve terminal. Radiolabelled metaraminol and analogues are promising radiotracers to assess the integrity of the myocardial nerve system. The bromo analogues, 4- and 6-bromometaraminol, were synthesized from commercially available metaraminol bitartrate. Structural assignments were made by 2D-NMR experiments. 4- and 6-[⁷⁶Br]Bromometaraminol were prepared from N-Boc-metaraminol using [⁷⁶Br]NH₄Br and peracetic acid as the brominating agent. The total radiochemical yield based on starting [⁷⁶Br]NH₄Br was 17% and 38%, non decay-corrected, for derivative 4-[⁷⁶Br]bromometaraminol and 6-[⁷⁶Br]bromometaraminol, respectively, in a synthesis time of 3.5 hours including the preparation of [⁷⁶Br]NH₄Br. The specific radioactivity obtained for both radiotracers was 130 mCi/μmol (4.8 GBq/μmol). Tissue distribution studies were performed in rats and revealed a low cardiac uptake for both derivatives. These preliminary results suggest that neither 4- nor 6-[⁷⁶Br]bromometaraminol are suitable radiotracers to study the myocardial norepinephrine neuronal reuptake system with Positron Emission Tomography.