Z-(-,-)-[BR-76]BRQNP - A HIGH-AFFINITY PET RADIOTRACER FOR CENTRAL AND CARDIAC MUSCARINIC RECEPTORS

Racemic E-1-azabicyclo[2.2.2]oct-3-yl 1-1-propen-3-yl)-alpha-hydroxy-a lpha-phenylacetate (BrQNP) was prepared and evaluated in vivo as a pot ential candidate for imaging muscarinic acetylcholinergic receptors by Positron Emission Tomography. Initial in vivo blocking studies utiliz ing Z-(-,-)-[I-125]IQNP as a radiolabelled muscarinic probe demonstrat ed that a preinjection of cold E-BrQNP effectively blocks the uptake o f the radiolabelled probe in the brain and heart, by 71% and 86% respe ctively. Z-(-,-)-[Br-76]BrQNP was prepared by electrophillic substitut ion from a tributylstannyl precursor. Peracetic acid and chloramine T were evaluated as oxidizing agents. After purification by SPE and RP-H PLC, radiolabelling yields of 85% and 95% were obtained with peracetic acid and chloramine T, respectively. The final radiochemical yield wa s 70% for both oxidizing agents. Rat biodistribution studies of Z-(-,- )-[Br-76]BrQNP showed high uptake in organs with high concentrations o f muscarinic receptors (heart and brain).