PT - JOURNAL ARTICLE AU - Eric Petrie AU - John Grierson AU - Donna Cross AU - Atsushi Obata AU - Barbara Lewellen AU - Satoshi Minoshima TI - Initial PET evaluation of [F-18]fluoro-HEAT for central alpha-1 noradrenergic receptor imaging DP - 2010 May 01 TA - Journal of Nuclear Medicine PG - 107--107 VI - 51 IP - supplement 2 4099 - http://jnm.snmjournals.org/content/51/supplement_2/107.short 4100 - http://jnm.snmjournals.org/content/51/supplement_2/107.full SO - J Nucl Med2010 May 01; 51 AB - 107 Objectives Alpha-1 noradrenergic receptors are thought to contribute to the pathophysiology of anxiety symptoms in patients with post-traumatic stress disorder (PTSD) and disruptive agitation associated with Alzheimer’s Disease. We investigated [F-18]fluoro-HEAT, a central alpha-1 nAR antagonist, as a potential PET imaging agent. Methods [F-18]Fluoro-HEAT was produced via a 4-step reaction sequence using teralone-2-OTf, [F-18]fluoride, formaldehyde and tyramine. Fluoro-HEAT was screened for binding potency against adrenergic and serotonergic receptors in vitro. [F-18]Fluoro-HEAT biodistribution was confirmed in rat imaging and tissue counting (n=3). Displacement studies were conducted using prazosin and Fluoro-HEAT with non-human primates (n=3). Results [F-18]F-HEAT was prepared in 6%, decay corrected yield within 180-220 min. F-HEAT was non-sub-type selective for cloned human alpha-1(A,B,D) receptors with IC50 values: 19, 28, 19 nM, respectively. 5-HT(2a, 5a,7) receptors did not bind F-HEAT (IC50 >200 nM). Rat PET imaging showed rapid tracer uptake by the brain (6 minutes) followed by bi-exponential washout with estimated relative distribution volume of 1.2-1.4 in the brain (Logan Plot). Non-human primate PET studies with [F-18]Fluoro-HEAT using a bolus + infusion protocol and drug displacement by prazosin or Fluoro-HEAT showed displacements of 4-5% and 3-9% binding, respectively. Conclusions [F-18]fluoro-HEAT appears to have promising characteristics for central alpha-1 noradrenergic receptor imaging. Further investigations with the tracer synthesis and dosimetry studies are ongoing. Research Support US Department of Veterans Affairs and NIH K08-AG023670