RT Journal Article
SR Electronic
T1 Initial PET evaluation of [F-18]fluoro-HEAT for central alpha-1 noradrenergic receptor imaging
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 107
OP 107
VO 51
IS supplement 2
A1 Eric Petrie
A1 John Grierson
A1 Donna Cross
A1 Atsushi Obata
A1 Barbara Lewellen
A1 Satoshi Minoshima
YR 2010
UL http://jnm.snmjournals.org/content/51/supplement_2/107.abstract
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