title: Molecular hybrid positron emission tomography/computed tomography imaging of cardiac angiotensin II type 1 receptors.
abstract: OBJECTIVE
  The goal of this study was to explore the feasibility of targeted imaging of the angiotensin II type 1 receptor (AT1R) in cardiac tissue, using clinical hybrid positron emission tomography/computed tomography (PET/CT).
  
  
  BACKGROUND
  AT1R is an attractive imaging target due to its key role in various cardiac pathologies, including post-infarct left ventricular remodeling.
  
  
  METHODS
  Using the novel AT1R ligand [(11)C]-KR31173, dynamic PET/CT was performed in young farm pigs under healthy conditions (n = 4) and 3 to 4 weeks after experimental myocardial infarction (n = 5). Ex vivo validation was carried out by immunohistochemistry and polymerase chain reaction. First-in-man application was performed in 4 healthy volunteers at baseline and under AT1R blocking.
  
  
  RESULTS
  In healthy pigs, myocardial KR31173 retention was detectable, regionally homogeneous, and specific for AT1R, as confirmed by blocking experiments. Metabolism in plasma was low (85 ± 2% of intact tracer after 60 min). After myocardial infarction, KR31173 retention, corrected for regional perfusion, revealed AT1R up-regulation in the infarct area relative to remote myocardium, whereas retention was elevated in both regions when compared with myocardium of healthy controls (8.7 ± 0.8% and 7.1 ± 0.3%/min vs. 5.8 ± 0.4%/min for infarct and remote, respectively, vs. healthy controls; p < 0.01 each). Postmortem analysis confirmed AT1R up-regulation in remote and infarct tissue. First-in-man application was safe, and showed detectable and specific myocardial KR31173 retention, albeit at a lower level than pigs (left ventricular average retention: 1.2 ± 0.1%/min vs. 4.4 ± 1.2%/min for humans vs. pigs; p = 0.04).
  
  
  CONCLUSIONS
  Noninvasive imaging of cardiac AT1R expression is feasible using clinical PET/CT technology. Results provide a rationale for broader clinical testing of AT1R-targeted molecular imaging.
authors.affiliation: Division of Nuclear Medicine, Russell H. Morgan Department of Radiology, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Kenji
authors.initials: K
authors.lastname: Fukushima
authors.forename: Paco E
authors.initials: PE
authors.lastname: Bravo
authors.forename: Takahiro
authors.initials: T
authors.lastname: Higuchi
authors.forename: Karl H
authors.initials: KH
authors.lastname: Schuleri
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Lin
authors.forename: M Roselle
authors.initials: MR
authors.lastname: Abraham
authors.forename: Jinsong
authors.initials: J
authors.lastname: Xia
authors.forename: William B
authors.initials: WB
authors.lastname: Mathews
authors.forename: Robert F
authors.initials: RF
authors.lastname: Dannals
authors.forename: Albert C
authors.initials: AC
authors.lastname: Lardo
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szabo
authors.forename: Frank M
authors.initials: FM
authors.lastname: Bengel
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D064847:Multimodal Imaging; D009203:Myocardial Infarction / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D049268:Positron-Emission Tomography; D044140:Receptor, Angiotensin, Type 1; D013552:Swine; D014057:Tomography, X-Ray Computed; D015854:Up-Regulation
chemical_list: D044140:Receptor, Angiotensin, Type 1