title: Noninvasive characterization of myocardial molecular interventions by integrated positron emission tomography and computed tomography.
abstract: OBJECTIVE
  We sought to investigate the usefulness of integrated positron emission tomography (PET) and computed tomography (CT) for in vivo characterization of an angiogenesis-directed molecular intervention.
  
  
  BACKGROUND
  Controversies about the effectiveness of molecular therapies for cardiovascular disease have prompted the need for more powerful noninvasive imaging techniques.
  
  
  METHODS
  In a model of regional adenoviral transfer of the VEGF(121) gene to myocardium of healthy pigs, PET-CT using multiple molecular-directed radiotracers was employed.
  
  
  RESULTS
  Two days after gene transfer, successful transgene expression was noninvasively confirmed by a reporter probe targeting co-expressed HSV1-sr39tk reporter gene. The CT-derived ventricular function and morphology remained unaltered (left ventricular ejection fraction 57 +/- 5% in adenovirus-injected animals vs. 53 +/- 5% in controls; p = 0.36). Increased regional perfusion was identified in areas overexpressing VEGF (myocardial blood flow during adenosine-induced vasodilation 1.47 +/- 0.49 vs. 1.14 +/- 0.27 ml/g/min in remote areas; p = 0.01), corroborating in vivo effects on microvascular tone and permeability. Finally, regional angiogenesis-associated alpha(v)beta3 integrin expression was not enhanced, suggesting little contribution to the perfusion increase. Fusion of CT morphology and tracer-derived molecular signals allowed for accurate regional localization of biologic signals. Findings were validated by control vectors, sham-operated animals, and ex vivo tissue analysis.
  
  
  CONCLUSIONS
  Integrated PET-CT has the potential to dissect cardiovascular biologic mechanisms from gene expression to physiologic function and morphology. The VEGF overexpression in healthy myocardium increases myocardial perfusion without significant up-regulation of alpha(v)beta3 integrin adhesion molecules early after the intervention.
authors.affiliation: Nuklearmedizinische Klinik und Poliklinik, Technische Universität München, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Wagner
authors.forename: Martina
authors.initials: M
authors.lastname: Anton
authors.forename: Stephan G
authors.initials: SG
authors.lastname: Nekolla
authors.forename: Sybille
authors.initials: S
authors.lastname: Reder
authors.forename: Julia
authors.initials: J
authors.lastname: Henke
authors.forename: Stefan
authors.initials: S
authors.lastname: Seidl
authors.forename: Renate
authors.initials: R
authors.lastname: Hegenloh
authors.forename: Masao
authors.initials: M
authors.lastname: Miyagawa
authors.forename: Roland
authors.initials: R
authors.lastname: Haubner
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
authors.forename: Frank M
authors.initials: FM
authors.lastname: Bengel
mesh_terms: D000818:Animals; D003326:Coronary Circulation; D005240:Feasibility Studies; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D006321:Heart / Q000000981:diagnostic imaging* / Q000502:physiology; D018259:Herpesvirus 1, Human / Q000201:enzymology; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D009154:Mutation; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D049268:Positron-Emission Tomography; D013552:Swine; D013937:Thymidine Kinase / Q000235:genetics; D014057:Tomography, X-Ray Computed; D019076:Transgenes; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D039302:Integrin alphaVbeta3; D042461:Vascular Endothelial Growth Factor A; D013937:Thymidine Kinase