Author + information
- Received July 31, 2006
- Accepted August 30, 2006
- Published online November 21, 2006.
- Bettina Wagner, DVM⁎,
- Martina Anton, PhD†,
- Stephan G. Nekolla, PhD⁎,
- Sybille Reder, MT⁎,
- Julia Henke, DVM†,
- Stefan Seidl, MD‡,
- Renate Hegenloh, MT§,
- Masao Miyagawa, MD⁎,
- Roland Haubner, PhD⁎,
- Markus Schwaiger, MD⁎ and
- Frank M. Bengel, MD⁎∥,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Frank M. Bengel, Division of Nuclear Medicine, Russell H. Morgan Department of Radiology, Johns Hopkins University Medical Institutions, 601 N. Caroline Street, JHOC 3225, Baltimore, Maryland 21287.
Objectives 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 VEGF121gene 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 αvβ3integrin 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 αvβ3integrin adhesion molecules early after the intervention.
Supported by a grant from the Deutsche Forschungsgemeinschaft (Be 2217/4-1).
- Received July 31, 2006.
- Accepted August 30, 2006.
- American College of Cardiology Foundation