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Noninvasive characterization of myocardial molecular interventions by integrated positron emission tomography and computed tomography.

Abstract：

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 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.

journal_name

J Am Coll Cardiol

journal_title

Journal of the American College of Cardiology

authors

Wagner B,Anton M,Nekolla SG,Reder S,Henke J,Seidl S,Hegenloh R,Miyagawa M,Haubner R,Schwaiger M,Bengel FM

doi

10.1016/j.jacc.2006.08.029

subject

Has Abstract

pub_date

2006-11-21 00:00:00

pages

2107-15

issue

eissn

0735-1097

issn

1558-3597

pii

S0735-1097(06)02267-4

journal_volume

pub_type

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Noninvasive characterization of myocardial molecular interventions by integrated positron emission tomography and computed tomography.