Assessment of alphavbeta3 integrin expression after myocardial infarction by positron emission tomography.
OBJECTIVE
The purpose of this study was to determine the feasibility of a new positron emission tomography (PET) imaging approach using an (18)F-labelled alpha(v)beta(3) integrin antagonist ((18)F-Galacto-RGD) to monitor the integrin expression after myocardial infarction.


RESULTS
Male Wister rats were subjected to 20 min transient left coronary artery occlusion followed by reperfusion. Autoradiographic analysis and in vivo PET imaging were used to determine myocardial (18)F-Galacto-RGD uptake at different time points following reperfusion.


RESULTS
PET imaging and autoradiography demonstrated no significant focal myocardial (18)F-Galacto-RGD uptake in non-operated control rats and at day 1 after reperfusion. However, focal accumulation in the infarct area started at day 3 (uptake ratio = 1.91 +/- 0.22 vs. remote myocardium), peaked between 1 (3.43 +/- 0.57) and 3 weeks (3.43 +/- 0.95), and decreased to 1.96 +/- 0.40 at 6 months after reperfusion. Pretreatment with alpha(v)beta(3) integrin antagonist c(-RGDfV-) significantly decreased tracer uptake, indicating the specificity of tracer uptake. The time course of focal tracer uptake paralleled vascular density as measured by CD31 immunohistochemical analysis.


CONCLUSIONS
Regional (18)F-Galacto-RGD accumulation suggests up-regulation of alpha(v)beta(3) integrin expression after myocardial infarction, which peaks between 1 and 3 weeks and remains detectable until 6 months after reperfusion. This new PET tracer is promising for the monitoring of myocardial repair processes.
Higuchi
Takahiro
T
Nuklearmedizinische Klinik und Poliklinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger Strasse 22, 81675 Munich, Germany. higuchi@po2.nsknet.or.jp
Bengel
Frank M
FM
Seidl
Stefan
S
Watzlowik
Petra
P
Kessler
Horst
H
Hegenloh
Renate
R
Reder
Sybille
S
Nekolla
Stephan G
SG
Wester
Hans J
HJ
Schwaiger
Markus
M
D000818:Animals; D001345:Autoradiography; D003331:Coronary Vessels / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005690:Galactose / Q000031:analogs & derivatives / Q000378:metabolism; D007150:Immunohistochemistry; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D018919:Neovascularization, Physiologic; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019275:Radiopharmaceuticals; C092113:cyclo(arginyl-glycyl-aspartyl-phenylalanyl-valyl); C423503:fluorogalacto-RGD; D005690:Galactose