Molecular imaging of early αvβ3 integrin expression predicts long-term left-ventricle remodeling after myocardial infarction in rats.
(18)F-galacto-RGD ((18)F-RGD) is a PET tracer binding to α(v)β(3) integrin receptors that are upregulated after myocardial infarction (MI) as part of the healing process. We studied whether myocardial (18)F-RGD uptake early after MI is associated with long-term left-ventricle (LV) remodeling in a rat model.


METHODS
Wistar rats underwent sham operation (n = 9) or permanent coronary ligation (n = 25). One week after MI, rats were injected with (18)F-RGD to evaluate α(v)β(3) integrin expression using a preclinical PET system. In the same rats, LV volumes and defect size were measured 1 and 12 wk after MI by (13)N-ammonia PET and MRI, respectively.


RESULTS
One week after MI, (18)F-RGD uptake was increased in the defect area as compared with the remote myocardium of MI rats or sham-operated controls (percentage injected dose per cubic centimeter, 0.20 ± 0.05 vs. 0.06 ± 0.03 and 0.07 ± 0.04, P < 0.001). At this time, (18)F-RGD uptake was associated with capillary density in histologic sections. Average (18)F-RGD uptake in the defect area was lowest in the rats demonstrating greater than 20% relative increase in the LV end-diastolic volume from 1 to 12 wk (percentage injected dose per centimeter cubed, 0.15 ± 0.07 vs. 0.21 ± 0.05, P < 0.05). In a multivariable logistic regression analysis, low (18)F-RGD uptake was a significant predictor of increase in end-diastolic volume (r = 0.51, P < 0.05).


CONCLUSIONS
High levels of (18)F-RGD uptake in the perfusion defect area early after MI were associated with the absence of significant LV remodeling after 12 wk of follow-up. These results suggest that α(v)β(3) integrin expression is a potential biomarker of myocardial repair processes after MI and enables the monitoring of these processes by molecular imaging to derive possible prognostic information.
Nuklearmedizinische Klinik, Technischen Universität München, Munich, Germany. hossam_sherif_66@hotmail.com
Hossam M
HM
Sherif
Antti
A
Saraste
Stephan G
SG
Nekolla
Eliane
E
Weidl
Sybille
S
Reder
Arne
A
Tapfer
Martina
M
Rudelius
Takahiro
T
Higuchi
René M
RM
Botnar
Hans-Jürgen
HJ
Wester
Markus
M
Schwaiger
D000818:Animals; D001692:Biological Transport; D005690:Galactose / Q000031:analogs & derivatives / Q000378:metabolism; D005786:Gene Expression Regulation; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D009203:Myocardial Infarction / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010456:Peptides, Cyclic / Q000378:metabolism; D049268:Positron-Emission Tomography; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000378:metabolism*; D020257:Ventricular Remodeling
D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; C423503:fluorogalacto-RGD; D005690:Galactose