Molecular imaging of early αvß3 integrin expression predicts long-term left-ventricle remodeling after myocardial infarction in rats.

UNLABELLED: (18)F-galacto-RGD ((18)F-RGD) is a PET tracer binding to α(v)ß(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)ß(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). CONCLUSION: 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)ß(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.

Simplified quantification of myocardial flow reserve with flurpiridaz F 18: validation with microspheres in a pig model.

UNLABELLED: The novel PET flow tracer flurpiridaz F 18 shows high myocardial extraction and slow washout. flurpiridaz F 18 PET data analysis with tracer kinetic modeling provides accurate absolute myocardial blood flow (MBF) measurements but requires in-scanner injection and complex processing. We evaluated the hypothesis that myocardial retention and standardized uptake values (SUVs) based on late uptake provide accurate estimates of myocardial flow reserve (MFR) and, thus, might allow simplified quantification after tracer injection outside the scanner. METHODS: Nine pigs had dynamic PET scans after repeated injections of flurpiridaz F 18 at rest and combined adenosine and dobutamine stress. flurpiridaz F 18 PET with a 3-compartment model and coinjected radioactive microspheres were used to delineate MBF. These quantitative measurements were compared with myocardial retention (%/min) and SUV of flurpiridaz F 18 after summing data over 5-10, 5-12, 5-15, 10-15, and 10-20 min after tracer injection. RESULTS: MBF ranged from 0.5 to 2.8 mL/min/g. There was a good correlation between both flurpiridaz F 18 retention and SUVs from 5 to 12 min after injection and MBF measured using 3-compartment model- or microsphere-derived MBF (r = 0.73, P < 0.05, and r = 0.68, P < 0.05, respectively, for retention; r = 0.88, P < 0.001, and r = 0.92, P < 0.001, respectively, for SUV). At later time points, retention and SUV underestimated stress microsphere flow (at 10-20 min: r = 0.41, P = not significant, and r = 0.46, P = not significant, respectively, for retention; r = 0.41, P = not significant, and r = 0.65, P < 0.05, respectively, for SUV). When measured 5-12 min after injection, there was a close agreement between MFR measured with either flurpiridaz F 18 retention or SUV and MFR measured using microspheres (mean difference, -0.08 ± 0.36 and -0.18 ± 0.25, respectively). CONCLUSION: Myocardial retention and SUVs of the (18)F-labeled flow tracer flurpiridaz F 18 accurately reflect the MFR. These simplified analysis methods may facilitate the combination of quantitative assessment of perfusion reserve and rapid clinical imaging protocols.

Evaluation of a novel (18)F-labeled positron-emission tomography perfusion tracer for the assessment of myocardial infarct size in rats.

BACKGROUND: The goal of this study was to evaluate a new (18)F-labeled positron-emission tomography (PET) perfusion tracer, (18)F BMS747158-02, for the assessment of myocardial infarct (MI) size. METHODS AND RESULTS: Wistar rats were studied 24 hours after ligation of the left coronary artery either permanently (n=15) or transiently (n=16) for 30 minutes. Seven nonoperated rats were studied as controls. The rats were injected with 37 MBq of (18)F BMS747158-02 and imaged with a small animal PET scanner for 20 minutes. Polar maps were generated for measurement of PET defect size, and left ventricular systolic and diastolic volumes were assessed in gated images. As a reference, MI size was determined by 2,3,5-triphenyltetrazolium chloride staining of left ventricular tissue samples. Permanent or transient ligation of the left coronary artery produced transmural or subendocardial MI of variable sizes, respectively. In normal rats, PET imaging demonstrated intense and homogeneous uptake of (18)F BMS747158-02 throughout the myocardium. After ligation, sharply defined perfusion defects were present. Throughout the imaging period, the defect size correlated closely with the MI size either after permanent (r=0.88; P<0.01; mean difference, 1.86%) or transient (r=0.92; P<0.01; mean difference, 2.16%) ligation of the left coronary artery. Moreover, reduction of left ventricular systolic function measured with PET correlated with the MI size (r=-0.81; P<0.01; n=23). CONCLUSIONS: Myocardial (18)F BMS747158-02 PET imaging provides excellent image quality and uptake properties, enabling accurate evaluation of MI size and left ventricular function in rats. It is a promising technique for evaluation of MI size in clinical trials.