In vivo molecular imaging of myocardial angiogenesis using the αvβ3 integrin-targeted tracer 99mTc-RAFT-RGD

Abstract

BackgroundMyocardial angiogenesis following reperfusion of an infarcted area may impact on patient prognosis and pro-angiogenic treatments are currently evaluated. The non-invasive imaging of angiogenesis would therefore be of potential clinical relevance in these settings. 99mTc-RAFT-RGD is a novel 99mTc-labeled tracer that targets the αvβ3 integrin. Our objective was to determine whether this tracer was suitable for myocardial angiogenesis imaging. Methods and ResultsA rat model of reperfused myocardial infarction was employed. Fourteen days following reperfusion, the animals were injected with 99mTc-RAFT-RGD or with its negative control 99mTc-RAFT-RAD. Fourteen animals were dedicated to autoradiographic imaging, infarct staining, and gamma-well counting of myocardial activity. In vivo dual-isotope pinhole SPECT imaging of 201Tl and 99mTc-RAFT-RGD or 99mTc-RAFT-RAD was also performed in 11 additional animals. Neovessels were observed by immunostaining in the infarcted and peri-infarct areas. 99mTc-RAFT-RGD infarct-to-normal ratios by gamma-well counting and ex vivo imaging (2.5 ± 0.6 and 4.9 ± 0.9, respectively) were significantly higher than those of 99mTc-RAFT-RAD (1.7 ± 0.2 and 2.2 ± 0.4, respectively, P < .05). The infarcted area was readily visible in vivo by SPECT with 99mTc-RAFT-RGD but not with 99mTc-RAFT-RAD (infarct-to-normal zone activity ratio, 2.5 ± 0.6 and 1.7 ± 0.4, respectively, P < .05). Conclusion99mTc-RAFT-RGD allowed the experimental in vivo molecular imaging of myocardial angiogenesis.