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

Myocardial 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. Tc-99m-RAFT-RGD is a novel Tc-99m-labeled tracer that targets the alpha(v)beta(3) integrin. Our objective was to determine whether this tracer was suitable for myocardial angiogenesis imaging. A rat model of reperfused myocardial infarction was employed. Fourteen days following reperfusion, the animals were injected with Tc-99m-RAFT-RGD or with its negative control Tc-99m-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 Tl-201 and Tc-99m-RAFT-RGD or Tc-99m-RAFT-RAD was also performed in 11 additional animals. Neovessels were observed by immunostaining in the infarcted and peri-infarct areas. Tc-99m-RAFT-RGD infarct-to-normal ratios by gamma-well counting and ex vivo imaging (2.5 +/- A 0.6 and 4.9 +/- A 0.9, respectively) were significantly higher than those of Tc-99m-RAFT-RAD (1.7 +/- A 0.2 and 2.2 +/- A 0.4, respectively, P < .05). The infarcted area was readily visible in vivo by SPECT with Tc-99m-RAFT-RGD but not with Tc-99m-RAFT-RAD (infarct-to-normal zone activity ratio, 2.5 +/- A 0.6 and 1.7 +/- A 0.4, respectively, P < .05). Tc-99m-RAFT-RGD allowed the experimental in vivo molecular imaging of myocardial angiogenesis.