In vivo molecular imaging of myocardial angiogenesis using the alpha(v)beta3 integrin-targeted tracer 99mTc-RAFT-RGD

J Nucl Cardiol. 2010 Jun;17(3):435-43. doi: 10.1007/s12350-010-9191-9. Epub 2010 Jan 20.

Abstract

Background: 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. (99m)Tc-RAFT-RGD is a novel (99m)Tc-labeled tracer that targets the alpha(v)beta(3) integrin. Our objective was to determine whether this tracer was suitable for myocardial angiogenesis imaging.

Methods and results: A rat model of reperfused myocardial infarction was employed. Fourteen days following reperfusion, the animals were injected with (99m)Tc-RAFT-RGD or with its negative control (99m)Tc-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 (201)Tl and (99m)Tc-RAFT-RGD or (99m)Tc-RAFT-RAD was also performed in 11 additional animals. Neovessels were observed by immunostaining in the infarcted and peri-infarct areas. (99m)Tc-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 (99m)Tc-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 (99m)Tc-RAFT-RGD but not with (99m)Tc-RAFT-RAD (infarct-to-normal zone activity ratio, 2.5 +/- 0.6 and 1.7 +/- 0.4, respectively, P < .05).

Conclusion: (99m)Tc-RAFT-RGD allowed the experimental in vivo molecular imaging of myocardial angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • Cells, Cultured
  • Immunohistochemistry
  • Integrin alphaVbeta3 / metabolism*
  • Iodine Radioisotopes
  • Male
  • Myocardial Reperfusion Injury / diagnostic imaging*
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / physiopathology
  • Neovascularization, Physiologic*
  • Organotechnetium Compounds*
  • Peptides, Cyclic*
  • Radionuclide Imaging
  • Radiopharmaceuticals*
  • Rats
  • Rats, Wistar
  • Tissue Distribution

Substances

  • Integrin alphaVbeta3
  • Iodine Radioisotopes
  • Organotechnetium Compounds
  • Peptides, Cyclic
  • Radiopharmaceuticals
  • technetium 99m RAFT-RGD