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


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).


CONCLUSIONS
(99m)Tc-RAFT-RGD allowed the experimental in vivo molecular imaging of myocardial angiogenesis.
Dimastromatteo
Julien
J
INSERM U877, Radiopharmaceutiques Biocliniques, Faculté de Médecine de Grenoble, 38700 La Tronche, Grenoble, France.
Riou
Laurent M
LM
Ahmadi
Mitra
M
Pons
Guillaume
G
Pellegrini
Eric
E
Broisat
Alexis
A
Sancey
Lucie
L
Gavrilina
Tatiana
T
Boturyn
Didier
D
Dumy
Pascal
P
Fagret
Daniel
D
Ghezzi
Catherine
C
D000818:Animals; D001345:Autoradiography; D002478:Cells, Cultured; D007150:Immunohistochemistry; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology; D018919:Neovascularization, Physiologic; D015609:Organotechnetium Compounds; D010456:Peptides, Cyclic; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D039302:Integrin alphaVbeta3; D007457:Iodine Radioisotopes; D015609:Organotechnetium Compounds; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; C529229:technetium 99m RAFT-RGD