Evaluation of 68Ga-labeled peptide tracer for detection of gelatinase expression after myocardial infarction in rat.

Abstract

BACKGROUND:

Matrix metalloproteinases 2 and 9 (MMP-2/9) play a role in extracellular matrix remodeling after an ischemic myocardial injury. We evaluated 68Ga-DOTA-peptide targeting MMP-2/9 for the detection of gelatinase expression after myocardial infarction (MI) in rat.

METHODS:

Rats were injected with 43 ± 7.7 MBq of 68Ga-DOTA-peptide targeting MMP-2/9 at 7 days (n = 7) or 4 weeks (n = 8) after permanent coronary ligation or sham operation (n = 5 at both time points) followed by positron emission tomography (PET). The left ventricle was cut in frozen sections for autoradiography and immunohistochemistry 30 minutes after tracer injection.

RESULTS:

Immunohistochemical staining showed MMP-2 and MMP-9 expressing cells, CD31-positive endothelial cells, and CD68-positive macrophages in the infarcted myocardium. Autoradiography showed increased tracer uptake in the infarcted area both at 7 days and 4 weeks after MI (MI-to-remote area ratio 2.5 ± 0.46 and 3.1 ± 1.0, respectively). Tracer uptake in damaged tissue correlated with the amount of CD68-positive macrophages at 7 days after MI, and CD31-positive endothelial cells at 7 days and 4 weeks after MI. The tracer was rapidly metabolized, radioactivity in the blood exceeded that of the myocardium, and tracer accumulation in the heart was not detectable by in vivo PET.

CONCLUSIONS:

68Ga-DOTA-peptide targeting MMP-2/9 accumulates in the damaged rat myocardium after an ischemic injury, but tracer instability and slow clearance in vivo make it unsuitable for further evaluation.

• Authors: Max Kiugel, Ville Kytö, Tiina Saanijoki, Heidi Liljenbäck, Olli Metsälä, Mia Ståhle, Johanna Tuomela, Xiang-Guo Li, Pekka Saukko, Juhani Knuuti, Anne Roivainen, Antti Saraste
• Journal: Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology (J Nucl Cardiol) Vol. 25 Issue 4 Pg. 1114-1123 (08 2018) ISSN: 1532-6551 [Electronic] United States
• PMID: 27914007 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Gallium Radioisotopes
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Animals
• Autoradiography
• Gallium Radioisotopes
• Male
• Matrix Metalloproteinase 2 (analysis)
• Matrix Metalloproteinase 9 (analysis)
• Myocardial Infarction (enzymology)
• Myocardium (enzymology)
• Positron-Emission Tomography
• Rats
• Rats, Sprague-Dawley