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01-08-2018 | Original Article

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

Authors: Max Kiugel, BM, MSc, Ville Kytö, MD, PhD, Tiina Saanijoki, MSc, Heidi Liljenbäck, MSc, Olli Metsälä, BSc, Mia Ståhle, MSc, Johanna Tuomela, PhD, Xiang-Guo Li, PhD, Pekka Saukko, MD, PhD, Juhani Knuuti, MD, PhD, Anne Roivainen, PhD, Antti Saraste, MD, PhD

Published in: Journal of Nuclear Cardiology | Issue 4/2018

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.

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Title: Evaluation of 68Ga-labeled peptide tracer for detection of gelatinase expression after myocardial infarction in rat
Authors: Max Kiugel, BM, MSc
Ville Kytö, MD, PhD
Tiina Saanijoki, MSc
Heidi Liljenbäck, MSc
Olli Metsälä, BSc
Mia Ståhle, MSc
Johanna Tuomela, PhD
Xiang-Guo Li, PhD
Pekka Saukko, MD, PhD
Juhani Knuuti, MD, PhD
Anne Roivainen, PhD
Antti Saraste, MD, PhD
Publication date: 01-08-2018
Publisher: Springer US
Published in: Journal of Nuclear Cardiology / Issue 4/2018
Print ISSN: 1071-3581
Electronic ISSN: 1532-6551
DOI: https://doi.org/10.1007/s12350-016-0744-4

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

Abstract

Background

Methods

Results

Conclusions

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