量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果(学会誌発表論文、学会発表、研究開発報告書、特許等)を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum and Radiological Science and Technology.
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Background: During tissue remodeling after acute myocardial infarction (MI), tenascin-C (TNC), one of extracellular matrix glycoproteins, loosens the strong adhesion of surviving cardiomyocytes at the border zone to reorganize the cell shape or arrangement. To develop a new noninvasive diagnostic technique for the early tissue remodeling after acute MI, we tried to detect active region of tissue remodeling using radiolabeled anti-TNC antibody and single-photon emission computed tomography (SPECT). Methods: 125I anti-TNC monoclonal antibody fragment was injected intravenously to 5 acute MI rats (D) at 5 days after operation, and 5 sham-operated rats (C), and the biodistribution of this radiotracer was measured. Excised and sectioned hearts were stained with hematoxylin and eosin for histological analysis and were exposed to autoradiography. Dual-isotope SPECT imaging of 111In anti-TNC antibody and 99mTc-MIBI was also performed to examine the feasibility of this tracer for in vivo imaging. Results: Average whole heart myocardial radioactivity was significantly higher in D than C (D, 0.19+/-0.02 %injected-dose/g; C, 0.12+/-0.00; p < 0.01). Myocardial radioactivity in the infarcted area was also significantly higher in D than C (D, 0.20+/-0.02 %injected-dose/g; C, 0.11+/-0.01, p < 0.01) By autoradiography, high radioactivities were observed in the periphery of the necrotic mass in the granulation tissue. D-to-C ratio of the average autoradiographic intensity of myocardial tissue was 1.56. The ratio of autoradiographic intensities of infarcted area to noninfarcted area was 1.77. SPECT imaging demonstrated the regional myocardial uptake of 111In anti-TNC antibody, which was complementary to perfusion image. In addition, tracer distribution in the infarcted area was relatively heterogeneous. Conclusions: The present study indicated a high ability of the radiolabeled anti-TNC fragments to localize the infarcted region in the heart by ex-vivo and in-vivo imagings, suggesting its potential usefulness for the noninvasive detection of tissue remodeling.