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Research ArticleBasic Science Investigations

Radiolabeled Fucoidan as a P-Selectin Targeting Agent for In Vivo Imaging of Platelet-Rich Thrombus and Endothelial Activation

François Rouzet, Laure Bachelet-Violette, Jean-Marc Alsac, Michimasa Suzuki, Alain Meulemans, Liliane Louedec, Anne Petiet, Martine Jandrot-Perrus, Frédéric Chaubet, Jean-Baptiste Michel, Dominique Le Guludec and Didier Letourneur
Journal of Nuclear Medicine September 2011, 52 (9) 1433-1440; DOI: https://doi.org/10.2967/jnumed.110.085852
François Rouzet
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Laure Bachelet-Violette
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Jean-Marc Alsac
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Michimasa Suzuki
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Alain Meulemans
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Liliane Louedec
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Anne Petiet
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Martine Jandrot-Perrus
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Frédéric Chaubet
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Jean-Baptiste Michel
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Dominique Le Guludec
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Didier Letourneur
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  • FIGURE 1.
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    FIGURE 1.

    Blood clearance of 99mTc-fucoidan. After correction for residual activity in injection site and decay, results are expressed as percentage of administered dose remaining in blood pool according to time, assuming that blood represents 6% of body weight.

  • FIGURE 2.
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    FIGURE 2.

    Aortic valve endocarditis in rat. Coronal and sagittal slices on SPECT/CT coregistration are shown, with an example of focal 99mTc-fucoidan uptake (red cross) in aortic valve area. Additional uptake is seen in spine and upper extremities of humeral bones.

  • FIGURE 3.
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    FIGURE 3.

    Aortic valve endocarditis in rat. Comparison of histology (5-μm thickness, Alcian blue staining), autoradiography, and P-selectin immunostaining (with nuclear counterstaining) in same vegetation (adjacent slices for histology and autoradiography but not for immunostaining). Two vegetations are present on this sample: one attached to aorta wall damaged by catheter path (solid arrow) and second attached to aortic valve (dotted arrow). There is clear colocalization of 99mTc-fucoidan uptake and immunostaining on both vegetations but not within damaged myocardium underlying vegetation (proteoglycans are stained in blue, indicated by arrowheads).

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    FIGURE 4.

    Intraluminal thrombus in AAA in rat. Compared analysis of histology (Masson trichrome) and autoradiography on same slice (cryostat section, 20-μm thickness; Masson trichrome staining has been performed after autoradiographic acquisition) and P-selectin immunostaining with nuclear counterstaining (different sample). Mural thrombus on Masson trichrome staining (arrows) matched 99mTc-fucoidan uptake on autoradiography. P-selectin positivity on immunostaining was localized within thrombus, which is spreading at surface of aneurysm wall.

  • FIGURE 5.
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    FIGURE 5.

    Ischemia–reperfusion after transient occlusion of left anterior descending coronary artery in rat. (A) SPECT/CT acquired after 2 h of reperfusion shows high 99mTc-fucoidan uptake in anterior wall (arrow). 99mTc-fucoidan uptake on SPECT is quantified on short-axis slices as ratio between activity of region of interest drawn around focal ventricular uptake (line) and background activity (white dotted circle over right ventricular blood pool). (B) Autoradiography of axial slice of midventricular portion of heart: uptake in area at risk matched P-selectin immunostaining (peroxidase/3,3-diaminobenzidine; magnification, ×40) on vessels wall. Conversely, no significant radiotracer uptake or immunostaining was detected in remote myocardium. (C) At left is cross-sectional extent of injured myocardium quantified on autoradiographic slice perpendicular to long axis of heart taken in midventricular segment, as percentage of surface of area with increased radioactivity (red line) to total surface of left ventricle (blue line). At right is correlation between 99mTc-fucoidan uptake on SPECT and cross-sectional extent of injured myocardium on autoradiography (Y = 2.223 + 9.681 × X; R = 0.7; P = 0.04).

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    TABLE 1

    Biodistribution of 99mTc-Fucoidan in Rats (n = 4) 2 Hours After Intravenous Injection

    OrganPercentage of administered dose per gram of tissuePercentage of administered dose per organ
    Blood0.624 ± 0.04211.73 ± 0.79
    Kidneys4.801 ± 0.68112.17 ± 1.49
    Urine*34.171 ± 11.9518.07 ± 5.54
    Liver0.619 ± 0.0827.85 ± 1.10
    Spleen0.213 ± 0.0550.182 ± 0.029
    Bones0.559 ± 0.09316.58 ± 2.73
    Muscle0.040 ± 0.0125.02 ± 1.53
    Skin0.164 ± 0.0759.20 ± 4.16
    Heart0.110 ± 0.0090.129 ± 0.027
    Lungs0.172 ± 0.0280.270 ± 0.047
    Thyroid0.250 ± 0.1000.005 ± 0.002
    Brain0.014 ± 0.0020.019 ± 0.001
    • * Because there was no urination during study, this is cumulative activity of first 2 h after injection.

    • Results are expressed as mean ± SD.

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Journal of Nuclear Medicine: 52 (9)
Journal of Nuclear Medicine
Vol. 52, Issue 9
September 1, 2011
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Radiolabeled Fucoidan as a P-Selectin Targeting Agent for In Vivo Imaging of Platelet-Rich Thrombus and Endothelial Activation
François Rouzet, Laure Bachelet-Violette, Jean-Marc Alsac, Michimasa Suzuki, Alain Meulemans, Liliane Louedec, Anne Petiet, Martine Jandrot-Perrus, Frédéric Chaubet, Jean-Baptiste Michel, Dominique Le Guludec, Didier Letourneur
Journal of Nuclear Medicine Sep 2011, 52 (9) 1433-1440; DOI: 10.2967/jnumed.110.085852

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Radiolabeled Fucoidan as a P-Selectin Targeting Agent for In Vivo Imaging of Platelet-Rich Thrombus and Endothelial Activation
François Rouzet, Laure Bachelet-Violette, Jean-Marc Alsac, Michimasa Suzuki, Alain Meulemans, Liliane Louedec, Anne Petiet, Martine Jandrot-Perrus, Frédéric Chaubet, Jean-Baptiste Michel, Dominique Le Guludec, Didier Letourneur
Journal of Nuclear Medicine Sep 2011, 52 (9) 1433-1440; DOI: 10.2967/jnumed.110.085852
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