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OtherBasic Science Investigations

99mTc-Annexin V Imaging for In Vivo Detection of Atherosclerotic Lesions in Porcine Coronary Arteries

Lynne L. Johnson, Lorraine Schofield, Tammy Donahay, Navneet Narula and Jagat Narula
Journal of Nuclear Medicine July 2005, 46 (7) 1186-1193;
Lynne L. Johnson
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Lorraine Schofield
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Tammy Donahay
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Navneet Narula
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Jagat Narula
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  • FIGURE 1.
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    FIGURE 1.

    (A) Example of scan-positive vessel, with in vivo SPECT reconstructions on left and phosphor screen images on right. RCA was injured vessel, and LCX was control vessel. Phosphor screen images show tracer uptake in proximal half of RCA specimen. Transverse, coronal, and sagittal reconstructions of in vivo images show linear uptake of tracer in region of RCA. In 3-dimensional image, upper threshold is turned down to bring out any focal uptake and exaggerate bone and liver activity. (B) Example of scan-negative vessel. Myocardial slices imaged on detector are on left and in vivo SPECT reconstructions on right. Scaling is similar to that in A. No focal uptake of tracer is seen in region of heart.

  • FIGURE 2.
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    FIGURE 2.

    SPECT reconstructions (left) and ex vivo–imaged myocardial slices (bottom right). This animal had LAD injury and apical infarct. Focal uptake is seen in LAD and apex of left ventricle. Myocardial uptake was confirmed on ex vivo images.

  • FIGURE 3.
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    FIGURE 3.

    Photomicrographs of sections of injured coronary artery. Neointimal thickening is seen, comprising predominantly spindle-shaped cells characteristic of class II lesions. Sections are stained with hematoxylin and eosin (H & E) (A), elastic stain (B), and trichrome (C). Vessel was flattened for phosphor screen. IEL = internal elastic membrane; L = lumen.

  • FIGURE 4.
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    FIGURE 4.

    Photomicrographs of serial sections from injured scan-positive coronary vessel stained for α-actin (A), caspase-3 (B), and macrophages (C). Lesion cells staining positively for caspase-3 (B) were determined to be smooth muscle cells on the basis of brown cytoplasmic staining (A) and negative staining for macrophages (C).

  • FIGURE 5.
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    FIGURE 5.

    Photomicrographs of sections stained for caspase-3 (brown nuclear stain) with blue nuclear counterstain. On left is section from scan-positive injured vessel; on right, section from scan-negative injured vessel.

  • FIGURE 6.
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    FIGURE 6.

    Animal injected with 99mTc-DTPA (control). SPECT reconstructions are on top, and photomicrograph of section from injured LAD is on bottom. No focal uptake of tracer is seen in region of heart. On immunohistochemical section, caspase chromagen is from a 3,3′-diaminobenzidine substrate kit (Vector Laboratories) and counterstain is nuclear fast red (Vector Laboratories). Section shows abundant brown nuclear and cytoplasmic staining corresponding to high rate of apoptosis in LAD.

  • FIGURE 7.
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    FIGURE 7.

    (A) Plot of count ratio (injured coronary artery to noninjured coronary artery) vs. apoptosis rate as determined from morphometric immunostaining. (B) Plot of tracer uptake vs. apoptosis rate. Closed circles represent experiments that did not show focal uptake in coronary arteries on in vivo SPECT; open circles represent experiments that did show focal uptake.

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    TABLE 1

    Results of Scanning and Immunohistochemistry

    Experiment no.VesselCount ratioApoptosis rate (%)In vivo scan interpretation
    2LAD2.660Positive
    RCA2.461Positive
    LCX controlTissue lostNegative
    3LADData lost68Positive
    RCA62Positive
    LCX controlTissue lostNegative
    4LAD256Positive
    RCA254Positive
    LCX control3Negative
    5LCX1.533Negative
    RCA1.130Negative
    LAD control6Negative
    6LCX1.320Negative
    RCA263Positive
    LAD control8Negative
    7LCX0.912Negative
    RCA1.516Negative
    LAD control6Negative
    8RCA2.568Positive
    LCX control15Negative
    LAD not injected9Negative
    9LCX1.552.5Negative
    RCA480Positive
    LAD2.7Tissue lostPositive
    Distal LAD control0.7Negative
    10LCX2.160Positive
    RCA1.26Negative
    LAD control2.4Negative
    11LAD1.416Negative
    LCX11Negative
    RCA control1.3Negative
    12RCA250Positive
    LCX1.956Positive
    LAD control2Negative
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Journal of Nuclear Medicine: 46 (7)
Journal of Nuclear Medicine
Vol. 46, Issue 7
July 1, 2005
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99mTc-Annexin V Imaging for In Vivo Detection of Atherosclerotic Lesions in Porcine Coronary Arteries
Lynne L. Johnson, Lorraine Schofield, Tammy Donahay, Navneet Narula, Jagat Narula
Journal of Nuclear Medicine Jul 2005, 46 (7) 1186-1193;

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99mTc-Annexin V Imaging for In Vivo Detection of Atherosclerotic Lesions in Porcine Coronary Arteries
Lynne L. Johnson, Lorraine Schofield, Tammy Donahay, Navneet Narula, Jagat Narula
Journal of Nuclear Medicine Jul 2005, 46 (7) 1186-1193;
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  • Imaging Atherosclerosis and Vulnerable Plaque
  • Molecular Imaging of Macrophage Cell Death for the Assessment of Plaque Vulnerability
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  • Targeting of Lectinlike Oxidized Low-Density Lipoprotein Receptor 1 (LOX-1) with 99mTc-Labeled Anti-LOX-1 Antibody: Potential Agent for Imaging of Vulnerable Plaque
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  • Broad and Specific Caspase Inhibitor-Induced Acute Repression of Apoptosis in Atherosclerotic Lesions Evaluated by Radiolabeled Annexin A5 Imaging
  • Application of 18F-FDG PET for Monitoring the Therapeutic Effect of Antiinflammatory Drugs on Stabilization of Vulnerable Atherosclerotic Plaques
  • New Opportunities for Identification and Reduction of Coronary Risk: Treatment of Vulnerable Patients, Arteries, and Plaques
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