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Journal of Nuclear Medicine

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OtherBasic Science Investigations

Pharmacokinetics and Biodistribution of 86Y-Trastuzumab for 90Y Dosimetry in an Ovarian Carcinoma Model: Correlative MicroPET and MRI

Stig Palm, Richard M. Enmon, Cornelia Matei, Katherine S. Kolbert, Su Xu, Pat B. Zanzonico, Ronald L. Finn, Jason A. Koutcher, Steven M. Larson and George Sgouros
Journal of Nuclear Medicine July 2003, 44 (7) 1148-1155;
Stig Palm
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Richard M. Enmon Jr.
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Cornelia Matei
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Katherine S. Kolbert
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Su Xu
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Pat B. Zanzonico
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Ronald L. Finn
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Jason A. Koutcher
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Steven M. Larson
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George Sgouros
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  • FIGURE 1.
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    FIGURE 1.

    Dissected mouse. Arrow indicates location of small tumor nodules on spleen.

  • FIGURE 2.
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    FIGURE 2.

    Longitudinal microPET coronal slice images of 86Y-trastuzumab (A), excess unlabeled trastuzumab (B), 86Y-trastuzumab on nontumor-bearing mice (C), 86Y-HuM195 (D), and free 86Y (E). Numbers in upper left corner of each panel indicate time after injection (in hours). Black arrows indicate mAb accumulation at confirmed tumor sites. White arrows indicate injection site.

  • FIGURE 3.
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    FIGURE 3.

    (A) High-resolution transverse MR image slices, registered to corresponding microPET slices. Contours depicting outer periphery of mouse and also collection of tumor nodules near spleen are shown. (B) Two transverse MR slices, obtained on small-animal (4.7 T) scanner, are shown. Two slices are taken at different transaxial positions. Slice on left is through spleen (yellow contour), kidneys (blue), and tumor nodules (orange). Slice on right is posterior to left slice and depicts multiple small tumor nodules in mesentery.

  • FIGURE 4.
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    FIGURE 4.

    (A) Time–activity curve over injection site. Relative activity concentrations were determined by drawing ROIs on microPET image sets. Data are corrected for acquisition time, physical decay, and background. Error bars represent SE. (B) Time–activity curves for blood (triangles) and tumor (squares). Open symbols represent relative activity concentration (e.g., pharmacokinetics) derived from repeated microPET imaging. Activity concentrations (%IA/g) in dissected tissue (solid symbols) were used to quantitate image-based relative concentrations. Error bars represent combined standard uncertainty. Lines show fits used for cumulated activity calculations.

  • FIGURE 5.
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    FIGURE 5.

    Uptake in various tissues 6 d after intraperitoneal injection with 86Y-trastuzumab (86Y-Herceptin), excess unlabeled (cold) trastuzumab, and 86Y-HuM195. Mean values and SE are shown.

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    TABLE 1

    Absorbed Doses to Organs and Tumors of Varying Sizes After Intraperitoneal Injection of 90Y-Trastuzumab

    Organ or tumorRadius (mm)Absorbed fractionDose (Gy/MBq)
    Tumor0.10.0170.10
    Tumor0.50.0840.48
    Tumor1.00.170.96
    Tumor3.00.452.6
    Tumor5.00.633.7
    Liver0.690.48
    Kidneys0.520.31
    Spleen0.340.56
    • Calculation based on pharmacokinetics and biodistribution of intraperitoneally injected 86Y-trastuzumab.

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Journal of Nuclear Medicine
Vol. 44, Issue 7
July 1, 2003
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Pharmacokinetics and Biodistribution of 86Y-Trastuzumab for 90Y Dosimetry in an Ovarian Carcinoma Model: Correlative MicroPET and MRI
Stig Palm, Richard M. Enmon, Cornelia Matei, Katherine S. Kolbert, Su Xu, Pat B. Zanzonico, Ronald L. Finn, Jason A. Koutcher, Steven M. Larson, George Sgouros
Journal of Nuclear Medicine Jul 2003, 44 (7) 1148-1155;

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Pharmacokinetics and Biodistribution of 86Y-Trastuzumab for 90Y Dosimetry in an Ovarian Carcinoma Model: Correlative MicroPET and MRI
Stig Palm, Richard M. Enmon, Cornelia Matei, Katherine S. Kolbert, Su Xu, Pat B. Zanzonico, Ronald L. Finn, Jason A. Koutcher, Steven M. Larson, George Sgouros
Journal of Nuclear Medicine Jul 2003, 44 (7) 1148-1155;
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