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Research ArticleBasic Science Investigations

The Intratumoral Distribution of Radiolabeled 177Lu-BR96 Monoclonal Antibodies Changes in Relation to Tumor Histology over Time in a Syngeneic Rat Colon Carcinoma Model

Anders Örbom, Sophie E. Eriksson, Erika Elgström, Tomas Ohlsson, Rune Nilsson, Jan Tennvall and Sven-Erik Strand
Journal of Nuclear Medicine August 2013, 54 (8) 1404-1410; DOI: https://doi.org/10.2967/jnumed.112.117028
Anders Örbom
1Department of Medical Radiation Physics, Lund University, Lund, Sweden
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Sophie E. Eriksson
2Department of Oncology, Lund University, Lund, Sweden; and
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Erika Elgström
2Department of Oncology, Lund University, Lund, Sweden; and
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Tomas Ohlsson
1Department of Medical Radiation Physics, Lund University, Lund, Sweden
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Rune Nilsson
2Department of Oncology, Lund University, Lund, Sweden; and
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Jan Tennvall
2Department of Oncology, Lund University, Lund, Sweden; and
3Department of Oncology, Skåne University Hospital, Lund, Sweden
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Sven-Erik Strand
1Department of Medical Radiation Physics, Lund University, Lund, Sweden
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  • FIGURE 1.
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    FIGURE 1.

    Representative tumor sections from group 2 at 4 time points after injection. From left to right: digital autoradiography images of 177Lu distribution scaled to %IA/g, adjacent sections stained with hematoxylin and eosin for histologic examination, adjacent sections stained with BR96 antibody to determine antigen distribution, and absorbed-dose rate distribution at time of sacrifice based on activity image (individually scaled). ROIs used in correlation analysis are outlined in red where applicable. Sections from group 2 are displayed due to visually better-quality staining for antigen distribution. Peripheral distribution of activity in each nodule is shown at 8 h after injection (A), and correlation between uptake and antigen is shown at 24 h after injection (B). At 48 h after injection (C), this correlation has given way to correlation between activity and antigen-negative granulation tissue, which is even more pronounced at 120 h after injection (D). p.i. = after injection.

  • FIGURE 2.
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    FIGURE 2.

    Representative tumor sections from untreated animals (top), and animals treated with 1.0 mg/kg dose of unlabeled mAb 48 h after injection (bottom). Sections are stained with hematoxylin and eosin (A and C) and BR96 antibody (B and D). Reduction in viable, antigen-expressing tumor cells is seen in tumor treated with unlabeled mAb.

  • FIGURE 3.
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    FIGURE 3.

    Scatter plots demonstrating changing correlation between antigen expression and activity over time. p.i. = after injection.

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    TABLE 1

    Experimental Details for Two Animal Groups

    No. of animals sacrificed at each time point after injection
    GroupInjected activity (MBq/kg)2 h8 h24 h48 h72 h96 h120 h168 h
    1503323—33—
    225—3333333
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    TABLE 2

    Activity of 177Lu-DOTA-BR96 in Tumor and Blood

    177Lu-DOTA-BR96 activity (%IA/g)
    Time after injection (h)TumorBlood
    0—6.72 (5.82–8.70)
    21.97 (1.54–2.13)—
    84.37 (3.15–6.38)4.29 (4.13–4.62)
    246.95 (5.09–10.2)2.81 (2.52–2.94)
    488.43 (6.34–9.81)2.12 (1.95–2.43)
    7214.9 (7.48–19.0)1.81 (1.37–1.99)
    9610.6 (4.24–20.7)1.45 (1.29–1.89)
    1207.80 (2.65–13.0)1.56 (1.45–1.64)
    16828.3 (11.6–52.1)1.17 (0.98–1.69)
    • Data are median, followed by range in parentheses.

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    TABLE 3

    Estimated Absorbed-Dose Rates for Whole Tumor Sections and High- and Low-Uptake Regions (Relative to Each Section)

    Mean absorbed-dose (mGy/min)
    Whole tumor sectionsHigh-uptake ROIsLow-uptake ROIs
    Time after injection (h)Group 1Group 2Group 1Group 2Group 1Group 2
    20.10 (0.10–0.20)—0.40 (0.30–0.50)—0.10 (0.00–0.10)—
    80.37 (0.27–0.43)0.49 (0.40–0.52)0.67 (0.61–1.13)1.01 (0.70–1.31)0.18 (0.15–0.30)0.27 (0.15–0.37)
    24(0.54–0.79)0.48 (0.33–0.58)1.12 (1.09–1.81)0.81 (0.59–1.08)0.47 (0.14–0.51)0.25 (0.17–0.52)
    480.60 (0.49–0.65)0.53 (0.46–0.60)1.06 (0.78–1.35)0.90 (0.56–1.15)0.33 (0.21–0.67)0.28 (0.22–0.51)
    72—0.71 (0.29–0.84)—1.43 (0.51–1.65)—0.27 (0.17–0.77)
    960.43 (0.25–1.04)0.39 (0.38–0.63)0.78 (0.48–1.03)0.93 (0.70–1.17)0.23 (0.18–0.35)0.35 (0.19–0.53)
    1200.38 (0.30–0.66)0.37 (0.34–1.88)0.78 (0.56–1.43)0.79 (0.45–3.62)0.23 (0.17–0.34)0.29 (0.17–2.92)
    168—1.10 (0.76–2.40)—1.73 (1.23–5.31)—0.52 (0.17–3.01)
    • Data are median, followed by range in parentheses.

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    TABLE 4

    Correlation Between Activity Uptake and Absorbed-Dose Rate at Time of Sacrifice vs. Antigen-Positive Area Fraction in ROIs of Tumor Sections

    Pearson correlation coefficient
    Time after injection(h)Antigen vs. activity uptakeAntigen vs. absorbed-dose rate at time of sacrifice
    80.450*0.568†
    240.384*0.405*
    48−0.432*−0.490*
    96−0.711†−0.643†
    120−0.621†−0.572†
    • ↵* P < 0.05.

    • ↵† P < 0.001.

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Journal of Nuclear Medicine: 54 (8)
Journal of Nuclear Medicine
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August 1, 2013
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The Intratumoral Distribution of Radiolabeled 177Lu-BR96 Monoclonal Antibodies Changes in Relation to Tumor Histology over Time in a Syngeneic Rat Colon Carcinoma Model
Anders Örbom, Sophie E. Eriksson, Erika Elgström, Tomas Ohlsson, Rune Nilsson, Jan Tennvall, Sven-Erik Strand
Journal of Nuclear Medicine Aug 2013, 54 (8) 1404-1410; DOI: 10.2967/jnumed.112.117028

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The Intratumoral Distribution of Radiolabeled 177Lu-BR96 Monoclonal Antibodies Changes in Relation to Tumor Histology over Time in a Syngeneic Rat Colon Carcinoma Model
Anders Örbom, Sophie E. Eriksson, Erika Elgström, Tomas Ohlsson, Rune Nilsson, Jan Tennvall, Sven-Erik Strand
Journal of Nuclear Medicine Aug 2013, 54 (8) 1404-1410; DOI: 10.2967/jnumed.112.117028
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Keywords

  • radioimmunotherapy
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