Research ArticleTheranostics

Model of Intraperitoneal Targeted α-Particle Therapy Shows That Posttherapy Cold-Antibody Boost Enhances Microtumor Radiation Dose and Treatable Tumor Sizes

Stig Palm, Tom Bäck, Sture Lindegren, Ragnar Hultborn, Lars Jacobsson and Per Albertsson
Journal of Nuclear Medicine April 2018, 59 (4) 646-651; DOI: https://doi.org/10.2967/jnumed.117.201285

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Simulated penetration of mAbs in microtumor after intraperitoneal infusion of radiolabeled mAb. Concentration of mAb is shown at different depths in microtumors at various times after intraperitoneal infusion of 300 MBq of 211At-mAb of relatively high specific activity (1 in 200 mAbs radiolabeled) and low specific activity (1 of 30,000 mAbs radiolabeled). Concentration is normalized to that of complete saturation—that is, when all antigens in that shell are occupied by a mAb.

  • FIGURE 2.
    FIGURE 2.

    Absorbed doses at various depths of 400-μm-radius microtumor after intraperitoneal infusion of 300 MBq of 211At-mAb of relatively high specific activity (1 of 200 mAbs radiolabeled) and low specific activity (1 of 30,000 mAbs radiolabeled).

  • FIGURE 3.
    FIGURE 3.

    Absorbed dose distribution for microtumors with radii of 400, 200, and 100 μm. Each graph is illustrated by mid-sphere section, with gray-scale–coded shells representing likely eradicative absorbed doses (>10 Gy, black), likely insufficient absorbed doses (<1 Gy, white), and absorbed doses for which biologic outcome is less certain (gray).

  • FIGURE 4.
    FIGURE 4.

    Absorbed dose distribution to spheric tumors with radii of 100, 200, 300, and 400 μm after intraperitoneal infusion of high-specific-activity 211At-mAb (1 in 200 mAbs radiolabeled) followed by boost with 150 times mAb amount of first infusion. Shown are results when posttherapy cold-antibody boost is delivered 1 h after therapy (top) and 5 h after therapy (bottom). Dashed line shows results without posttherapy cold-antibody boost.

Tables

  • TABLE 1

    Description of Parameters used in Equations 1 and 2

    ParameterDescription
    ViShell volume
    AiIntersection area between shells
    ni(t)Number of free mAbs in shell i
    Ci(t)Antibody concentration in shell i
    nag,i(t)Number of free antigens in shell i
    ∆ni(t)Number of transferred mAbs
    nbi(t)Number of bound mAbs in shell i
  • TABLE 2

    Parameter Values Used for the Presented Simulations

    ParameterValue
    Administered activity300 MBq of 211At
    Administered fluid1.7 L of icodextrin
    Fraction of labeled mAbs1 in 200 mAbs radiolabeled
    D14 μm2s−1 (21)
    f (fraction fluid in tumor)0.1 (11) (cell-packing ratio, 1 − f)
    ∆t0.5 s
    ∆x5 or 10 μm
    kon44,000 M−1s−1 (4)
    koff0
    Antigens per cell700,000 (4)

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