Research ArticleSPECIAL CONTRIBUTION

MIRD Pamphlet No. 31: MIRDcell V4—Artificial Intelligence Tools to Formulate Optimized Radiopharmaceutical Cocktails for Therapy

Sumudu Katugampola, Jianchao Wang and Roger W. Howell
Journal of Nuclear Medicine December 2024, 65 (12) 1965-1973; DOI: https://doi.org/10.2967/jnumed.123.267238

Article Figures & Data

Figures

  • Figure
  • FIGURE 1.
    FIGURE 1.

    Nonuniform distribution of radiopharmaceuticals (drugs) among cells.

  • FIGURE 2.
    FIGURE 2.

    Total disintegrations required to achieve target SF of 0.0001 for each drug combination. Bar for Ab4 (2.66 × 109 Bq) has been cut off to provide this zoomed-in version focusing on disintegrations up to ∼5 × 108 Bq.

  • FIGURE 3.
    FIGURE 3.

    Total number of disintegrations required to achieve target SF of 0.001 for each combination of 2 195mPt-radiopharmaceuticals that are independently distributed lognormally among cells comprising spheric multicellular cluster with radius of 200 μm. Details regarding parameter settings are provided in Supplemental Figure 4.

  • FIGURE 4.
    FIGURE 4.

    Total disintegrations of 225Ac required to achieve target SF of 0.001 in multicellular cluster with radius of 190 μm for each possible combination of 2 225Ac-labeled drugs. Drug 1 is 225Ac-liposomes; drug 2 is exponential radial distribution of 225Ac with penetration depth of 30 μm. In this zoomed-in version, blue bar for drug 2 alone extends beyond top of figure. Drug 1 has 46,640 decays; drug 2 has 68,390,000 decays; drug 1 (17,844) with drug 2 (6,668) has 24,451 decays. 1 decay = 1 Bq s.

  • FIGURE 5.
    FIGURE 5.

    (A) Radial distribution of absorbed doses to cells within spheroid from optimized cocktail of 225Ac-liposomes (drug 1, magenta) and 225Ac-labeled drug with exponential radial distribution (drug 2, blue). (B) Dose–volume histogram resulting from optimization of 2 drugs. As per Figure 4, total decay is 24,451 Bq.

Tables

  • TABLE 1.

    Optimized Results for Each Combination of 211At-Labeled Abs

    Drug combinationTotal disintegrations required*Molar activity required (GBq/mol)*
    Ab14.3 × 1081.6 × 108
    Ab24.5 × 1081.5 × 107
    Ab33.7 × 1084.8 × 107
    Ab42.7 × 1086.7 × 107
    Ab1 + Ab24.3 × 1081.6 × 106, 1.4 × 107
    Ab2 + Ab32.3 × 1084.2 × 106, 1.4 × 107
    Ab3 + Ab42.7 × 1081.7 × 107, 3.4 × 106
    Ab1 + Ab33.7 × 1085.7 × 104, 4.8 × 107
    Ab2 + Ab43.7 × 1081.2 × 107, 2.0 × 10–7
    Ab1 + Ab43.1 × 1085.9 × 107, 3.9 × 106
    Ab1 + Ab2 + Ab32.3 × 1080, 4.0 × 106, 1.4 × 107
    Ab1 + Ab3 + Ab42.3 × 1086.0 × 107, 2.6 × 106, 1.3 × 106
    Ab1 + Ab2 + Ab42.3 × 1085.3 × 107, 3.0 × 106, 9.0 × 103
    Ab2 + Ab3 + Ab42.3 × 1084.1 × 106, 1.4 × 107, 2.5 × 104
    Ab1 + Ab2 + Ab3 + Ab42.0 × 1084.0 × 107, 2.1 × 106, 3.8 × 106, 0

    • * Rounded to 2 significant figures.

  • TABLE 2.

    Optimized Results for Each 195mPt–Drug Combination

    Drug combinationTotal disintegrations requiredMolar activity required (GBq/mol)
    Drug 11.7 × 1076.1 × 106
    Drug 21.7 × 1076.0 × 106
    Drug 1 + Drug 21.0 × 1071.8 × 106, 1.9 × 106

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