Research ArticleClinical Investigations

A Microdosimetric Analysis of Absorbed Dose to Tumor as a Function of Number of Microspheres per Unit Volume in 90Y Radioembolization

Alexander S. Pasciak, Austin C. Bourgeois and Yong C. Bradley
Journal of Nuclear Medicine July 2016, 57 (7) 1020-1026; DOI: https://doi.org/10.2967/jnumed.115.163444

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Simplified flowchart describing algorithm used to identify microsphere cluster locations and size. C = microsphere cluster; D = sampled distance between microsphere clusters; S = cluster size; ||x|| = vector norm operator; XYZ = vector describing spatial coordinates of cluster center.

  • FIGURE 2.
    FIGURE 2.

    Microscopic deposition of spheres at number density of 50,000 spheres/mL. Small clusters (white arrow) and large clusters (black arrow) are apparent. Monte Carlo process allows for realistic microscopic distribution consistent with experimental findings, including oblique clusters. For comparison, expanded section shows microscopic view of oblique cluster of resin microspheres surrounding arteriole in animal tissue.

  • FIGURE 3.
    FIGURE 3.

    Results of simulations using uniform approach in which Davg is average absorbed dose to tissue volume. (A) D70, D90, and D95 as function of average microsphere-number density. Error bars show SD from 20 independent simulations. (B) Specific-microsphere-activity (As) horizontal axis labels for A with average absorbed doses of 100 and 250 Gy, as computed using Equation 2. (C) Fraction of microscopic clusters populated by at least 1 microsphere as function of average microsphere-number density (D) Dose–volume histograms for microsphere-number densities of 200, 1,000, 10,000, and 50,000 spheres/mL. For clarity, error bars are shown on 200 spheres/mL curve only.

  • FIGURE 4.
    FIGURE 4.

    (A) 90Y PET/CT of left-lobe tumor reveals peripheral deposition of microspheres. (B) Corresponding microdosimetric absorbed-dose heat map of 100-μm slice after population of tumor volume with average number density of 10,000 spheres/mL.

  • FIGURE 5.
    FIGURE 5.

    D70 as function of microsphere-number density for all tumors in Table 2, where Davg is average absorbed dose to tumor volume. Error bars have been omitted for clarity. Shaded area represents number densities that result in statistically significant differences with D70 at 50,000 spheres/mL. Average absorbed dose, microsphere-number density, and specific activity per sphere are related in Equation 2.

  • FIGURE 6.
    FIGURE 6.

    Dose–volume histograms for patient-based approach with microsphere-number densities of 200, 1,000, 10,000, and 50,000 spheres/mL: tumor 2 (A), tumor 9 (B), and tumor 13 (C). Absorbed dose is reported as fraction of average absorbed dose. Davg = average absorbed dose to tumor volume.

  • FIGURE 7.
    FIGURE 7.

    Line profile showing absorbed dose across section of tumor with uniform macroscopic deposition. Data for 100-Gy average dose are presented at microsphere-number densities of 50,000 and 2,500 spheres/mL. Characteristic higher peaks and lower troughs at lower microsphere-number densities are apparent. Data are also presented at 2,500 spheres/mL at 130-Gy average absorbed-dose endpoint, consistent with lower limit of recommended treatment activity for radioembolization using glass microspheres. This increase in average tumor-absorbed dose easily overcomes differences due to microsphere-number density.

Tables

  • TABLE 1

    Overview of Resin and Glass 90Y Radioembolization Products

    CharacteristicSIR-SpheresTheraSphere
    CompositionResin with 90Y bound to surfaceGlass permanently impregnated with 90Y
    Size32.5 ± 5 μm20–30 μm
    Number of spheres per vial40–80 million1.2–8 million
    Specific activity at calibration50 Bq/sphere2500 Bq/sphere
    Time after infusion when 90% of absorbed dose is delivered∼9 d∼9 d
    Shelf life from time of calibration24 h12 d
    Specific activity at treatment50–38.6* Bq/sphere2,500–111* Bq/sphere
    Range of microsphere-number density per gray of average tumor-absorbed dose†413–535 mL-Gy−18.2–186 mL-Gy−1
    Range of microsphere-number density at…
     100-Gy average tumor-absorbed dose41,300–53,500 mL−1820–18,600 mL−1
     250-Gy average tumor-absorbed dose103,250–133,750 mL−12,050–46,500 mL−1

    • ↵* Based on decay at expiration/shelf-life of product.

    • ↵† Based on clinical specific activity range.

    • Adapted from Salem and Thurston (4).

  • TABLE 2

    Summary of 90Y PET/CT Patient Data Used

    PatientTumorTypeSize (cm)
    11Hepatocellular carcinoma7 × 9.2 × 11
    22Adenocarcinoma1.9 × 2.5 × 4.2
    33Adenocarcinoma3.8 × 3.4 × 3.4
    44Hepatocellular carcinoma4.4 × 4.6 × 3.1
    55Cholangiocarcinoma3.1 × 2.3 × 2.8
    56Cholangiocarcinoma4.7 × 5.8 × 6.1
    57Cholangiocarcinoma3.0 × 3.1 × 2.3
    68Breast cancer2.7 × 2.3 × 2.3
    79Hepatocellular carcinoma15 × 9.4 × 10.4
    810Hepatocellular carcinoma9.3 × 7.1 × 6.8
    911Hepatocellular carcinoma2.1 × 2.5 × 3.1
    912Hepatocellular carcinoma2.8 × 2.9 × 2.1
    913Hepatocellular carcinoma3.1 × 3.2 × 3.5
    914Hepatocellular carcinoma2.8 × 3.1 × 2.9
    1015Hepatocellular carcinoma8.7 × 8.9 × 12.3
    1116Neuroendocrine1.1 × 1.3 × 2.6
    1117Neuroendocrine2.6 × 2.0 × 1.2
    1218Hepatocellular carcinoma4.9 × 6.6 × 9.1
    1319Hepatocellular carcinoma6.2 × 4.5 × 5.1

    • All tumors were treated with resin microspheres, and none of the tumors reached stasis.

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