Research ArticleContinuing Education

The MIRD Schema for Radiopharmaceutical Dosimetry: A Review

Pat Zanzonico
Journal of Nuclear Medicine Technology March 2024, jnmt.123.265668; DOI: https://doi.org/10.2967/jnmt.123.265668

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    (A) Family of stylized reference phantoms from ORNL (22). Each phantom has both male and female sex organs. (B) Family of voxel-based reference phantoms from ICRP (18,23). Total of 12 phantoms are in ICRP reference series. In this figure, only male versions are shown for ages below 15 y. (Reprinted from (3).)

  • FIGURE 2.
    FIGURE 2.

    Ratio (median) of 131I S values for ICRP voxel-based phantoms to values for ORNL stylized phantoms for selected source-region/target-region pairs. (Reprinted from (24).)

  • FIGURE 3.
    FIGURE 3.

    (A) Idealized exponentially decreasing time–activity curves illustrating relationship among physical, biologic, and effective half-times in tissue or organ for administered radiopharmaceutical. Each curve is characterized by clearance constant and corresponding half-time, with effective clearance constant being greater than either physical or biologic clearance constant (Eq. 18) and effective half-time being shorter than either physical or biologic half-time (Eq. 23). (Reprinted from (3).) (B) Actual time–activity curve will be more complex, including rising component at early times after administration as radiopharmaceutical exits blood and enters tissue parenchyma of organ. In many cases, this rising portion of time–activity curve is brief compared with remainder of curve and is therefore ignored in fitting mathematic function to curve for purpose of estimating time-integrated activity. More specifically, although fitting of monotonically decreasing exponential function to organ’s time–activity data will overestimate total time-integrated activity to infinite time (i.e., corresponding to complete decay of administered radionuclide), magnitude of this overestimate will be small for small-molecule radiopharmaceuticals. However, for slowly localizing, large-molecule radiopharmaceuticals such as radiolabeled antibodies, this overestimate of time-integrated activity may be significant. Graphically, total time-integrated activity (i.e., area under curve) for actual time–activity curve (represented by upper left–to–lower right slant-line hatching) will be overestimated by amount corresponding to lower left–to–upper right slant-line hatching.

  • FIGURE 4.
    FIGURE 4.

    General workflow for radiopharmaceutical therapy dosimetry. Test administration may be either pretherapy tracer administration or first cycle of multidose therapy regimen. Calculation of absorbed doses (in terms of either tumor and organ mean doses or dose distributions) or of dose rates D is performed using dose factors (e.g., S values), dose point kernels, or Monte Carlo analysis. Physical dosimetry yields absorbed dose, and bioeffect dosimetry yields dose metrics such as biologically effective dose, equieffective dose, or effective uniform dose (for bioeffect dosimetry). (Reprinted from (40).)

Tables

  • TABLE 1.

    Terminology and Nomenclature Used in MIRD Schema (1–3)

    Unit*
    ParameterSymbolDefinitionSIOlderComment
    Administered activityEmbedded ImageActivity of radiopharmaceutical administered to patientMBqmCiBase SI unit of activity is becquerel (≡1 disintegration per second [dps]); older unit of activity, curie, corresponds to 3 × 1010 dps; 37 MBq equals 1 mCi and 37 kBq equals 1 μCi; it is important to distinguish activity administered (often mistakenly referred to as dose) from actual radiation dose
    Source regionEmbedded ImageRegion (such as tissue or organ) containing radionuclide and within which radiation is emitted as radionuclide undergoes decayNot applicableNot applicable
    Target regionEmbedded ImageRegion (such as tissue or organ) within which energy of emitted radiations is depositedNot applicableNot applicableFor systemically administered and distributed radiopharmaceutical, every tissue or organ is both source and target region
    TimetTime after administration of radiopharmaceuticalhhTime of administration of radiopharmaceutical is designated as time zero, that is, as t = 0
    ActivityEmbedded ImageActivity in source region Embedded Image at time tMBqmCiPlot of activity in source region Embedded Image vs. time t is source-region time–activity curve
    Time-integrated activityEmbedded ImageNumber of radioactive decays in source region Embedded Image from time t = 0 to time t = τMBq-sμCi-hEmbedded Image; integration time τ is commonly set to infinity, yielding total number of decays in source region Embedded Image for complete decay of administered radionuclide; time-integrated activity was originally called cumulated activity
    Time-integrated activity coefficient†Embedded ImageNumber of radioactive decays in source region Embedded Image from time t = 0 to time t = τ per unit administered activityMBq-s MBq−1μCi-h mCi−1Embedded Image; time-integrated activity coefficient was originally called residence time
    Absorbed doseEmbedded ImageAbsorbed dose to target region Embedded Image from time t = 0 to time t = τGyradIntegration time τ is commonly set to infinity, yielding total absorbed dose to target region Embedded Image for complete decay of administered radionuclide
    Absorbed dose coefficientEmbedded ImageAbsorbed dose to target region Embedded Image from time t = 0 to time t = τ per unit administered activityGy MBq−1rad mCi−1Embedded Image
    MassEmbedded ImageMass of source region Embedded Image and target region Embedded Image, respectivelygg
    EnergyEmbedded ImageEnergy (or mean energy) per particle or photon of ith radiation emitted by administered radionuclideMeVMeV
    Number of radiations per decayEmbedded ImageNumber of ith radiation emitted per radioactive decay for administered radionuclideNot applicableNot applicable
    Energy per decayEmbedded ImageEnergy (or mean energy) of ith radiation emitted by administered radionuclide per radioactive decayMeVMeVEmbedded Image
    Absorbed fractionEmbedded ImageAbsorbed fraction, that is, fraction of energy Embedded Image of ith radiation emitted within source region Embedded Image that is absorbed in target region Embedded ImageNot applicableNot applicable
    Specific absorbed fractionEmbedded ImageSpecific absorbed fraction, that is, fraction of energy Embedded Image of ith radiation emitted within source region Embedded Image that is absorbed in target region Embedded Image per unit mass of target region Embedded Imageg−1g−1Embedded Image
    S valueEmbedded ImageAbsorbed dose to target region Embedded Image per radioactive decay in target region rmGy MBq−1 s−1rad μCi−1 h−1Embedded Image

    • ↵* Although older units are presented for completeness, SI units should be used exclusively.

    • ↵† In modern MIRD-schema nomenclature (1), dosimetric quantity normalized to administered activity is identified by term coefficient appended to quantity name.

  • TABLE 2.

    S Values for 131I-Derived from ICRP Voxel-Based Computational Phantom of Reference Adult Male (18)

    Source regionTarget region
    AdrenalsBrainGallbladder wallHeart wallKidneysLiverLungMusclePancreasSpleenStomach wallThymusThyroidUrinary bladder wall
    Adrenals1.81E−038.14E−092.05E−066.72E−076.95E−062.02E−065.76E−072.05E−072.18E−063.63E−061.66E−061.62E−079.69E−085.21E−08
    Brain8.52E−092.70E−058.18E−092.84E−085.55E−091.26E−084.27E−086.17E−086.16E−091.26E−089.22E−098.29E−081.60E−072.97E−10
    Gallbladder content1.88E−067.38E−096.79E−055.59E−071.56E−064.56E−064.14E−071.47E−076.14E−064.00E−071.39E−061.48E−077.78E−087.19E−08
    Heart content6.76E−072.46E−085.68E−079.22E−063.50E−079.19E−071.85E−061.57E−076.12E−079.65E−071.60E−061.69E−065.35E−071.48E−08
    Kidneys6.97E−065.02E−091.60E−063.49E−078.60E−051.21E−062.92E−072.24E−072.11E−061.74E−061.01E−068.97E−085.42E−089.79E−08
    Liver2.02E−061.19E−085.32E−069.77E−071.21E−061.82E−058.13E−071.65E−071.95E−064.18E−071.38E−062.49E−071.35E−074.52E−08
    Lungs5.52E−074.33E−084.23E−072.11E−062.84E−078.18E−073.04E−052.23E−073.56E−079.65E−076.67E−072.07E−061.05E−061.15E−08
    Muscle2.06E−078.49E−081.51E−071.71E−072.27E−071.69E−072.30E−071.41E−061.61E−072.06E−071.61E−072.06E−072.65E−073.12E−07
    Pancreas2.17E−065.40E−096.95E−066.15E−072.11E−061.96E−063.55E−071.56E−072.07E−049.80E−073.77E−061.20E−076.47E−089.54E−08
    Small intestine content1.21E−063.04E−091.35E−062.99E−071.73E−066.75E−071.87E−071.99E−073.38E−068.30E−071.64E−066.01E−083.46E−084.92E−07
    Spleen3.66E−061.17E−084.25E−079.56E−071.74E−064.20E−071.03E−062.00E−079.77E−071.56E−042.54E−061.97E−071.40E−073.26E−08
    Stomach content1.57E−068.29E−091.19E−061.79E−061.02E−061.18E−066.58E−071.51E−073.00E−062.35E−065.89E−051.99E−071.05E−075.05E−08
    Thymus1.64E−078.24E−081.55E−072.33E−069.23E−082.59E−071.83E−061.93E−071.29E−072.04E−072.13E−071.14E−038.41E−064.48E−09
    Thyroid9.72E−081.62E−078.07E−086.49E−075.60E−081.38E−079.30E−072.40E−076.75E−081.39E−071.11E−078.25E−061.44E−032.49E−09
    Urinary bladder content5.64E−082.83E−107.43E−081.58E−081.05E−074.69E−081.21E−083.14E−071.05E−073.36E−085.53E−084.93E−092.74E−092.19E−05

    • Data are mGy MBq−1 s−1. ICRP voxel-based phantoms actually include many more source and target regions than those tabulated here, but for readability only partial list of S values is presented. (Adapted from reference (19).)

  • TABLE 3.

    Classification of Computational Anatomic Phantoms by Format and Morphometric Category (3)

    ParameterClass 1Class 2Class 3Class 4
    Format*Stylized: organs and total body represented by regular 3-dimensional shapes such as spheres and ellipsoids.Voxel: CT- or MRI-based 3-dimensional digital representation of segmented organ as assemblies of cubic volume elements (or voxels)NURBS (nonuniform rational B-spline): anatomic volumes defined by NURBS equations characterized by set of control points; shape and volume of NURBS surface vary with coordinates of control pointsPolygon mesh-based: Polygonal mesh is composed of set of vertices, edges, and faces that specify shape of polyhedral object in 3 dimensions; surfaces of phantom are defined by large number of polygonal meshes such as tetrahedrons
    Category†Reference: average human anatomy corresponding, for example, to men and women at roughly 50th percentile for heights and weights at discrete ages (newborn, 1-y-old, 5-y-old, 10-y-old, 15-y-old, and adult); there is no match to anatomy of any specific patient; S values can be precomputed for all source/target organ combinations in reference phantom seriesPatient-dependent: use of computational phantom library covering various combinations of height and weight percentiles in modeled patient population; internal organ anatomy is volumetrically rescaled to outer body size (contour) but is not patient-specific; S values can be precomputed for all source/target organ combinations for each member of patient-dependent phantom libraryPatient-sculpted: use of computational methods to change body contour of selected patient-dependent phantom from phantom library; resulting phantom would then appear to have same body size and shape as that of patient, but again, internal organ anatomy is not patient-specific; as patient-sculpted phantom does not exist until it is created (using patient’s CT/MR-based body contour), S values cannot be precomputed but must be generated by Monte Carlo computer simulation once that phantom is availablePatient-specific: matching of phantom internal and external anatomy to CT- or MRI-measured anatomy of specific patient; as with patient-sculpted phantoms, S values cannot be precomputed until patient-specific phantom is developed

    • ↵* From left to right, classes require increasing computer memory.

    • ↵† From left to right, classes involve improving anatomic fidelity.

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