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OtherBASIC SCIENCE INVESTIGATIONS

Log Normal Distribution of Cellular Uptake of Radioactivity: Implications for Biologic Responses to Radiopharmaceuticals

Prasad V.S.V. Neti and Roger W. Howell
Journal of Nuclear Medicine June 2006, 47 (6) 1049-1058;
Prasad V.S.V. Neti
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Roger W. Howell
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  • FIGURE 1. 
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    FIGURE 1. 

    Initial mean cellular activity <ao> as function of activity concentration C of 210Po-citrate in culture medium for representative experiment. Error bars represent SD of mean for 3 replicate measurements of <ao> and C. Solid line represents linear least-squares fit of the data.

  • FIGURE 2. 
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    FIGURE 2. 

    Autoradiographs of cells within a population exposed to culture medium containing 67 kBq/mL of 210Po-citrate. These images show cells with 0, 1, 3, 5, 7, and >9 α-particle tracks, demonstrating wide variation in cellular uptake of 210Po-citrate.

  • FIGURE 3. 
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    FIGURE 3. 

    Distribution of α-particle tracks in cells that were incubated in culture medium containing 210Po-citrate: 0.52 kBq/mL (A), 3.8 kBq/mL (B), 67 kBq/mL (C). <ao> was 0.054, 0.12, and 1.8 mBq per cell in A, B, and C, respectively. Decays were allowed to accumulate for different times, as indicated in the keys in A–C.

  • FIGURE 4. 
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    FIGURE 4. 

    Distribution of convolved α-particle tracks (lower abscissae) and initial cellular activity (upper abscissae) in cell populations having mean activity per cell <ao> of 0.054 mBq per cell (A), 0.12 mBq per cell (B), and 1.8 mBq per cell (C). α-Particle tracks are result of convolving the data shown in Figure 3. Data arising from different decay accumulation times are denoted with different symbols: (A) 52 d (•), 26 d (▪), 7 d (▴); (B) 4 d (•), 0.67 d (▴); and (C) 1 d (•), 0.25 d (▴). The close correspondence of convolved data from different time points supports the accuracy of the convolution approach. Error bars represent SE. Cellular activity was calculated from track data using Equation 3. Curve represents least-squares fit of Equation 5 to convolved track data. Details regarding fitted parameters and corresponding statistical quantities are given in Table 1. Parameters related to cellular activity are given in Table 2.

  • FIGURE 5. 
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    FIGURE 5. 

    Log normal probability density function f(ao) vs. initial cellular activity ao for 3 different mean cellular activities <ao>: 0.054 mBq per cell (A), 0.12 mBq per cell (B), 1.8 mBq per cell (C). Probability density functions were obtained using Equation 9 and parameters μa and σ from Table 2.

  • FIGURE 6. 
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    FIGURE 6. 

    Calculated cell survival fraction (SF) vs. mean activity per cell <ao> assuming a log normal distribution of activity per cell. Survival fractions were calculated for different values of σ according to Equation 14. Shaded region represents range of σ values that were observed for various 210Po activities used in the present studies. Condition σ → 0 represents the case where all cells in the population contain the same activity (i.e., SF = exp(−<ao>/a37). Note profound impact that shape parameter σ has on survival curve.

Tables

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    TABLE 1

    Fitted Parameters and Statistical Quantities for Log Normal Convolved Track Distributions

    ParameterValue
    ExperimentABC
    Labeling concentration (kBq/mL)*0.52 ± 0.0513.8 ± 0.3667 ± 6.6
    Mean cellular activity <ao> (mBq/cell)*0.054 ± 0.00370.12 ± 0.0111.8 ± 0.22
    Maximum time of emulsion exposure (d)5241
    Scale parameter (μN)†1.6 ± 0.0721.8 ± 0.0271.8 ± 0.031
    Shape parameter (σ)†0.80 ± 0.0560.59 ± 0.0230.54 ± 0.029
    Goodness of fit (R2)0.920.980.97
    Arithmetic mean <N> (convolved tracks/cell)‡7.1 ± 0.636.9 ± 0.226.7 ± 0.25
    Median (convolved tracks/cell)‡5.2 ± 0.375.8 ± 0.165.8 ± 0.18
    Mode (convolved tracks/cell)‡2.7 ± 0.314.2 ± 0.164.3 ± 0.19
    Variance‡45 ± 1320 ± 2.315 ± 2.3
    Skewness‡3.7 ± 0.512.2 ± 0.121.9 ± 0.14
    Kurtosis‡34 ± 1012 ± 1.210 ± 1.2
    Coefficient of variation (CV)0.940.640.58
    Cumulative probability for 1−9 tracks (%)747779
    Cumulative probability for 10−40 tracks (%)201815
    Cumulative probability for <1 track (%)2.00.130.053
    • ↵* Errors are based on SD of triplicate measurements of scintillation counts and cell counts.

    • ↵† Errors are provided by least-squares fits to data using Sigmaplot (SPSS).

    • ↵‡ Errors are derived using the general form:Embedded Imagewhere ξ2 is variance.

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    TABLE 2

    Fitted Parameters and Statistical Quantities for Log Normal Activity Distributions

    ParameterValue
    ExperimentABC
    Labeling concentration (kBq/mL)*0.52 ± 0.0513.8 ± 0.3667 ± 6.6
    Mean cellular activity <ao> (mBq/cell)*0.054 ± 0.00370.12 ± 0.0111.8 ± 0.22
    Scale parameter (μa)†−3.2 ± 0.11−2.3 ± 0.0280.43 ± 0.029
    Shape parameter (σ)†0.80 ± 0.0560.59 ± 0.0230.52 ± 0.026
    Arithmetic mean (ao) (mBq/cell)‡0.054 ± 0.00660.12 ± 0.00411.8 ± 0.062
    Median (mBq/cell)‡0.039 ± 0.00410.11 ± 0.00291.5 ± 0.046
    Mode (mBq/cell)‡0.021 ± 0.00320.074 ± 0.00291.2 ± 0.047
    • ↵* †‡Errors are obtained as described in Table 1.

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Journal of Nuclear Medicine: 47 (6)
Journal of Nuclear Medicine
Vol. 47, Issue 6
June 2006
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Log Normal Distribution of Cellular Uptake of Radioactivity: Implications for Biologic Responses to Radiopharmaceuticals
Prasad V.S.V. Neti, Roger W. Howell
Journal of Nuclear Medicine Jun 2006, 47 (6) 1049-1058;

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Log Normal Distribution of Cellular Uptake of Radioactivity: Implications for Biologic Responses to Radiopharmaceuticals
Prasad V.S.V. Neti, Roger W. Howell
Journal of Nuclear Medicine Jun 2006, 47 (6) 1049-1058;
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