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A reanalysis of nanoparticle tumor delivery using classical pharmacokinetic metrics

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Science Advances  15 Jul 2020:
Vol. 6, no. 29, eaay9249
DOI: 10.1126/sciadv.aay9249
  • Fig. 1 Comparisons between %ID in tumor and traditional PK metrics for all datasets (i.e., all types of nanoparticles).

    Correlation plots for all datasets between %ID in tumor (per Wilhelm et al.) and AUCtumor/AUCblood ratio (%) (A), RDI-OT AUCtumor (B), and tumor Cmax (C). Plots are shown with all datasets (i, outliers shown as □) and with outliers excluded (ii). There was no relationship between %ID in tumor and AUCtumor/AUCblood ratio (%) [ρ = 0.183 all data (AD); ρ = 0.151 excluding outliers (EO)] and a weak relationship between %ID in tumor and RDI-OT AUCtumor (ρ = 0.319 AD; ρ = 0.289 EO). There was a moderate relationship between %ID in tumor and the tumor Cmax (ρ = 0.562 AD; ρ = 0.572 EO).

  • Fig. 2 Comparisons between %ID in tumor and traditional PK metrics in the liposome subset.

    Correlation plots for the liposome subset between %ID in tumor (per Wilhelm et al.) and AUCtumor/AUCblood ratio (%) (A), RDI-OT AUCtumor (B), and tumor Cmax (C). Plots are shown with all liposome datasets (i, outliers shown as □) and with outliers excluded (ii). There was no relationship between %ID in tumor and AUCtumor/AUCblood ratio (%) (ρ = 0.145 AD; ρ = 0.023 EO) and no relationship between %ID in tumor and RDI-OT AUCtumor (ρ = 0.150 AD; ρ = 0.029 EO). There was a weak relationship between %ID in tumor and the tumor Cmax (ρ = 0.412 AD; ρ = 0.514 EO).

  • Fig. 3 Comparisons between %ID in tumor and traditional PK metrics in the polymetric subset.

    Correlation plots for the polymeric subset between %ID in tumor (per Wilhelm et al.) and AUCtumor/AUCblood ratio (%) (A), RDI-OT AUCtumor (B), and tumor Cmax (C). Plots are shown with all polymeric datasets (i, outliers shown as □) and with outliers excluded (ii). There was no relationship between %ID in tumor and AUCtumor/AUCblood ratio (%) (ρ = 0.094 AD; ρ = 0.097 EO) and a weak relationship between %ID in tumor and RDI-OT AUCtumor (ρ = 0.422 AD; ρ = 0.447 EO). There was a moderate relationship between %ID in tumor and the tumor Cmax (ρ = 0.547 AD; ρ = 0.519 EO).

  • Fig. 4 Comparisons between %ID in tumor and traditional PK metrics in the inorganic subset.

    Correlation plots for the inorganic subset between %ID in tumor (per Wilhelm et al.) and AUCtumor/AUCblood ratio (%) (A), RDI-OT AUCtumor (B), and tumor Cmax (C). Plots are shown with all inorganic datasets (i, outliers shown as □) and with outliers excluded (ii). There was no relationship between %ID in tumor and AUCtumor/AUCblood ratio (%) (ρ = 0.265 AD; ρ = 0.243 EO) and a weak relationship between %ID in tumor and RDI-OT AUCtumor (ρ = 0.322 AD). There was a moderate relationship between %ID in tumor and the tumor Cmax (ρ = 0.618 AD; ρ = 0.605 EO).

  • Fig. 5 Example concentration versus time profiles of NPs in blood (left y axis) and tumor (right y axis) and PK metric calculation.

    The concentration versus time profile in blood is represented by the red symbols and lines. The concentration versus time profile in tumor is represented by the blue symbols and lines. The dotted red and blue lines represent the approximate variability in interquartile range for the blood and tumor concentration versus time profiles, respectively. The dashed gray line represents a constant tumor concentration of 3.5 %ID/g that yields the same AUCtumor (250 hours*%ID/g) as the actual tumor concentration versus time profile. The %ID in tumor calculated by Wilhelm et al. of 0.7% is the average %ID found in the tumor at every 1-hour interval throughout the entire PK evaluation period and is represented by the vertical white and green bar.

  • Table 1 Median and interquartile range values for all calculated PK metrics.

    Median (interquartile range)All subsets combinedLiposome subsetPolymeric subsetInorganic subset
    %ID in tumor0.67 (0.36–1.19)0.55 (0.31–2.17)0.68 (0.42–1.26)0.64 (0.35–1.14)
    AUCtumor/AUCblood ratio (%)76.12 (48.79–158.81)45.46 (31.16–63.48)143.94 (56.00–318.87)81.44 (55.01–135.92)
    RDI-OT AUCtumor59.64 (26.54–158.60)74.63 (39.77–100.89)48.69 (23.55–160.48)63.75 (26.68–209.85)
    Tumor Cmax (%ID/g)4.71 (2.65–7.97)3.92 (2.71–7.07)6.26 (3.05–10.22)4.21 (2.46–6.57)

Supplementary Materials

  • Supplementary Materials

    A reanalysis of nanoparticle tumor delivery using classical pharmacokinetic metrics

    Lauren S. L. Price, Stephan T. Stern, Allison M. Deal, Alexander V. Kabanov, William C. Zamboni

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