Research ArticleFEATURED BASIC SCIENCE ARTICLE

The Emission of Internal Conversion Electrons Rather Than Auger Electrons Increased the Nucleus-Absorbed Dose for 161Tb Compared with 177Lu with a Higher Dose Response for [161Tb]Tb-DOTA-LM3 Than for [161Tb]Tb-DOTATATE

Kaat Spoormans, Lara Struelens, Koen Vermeulen, Marijke De Saint-Hubert, Michel Koole and Melissa Crabbé
Journal of Nuclear Medicine October 2024, 65 (10) 1619-1625; DOI: https://doi.org/10.2967/jnumed.124.267873

Article Figures & Data

Figures

  • Figure
  • FIGURE 1.
    FIGURE 1.

    Clonogenic survival of CA20948 cells after treatment with [161Tb]Tb- and [177Lu]Lu-DOTATATE and -DOTA-LM3 as function of added activity concentration (MBq/mL). Error bars are defined as ±1 SD (N = 3, n = 6).

  • FIGURE 2.
    FIGURE 2.

    Saturation binding assay representing total binding and nonspecific binding for different added activity concentrations of [161Tb]Tb-DOTATATE with fixed molar activity of 100 MBq/nmol. Error bars are defined as ±1 SD (N = 3, n = 3).

  • FIGURE 3.
    FIGURE 3.

    (A) Association kinetics during 4 h of incubation with 0.024, 0.78 and 12.5 nM [161Tb]Tb-DOTATATE. (B and C) Dissociation kinetics of 1 nM [177Lu]Lu-DOTATATE (B) and [177Lu]Lu-DOTA-LM3 (C) for all compartments (internalized, cell membrane, and medium fraction). Error bars are defined as ±1 SD (N = 3, n = 2).

  • FIGURE 4.
    FIGURE 4.

    Total absorbed dose to cell nucleus for range of added activity concentrations of both 161Tb- and 177Lu-labeled DOTATATE and DOTA-LM3. Error bands represent ±1 SD.

  • FIGURE 5.
    FIGURE 5.

    Absorbed dose to cell nucleus, corresponding to 1 MBq/mL of respective radioligands depicted in x-axis, and contributions from different particles (A) and source regions (B). Error bars are defined as ±1 SD of total absorbed dose calculated over all particle types or all source regions.

  • FIGURE 6.
    FIGURE 6.

    Clonogenic survival curves plotted against absorbed dose in cell nucleus (Gy), shown per peptide (A and B) or per radioisotope (C and D). All data are fitted to linear model except for [161Tb]Tb-DOTA-LM3, which is fitted to linear-quadratic model. Fitting parameters are summarized in Table 1. Error bars correspond to ±1 SD, whereas error bands represent 95% confidence interval of curve fit.

Tables

  • TABLE 1.

    Fitting Parameters of Survival Curves

    Parameter[177Lu]Lu-DOTATATE[161Tb]Tb-DOTATATE[177Lu]Lu-DOTA-LM3[161Tb]Tb-DOTA-LM3
    Best fit*LinearLinearLinearLinear-quadratic
    α (Gy−1)0.100 ± 0.0120.111 ± 0.0050.049 ± 0.0090.000 ± 0.025
    β (Gy−2)———0.017 ± 0.004
    RBEmax†0.48 ± 0.170.53 ± 0.180.23 ± 0.09—‡
    RBE500.31 ± 0.110.35 ± 0.12—§0.33 ± 0.12
    RBE10—§0.24 ± 0.05—§0.42 ± 0.08

    • ↵* Based on extra-sum-of-squares F test.

    • ↵† Reference source for RBE was 137Cs source (α = 0.210 ± 0.070 Gy−1 and β = 0.050 ± 0.020 Gy−2 from Chan et al. (21)).

    • ↵‡ RBEmax not valid for α = 0.

    • ↵§ Because this radiopeptide did not reach 50% or 10% survival in colony survival assay, corresponding RBE value was not calculated.

    • RBE50 and RBE10 are RBEs with survival fractions of 10% and 50%, respectively.

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