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  • br bk Branching fraction for daughter radionuclide k

    2020-08-12


    bk = Branching fraction for daughter radionuclide “k”. Nj = Total number of nuclear transformations from each daughter radinuclide “k” in the “j” region (cell surface or cytoplasm for Ac-225 and its progeny, and cortical or trabecular bone for Ra-223 and its progeny).
    DFkα (n f ← j) = Absorbed dose to the cell nucleus “f” from α emis-sions per nuclear transformation (Gy/Bq.s) from decay of daughter radionuclide “k” originated in the “j” region.
    DFk (n f ← j) = Absorbed dose to the cell nucleus “f” from electron and photon emissions per nuclear transformation (Gy/Bq.s) from decay of daughter radionuclide “k” originated in the “j” region.
    In the case of 177Lu, the nuclear dose was calculated as follows:
    Fig. 3. Biokinetic model of 225Ac-iPSMA in human prostate LNCaP cells, extrapolated from the biological biokinetic model experimentally obtained with 177Lu-iPSMA in LNCaP cells.
    Finally, the average radiation absorbed dose to the nucleus of prostate cancer cells was determined as follows (eq. (5)): E. Azorín-Vega et al. Applied Radiation and Isotopes 146 (2019) 66–71
    Fig. 4. Biokinetic model of 223RaCl2 in bone, adjusted from the experimental data in six patients with prostate cancer, reported by Yoshida et al. (2016).
    Radionuclide N N N N
    Cell cytoplasm Cell membrane Trabecular Cortical
    bone bone
    177Lutetium
    its progeny
    Table 2
    Average absorbed dose per nuclear transformation (DF) values (Gy/Bq.s) of 225Ac, 223Ra and their progeny, as well as that of 177Lu to the cancer cell nucleus (n) in a simplified bone model.
    225Actinium and its progeny
    Radionuclide Half Life DF(αn ←Cy) DF(αn ←CS) DF e , ph DF e , ph
    177Lutetium
    223Radium and its progeny
    Nj = Total number of nuclear transformations in the “j” region (cell cytoplasm at 1 h, which was maintained in this proportion after 96 h.
    Therefore, the main contribution to the nuclear dose was from the cell
    DF = Absorbed dose to the nucleus from electron and photon
    . s) originated in the “j” surface (Fig. 2). This behavior was expected since the metal chelator
    azacyclododecane N,N',N'´,N'´´-tetraacetic Epirubicin (DOTA), which has been
    found as the molecule responsible for the low internalization of PSMA
    inhibitors (Wüstemann et al., 2016). Thus, the general radio-biokinetic
    models for iPSMA in the CS and Cy of LNCaP cells were established as
    3. Results and discussion
    Table 3
    Average radiation absorbed dose values (Gy/Bq) of the 225Ac, 223Ra and their progeny, as well as that of 177Lu to the cancer cell nucleus (n) in a simplified bone model. Uncertainties of the calculation are under 1%.
    225Actinium and its progeny
    Radionuclide D(n←Cy)
    α
    α
    Total dose of 225Ac and its progeny
    α
    α
    Total dose of 223Ra and its progeny
    Considering that the biokinetic behavior is mainly regulated by the more cell death per Gray (Sgouros et al., 2018). Among the advantages
    iPSMA molecule, the radio-biokinetic model for 177Lu-iPSMA and of 225Ac-iPSMA and its alpha-emitting progeny with regard to 177Lu-
    225Ac-iPSMA and its progeny were obtained by using their respective iPSMA, there are: a) generation of DNA double-strand breaks, b) in-
    λR, as shown in Figs. 2 and 3. In the case of 223RaCl2, the data fitted to dependence of cellular oxygenation (useful to eradicate hypoxic tumor
    the exponential models were established as follows (Fig. 4): cells)(Wulbrand et al., 2013), c) production of many reactive hydroxyl
    with low damage to surrounding normal tissue, due to their short path
    The total number of disintegrations (N) in each cellular compart- context, in therapies using 225Ac-iPSMA (7 MBq), not only a 14-fold
    higher radiation absorbed dose is expected with regard to those of
    ment was calculated by the integration of the A(t) functions for each
    radionuclide, as described in the methodology section. As expected, in
    found in the cytoplasm and membrane of the cancer cells, while ra-
    the case of the 225Ac and 223Ra families, the total number of disin-
    tegrations of each daughter radionuclide is practically the same as the dium-223 is located in the bone compartment. At the same time, the
    radiation absorbed dose to osteocytes (non-target cell) (approx.
    father's, due to the secular equilibrium, only influenced by the yield of
    the radionuclide decay chain (Table 1).