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  • br inhibitors W stemann et al Thus

    2022-05-25


    inhibitors (Wüstemann et al., 2016). Thus, the general radio-biokinetic
    models for iPSMA in the CS and Cy of LNCaP D-Luciferin 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).
    Table 2 shows the average absorbed dose per nuclear transforma-
    blem of recoil energy of the nucleus during decay, which can provoke
    progeny, as well as for 177Lu. As can be observed in Table 3, 225Ac- the breaking of the bond with the molecule chelator, allowing the re-
    iPSMA releases a nine hundred-fold greater radiation dose than 177Lu- lease of the daughter radionuclide from the chelate. However, as in the
    iPSMA and 14 times more than 223 RaCl2 per unit of activity retained in case of radio-lanthanides used as bone-seeking agents (e.g. 153Sm+3
    and 177 Lu +3 ), it is highly probable that free radionuclides remain as
    bone. Although high dose values are observed per Bq in the bone model
    immobile compounds in the osseous tissue and also position themselves
    of 223RaCl2 or 225Ac-iPSMA to patients is around 7 MBq (Nilsson et al., extremely close to cancer cells. (Volkert and Hoffman, 1999; Yoshida
    2007; Kratochwil et al., 2018); therefore, the maximum activity ex- et al., 2016). Nevertheless, experimental models are necessary to
    evaluate the RBE value of 225Ac-iPSMA and the biodistribution of free
    225Ac daughter radionuclides in bone as a consequence of the recoil
    bone) is in the order of μBq. In the case of 177Lu-iPSMA, the adminis-
    iPSMA, which signifies that in clinical applications both radio- 4. Conclusions
    pharmaceuticals are delivering the same radiation absorbed dose to 225Ac-iPSMA has potential dosimetric and radiobiological ad-
    cancer cells in patients. However, in this issue the RBE effect is relevant