Targeted alpha therapy with 212 Pb or 225 Ac: Change in RBE from daughter migration.

Autor: Ackerman NL; Department of Physics and Astronomy, Agnes Scott College, Decatur, GA, USA. Electronic address: nackerman@agnesscott.edu., de la Fuente Rosales L; Departamento de Física Aplicada, Instituto de Física 'Gleb Wataghin', UNICAMP, Campinas, Brazil., Falzone N; CR-UK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom., Vallis KA; CR-UK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom., Bernal MA; Departamento de Física Aplicada, Instituto de Física 'Gleb Wataghin', UNICAMP, Campinas, Brazil.
Jazyk: angličtina
Zdroj: Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB) [Phys Med] 2018 Jul; Vol. 51, pp. 91-98. Date of Electronic Publication: 2018 May 25.
DOI: 10.1016/j.ejmp.2018.05.020
Abstrakt: Targeted α-therapy (TAT) could be delivered early to patients who are at a high-risk for developing brain metastases, targeting the areas of the vasculature where tumor cells are penetrating into the brain. We have utilized a Monte Carlo model representing brain vasculature to calculate physical dose and DNA damage from the α-emitters 225 Ac and 212 Pb. The micron-scale dose distributions from all radioactive decay products were modeled in Geant4, including the eV-scale interactions using the Geant4-DNA models. These interactions were then superimposed on an atomic-scale DNA model to estimate strand break yields. In addition to 225 Ac having a higher dose per decay than 212 Pb, it also has a double strand break yield per decay that is 4.7 ± 0.5 times that of 212 Pb. However, the efficacy of both nuclides depends on retaining the daughter nuclei at the target location in the brain vasculature. The relative biological effectiveness (RBE) of 225 Ac and 212 Pb are similar when the entire decay chains are included, with maxima of 2.7 ± 0.6 and 2.5 ± 0.5 (respectively), and RBE values of about 2 to a depth of 80 μm. If the initial daughter is lost, the RBE of 212 Pb is completely reduced to 1 or lower and the RBE of 225 Ac is approximately 2 only for the first 40 μm.
(Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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