The objectives of the present study were (1) to present a comprehensive analysis of the microdosimetric quantities in both human and rat bronchial airways and (2) to assess the contribution of the crossfire alpha particles emitted from the alveolar region to bronchial absorbed doses. Hit frequencies, absorbed doses and critical microdosimetric quantities were calculated for basal and secretory cell nuclei located at different depths in epithelial tissue for each bronchial airway generation for defined exposure conditions. Total absorbed doses and hit frequencies were slightly higher in rat airways than in corresponding human airways. This confirms the a priori assumption in rat inhalation experiments that the rat lung is a suitable surrogate for the human lung. While the contribution of crossfire alpha particles is insignificant in the human lung, it can reach 33% in peripheral bronchiolar airways of the rat lung. The latter contribution may even further increase with increasing alveolar 214Po activities. Hence, the observed prevalence of tumors in the bronchiolar region of the rat lung may partly be attributed to the high-linear energy transfer crossfire alpha particles.
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http://dx.doi.org/10.1093/rpd/ncm496 | DOI Listing |
Introduction: Metastatic castration-resistant prostate cancer (mCRPC) is the most severe form of prostate cancer, developing in about 30% of patients; standard approaches of its treatment often remain ineffective. The development of theranostics principle and the discovery of the prostate-specific membrane antigen (PSMA) make it possible to implement a new approach in the treatment of patients with mCRPC - PSMA-targeted therapy. It is based on the use of a specific radionuclide (alpha or beta-minus emitter) associated with a ligand (radioligand) that binds to PSMA and has a targeted effect on tumor cells.
View Article and Find Full Text PDFFor many years in radiobiology and radiotherapy predominated the conviction that cellular DNA is the main target for ionizing radiation, however, the view has changed in the past 20 years. Nowadays, it is assumed that not only directed (targeted) radiation effect, but also an indirect (non-targeted) effect may contribute to the result of radiation treatment. Non-targeted effect is relatively well recognized after external beam irradiation in vitro and in vivo, and comprises such phenomena like radiation-induced bystander effect (RIBE), genomic instability, adaptive response and abscopal (out of field) effect.
View Article and Find Full Text PDFAdv Drug Deliv Rev
January 2017
Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada; Department of Medical Imaging, University of Toronto, Toronto, ON, Canada; Toronto General Research Institute and Joint Department of Medical Imaging, University Health Network, Toronto, ON, Canada. Electronic address:
Radioimmunotherapy (RIT) aims to selectively deliver radionuclides emitting α-particles, β-particles or Auger electrons to tumors by conjugation to monoclonal antibodies (mAbs) that recognize tumor-associated antigens/receptors. The approach has been most successful for treatment of non-Hodgkin's B-cell lymphoma but challenges have been encountered in extending these promising results to the treatment of solid malignancies. These challenges include the low potency of β-particle emitters such as I, Lu or Y which have been commonly conjugated to the mAbs, due to their low linear energy transfer (LET=0.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2015
Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
Despite significant advances in the treatment of Hodgkin's lymphoma (HL), a significant proportion of patients will not respond or will subsequently relapse. We identified CD25, the IL-2 receptor alpha subunit, as a favorable target for systemic radioimmunotherapy of HL. The scientific basis for the clinical trial was that, although most normal cells with exception of Treg cells do not express CD25, it is expressed by a minority of Reed-Sternberg cells and by most polyclonal T cells rosetting around Reed-Sternberg cells.
View Article and Find Full Text PDFNucl Med Commun
December 2014
aTranslational Oncology Laboratory, Centre for Cancer Biology, SA Pathology bSchool of Medicine cSchool of Chemistry and Physics, University of Adelaide dDepartment of Medical Physics eCancer Clinical Trials Unit, Royal Adelaide Hospital fEnvironment Protection Authority SA, Adelaide, Australia.
Resistance to conventional cancer treatments is a major problem associated with solid tumours. Tumour hypoxia is associated with a poor prognosis and with poor treatment outcomes; therefore, there is a need for treatments that can kill hypoxic tumour cells. One potential option is targeted α-radioimmunotherapy, as α-particles can directly kill hypoxic tumour cells.
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