Sodium-iodide symporter positive cells after intracellular uptake of 99mTc versus α-emitter 211At

Summary Purpose: We evaluated the DNA damaging potential of Auger electrons emitted in the decay of 99mTc compared to α-particles of 211At. Material and methods: The impact of 99mTc and 211At was monitored in a NIS-expressing rat thyroid cell model PC Cl3 with varying, yet defined intra- and extracellular radionuclide distribution (using ± perchlorate). The radiotoxicity of 99mTc and 211At was studied by the comet assay under neutral and alkaline conditions and colony formation. Results: In the presence of perchlorate, the radioactivity yielding 37 % cellular survival, A37, was estimated to be (0.27 ± 0.02) MBq/ml and (450 ± 30) MBq/ml for 211At and 99mTc, respectively. In absence of perchlorate, cellular radiotracer uptake was similar for both radionuclides (2.2 %, 2.7 %), yet the A37 was reduced by 82% for the α-emitter and by 95 % for 99mTc. Cellular dose increased by a factor of 5 (211At) and 38 (99mTc). Comet assays revealed an increased DNA damage after intracellular uptake of both radiotracers. Conclusions: The data indicate damage to the cell to occur from absorbed dose without recognizable contribution from intracellular heterogeneity of radionuclide distribution. Comet assay under alkaline and neutral conditions did not reveal any shift to more complex DNA damage after radionuclide uptake. Cellular uptake of 99mTc and 211At increased cellular dose and reduced clonogenic survival.

[1]  R. Freudenberg,et al.  Geant4-Simulations for cellular dosimetry in nuclear medicine. , 2011, Zeitschrift fur medizinische Physik.

[2]  D. M. Lewis.  99Mo supply—the times they are a-changing , 2009, European Journal of Nuclear Medicine and Molecular Imaging.

[3]  R. Freudenberg,et al.  DNA damage in lymphocytes after irradiation with 211At and 188Re , 2009, Nuklearmedizin.

[4]  R Freudenberg,et al.  Cellular damage in vitro , 2009, Nuklearmedizin.

[5]  Liane Oehme,et al.  Dosimetry of cell-monolayers in multiwell plat , 2009, Nuklearmedizin.

[6]  A. Brill,et al.  State of the art in nuclear medicine dose assessment. , 2008, Seminars in nuclear medicine.

[7]  Amin I Kassis,et al.  Therapeutic radionuclides: biophysical and radiobiologic principles. , 2008, Seminars in nuclear medicine.

[8]  Manuel Bardiès,et al.  Cell Membrane is a More Sensitive Target than Cytoplasm to Dense Ionization Produced by Auger Electrons , 2008, Radiation research.

[9]  S. Adelstein,et al.  Auger Electron-Induced Double-Strand Breaks Depend on DNA Topology , 2008, Radiation research.

[10]  J. Ricarte-Filho,et al.  Differential gene expression analysis of iodide-treated rat thyroid follicular cell line PCCl3. , 2008, Genomics.

[11]  E. Kümmerle,et al.  On the biological efficiency of I-123 and I-125 decay on the molecular level , 2008, International journal of radiation biology.

[12]  R. Howell.  Auger processes in the 21st century , 2008, International journal of radiation biology.

[13]  B. Stenerlöw,et al.  Relative Biological Effectiveness of the α-Particle Emitter 211At for Double-Strand Break Induction in Human Fibroblasts , 2007, Radiation research.

[14]  B. Keil,et al.  Efficacy of 99mTc pertechnetate and 131I radioisotope therapy in sodium/iodide symporter (NIS)-expressing neuroendocrine tumors in vivo , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[15]  Roger W Howell,et al.  Log normal distribution of cellular uptake of radioactivity: implications for biologic responses to radiopharmaceuticals. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[16]  S. Incerti,et al.  Geant4 developments and applications , 2006, IEEE Transactions on Nuclear Science.

[17]  B. Meller,et al.  Increased Radioiodine Uptake of Thyroid Cell Cultures after External Irradiation , 2006, Strahlentherapie und Onkologie.

[18]  Nikos Agorastos,et al.  Cell uptake and radiotoxicity studies of an nuclear localization signal peptide-intercalator conjugate labeled with [99mTc(CO)3]+. , 2005, Bioconjugate chemistry.

[19]  L. Jacobsson,et al.  Myelotoxicity and RBE of 211At-conjugated monoclonal antibodies compared with 99mTc-conjugated monoclonal antibodies and 60Co irradiation in nude mice. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[20]  G. Viola,et al.  Induction of DNA‐Double‐Strand Breaks by Auger Electrons from 99mTc Complexes with DNA‐Binding Ligands , 2005, Chembiochem : a European journal of chemical biology.

[21]  G. Speit,et al.  The comet assay: a sensitive genotoxicity test for the detection of DNA damage. , 2005, Methods in molecular biology.

[22]  C. Streffer,et al.  Analysis of the Action of the Restriction Endonuclease AluI Using Three Different Comet Assay Protocols , 2004, Strahlentherapie und Onkologie.

[23]  G. Sutmann,et al.  Is Coulomb explosion a damaging mechanism for 125IUdR? , 2004, International journal of radiation biology.

[24]  C. Urani,et al.  Comet assay evaluation of DNA single- and double-strand breaks induction and repair in C3H10T1/2 cells , 2004, Cell Biology and Toxicology.

[25]  W. Knapp,et al.  External targets for the production of 211At--review and status of the target development at the Hannover cyclotron. , 2004, Zeitschrift fur medizinische Physik.

[26]  M. Zalutsky,et al.  In vitro cytotoxicity of (211)at-astatide and (131)I-iodide to glioma tumor cells expressing the sodium/iodide symporter. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[27]  U. Haberkorn,et al.  Enhanced iodide transport after transfer of the human sodium iodide symporter gene is associated with lack of retention and low absorbed dose , 2003, Gene Therapy.

[28]  J. Dumont,et al.  Anion selectivity by the sodium iodide symporter. , 2003, Endocrinology.

[29]  M. Zalutsky,et al.  Sodium-iodide symporter (NIS)-mediated accumulation of [(211)At]astatide in NIS-transfected human cancer cells. , 2002, Nuclear medicine and biology.

[30]  T. Petrich,et al.  Establishment of radioactive astatine and iodine uptake in cancer cell lines expressing the human sodium/iodide symporter , 2002, European Journal of Nuclear Medicine and Molecular Imaging.

[31]  P. Olive.  The comet assay. An overview of techniques. , 2002, Methods in molecular biology.

[32]  U. Haberkorn,et al.  Iodide uptake in human anaplastic thyroid carcinoma cells after transfer of the human thyroid peroxidase gene , 2001, European Journal of Nuclear Medicine.

[33]  L. Böhm,et al.  Comparison of cell inactivation by Auger electrons using the two reagents 4-[123I]iodoantipyrine and [123I]NaI , 2001, Radiation and environmental biophysics.

[34]  G. Ferro-Flores,et al.  Assessment of radiation-induced DNA damage caused by the incorporation of 99mTc-radiopharmaceuticals in murine lymphocytes using single cell gel electrophoresis. , 2000, Mutation research.

[35]  J. Roeske,et al.  Values of "S," , and <(z1)2> for dosimetry using alpha-particle emitters. , 1999, Medical physics.

[36]  J. Humm,et al.  Dosimetry of Auger-electron-emitting radionuclides: report no. 3 of AAPM Nuclear Medicine Task Group No. 6. , 1994, Medical physics.

[37]  M G Stabin,et al.  Absorbed fractions for electrons and beta particles in spheres of various sizes. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[38]  N. Singh,et al.  Modifications of alkaline microgel electrophoresis for sensitive detection of DNA damage. , 1994, International journal of radiation biology.

[39]  R. Howell,et al.  Radiation spectra for Auger-electron emitting radionuclides: report No. 2 of AAPM Nuclear Medicine Task Group No. 6. , 1992, Medical physics.

[40]  A. Wolf,et al.  The in vitro radiobiology of astatine-211 decay. , 1986, Radiation research.

[41]  S. Adelstein,et al.  A rapid and reproducible method for the separation of cells from radioactive media. , 1980, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[42]  S. Adelstein,et al.  5-125I-iododeoxyuridine as prototype for radionuclide therapy with Auger emitters , 1977, Nature.

[43]  S. Adelstein,et al.  The radiotoxicity of iodine-125 in mammalian cells II. A comparative study on cell survival and cytogenetic responses to 125IUdR, 131TUdR, and 3HTdR. , 1976, Radiation research.

[44]  L. Feinendegen.  Biological damage from the Auger effect, possible benefits , 1975, Radiation and environmental biophysics.