On the dose calculation at the cellular level and its implications for the RBE of {sup 99m}Tc and {sup 123}I

Journal Article · Sun Jun 15 04:00:00 EDT 2014 · Medical Physics

DOI:https://doi.org/10.1118/1.4876296· OSTI ID:22412504

Runge, R.; Maucksch, U.; Berger, V.; Kotzerke, J. ^[1]

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1. University Hospital/Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Department of Nuclear Medicine, Dresden, Saxony 01307 (Germany)

Purpose: Based on the authors’ previous findings concerning the radiotoxicity of{sup 99m}Tc, the authors compared the cellular survival under the influence of this nuclide with that following exposure to the Auger electron emitter {sup 123}I. To evaluate the relative biological effectiveness (RBE) of both radionuclides, knowledge of the absorbed dose is essential. Thus, the authors present the dose calculations and discuss the results based on different models of the radionuclide distribution. Both different target volumes and the influence of the uptake kinetics were considered. Methods: Rat thyroid PC Cl3 cells in culture were incubated with either{sup 99m}Tc or {sup 123}I or were irradiated using 200 kV x-rays in the presence or absence of perchlorate. The clonogenic cell survival was measured via colony formation. In addition, the intracellular radionuclide uptake was quantified. Single-cell dose calculations were based on Monte Carlo simulations performed using Geant4. Results: Compared with external radiation using x-rays (D{sub 37} = 2.6 Gy), the radionuclides {sup 99m}Tc (D{sub 37} = 3.5 Gy), and {sup 123}I (D{sub 37} = 3.8 Gy) were less toxic in the presence of perchlorate. In the absence of perchlorate, the amount of activity a{sub 37} that was necessary to reduce the surviving fraction (SF) to 0.37 was 22.8 times lower for {sup 99m}Tc and 12.4 times lower for {sup 123}I because of the dose increase caused by intracellular radionuclide accumulation. When the cell nucleus was considered as the target for the dose calculation, the authors found a RBE of 2.18 for {sup 99m}Tc and RBE = 3.43 for {sup 123}I. Meanwhile, regarding the dose to the entire cell, RBE = 0.75 for {sup 99m}Tc and RBE = 1.87 for {sup 123}I. The dose to the entire cell was chosen as the dose criterion because of the intracellular radionuclide accumulation, which was found to occur solely in the cytoplasm. The calculated number of intracellular decays per cell was (975 ± 109) decays/MBq for {sup 99m}Tc and (221 ± 82) decays/MBq for {sup 123}I. Conclusions: The authors’ data indicate that extra-nuclear targets to Auger electrons exist, which is obvious from our dose calculations. When considering the dose to the cell nucleus, the authors found an enhanced RBE for{sup 99m}Tc and {sup 123}I relative to acute x-ray irradiation and pure extracellular irradiation with both radionuclides. Surprisingly, the authors did not find any radionuclide accumulation in the cell nucleus, indicating that there are additional radiosensitive targets besides the DNA. In addition, the authors demonstrated the necessity of cellular dose calculations in radiobiological experiments using unsealed radionuclides and identified the relevant parameters.

• OSTI ID: 22412504
• Journal Information: Medical Physics, Journal Name: Medical Physics Journal Issue: 6 Vol. 41; ISSN 0094-2405; ISSN MPHYA6
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ABSORBED RADIATION DOSES
CELL NUCLEI
COLONY FORMATION
COMPUTERIZED SIMULATION
CYTOPLASM
IODINE 123
MONTE CARLO METHOD
PERCHLORATES
RADIONUCLIDE KINETICS
RBE
TECHNETIUM 99
TOXICITY
UPTAKE