Assessment of radiation-induced DNA damage caused by the incorporation of -radiopharmaceuticals in murine lymphocytes using single cell gel electrophoresis

Pedraza-López, Martha; Ferro-Flores, Guillermina; Mendiola-Cruz, M.T.; Morales-Ramı́rez, P.

doi:10.1016/s1383-5718(99)00221-1

Cited by 18 publications

(11 citation statements)

References 12 publications

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“…Application of an electric field resolves fragmented DNA as a “tail” beyond the large, supercoiled, undamaged DNA “head” (Olive and Banath 1993). The comet assay has been useful to assess DNA damage caused by AEs (Haines et al 2001; Hoyes et al 2001; Olive and Banath 1993; Pedraza-López et al 2000; Piron et al 2014; Reske et al 2007). For example, the comet assay was used to show increased DNA damage caused by 99m Tc-hexamethylpropylenamineoxime (HMPAO) over 99m Tc gentisic acid when internalised into the cytoplasm or remaining bound to the cell membrane of lymphocytes, respectively (Pedraza-López et al 2000).…”

Section: Radiobiological Propertiesmentioning

confidence: 99%

Auger electrons for cancer therapy – a review

Facca

Cai

et al. 2019

EJNMMI radiopharm. chem.

266

207

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Background: Auger electrons (AEs) are very low energy electrons that are emitted by radionuclides that decay by electron capture (e.g. 111 In, 67 Ga, 99m Tc, 195m Pt, 125 I and 123 I). This energy is deposited over nanometre-micrometre distances, resulting in high linear energy transfer (LET) that is potent for causing lethal damage in cancer cells. Thus, AE-emitting radiotherapeutic agents have great potential for treatment of cancer. In this review, we describe the radiobiological properties of AEs, their radiation dosimetry, radiolabelling methods, and preclinical and clinical studies that have been performed to investigate AEs for cancer treatment. Results: AEs are most lethal to cancer cells when emitted near the cell nucleus and especially when incorporated into DNA (e.g. 125 I-IUdR). AEs cause DNA damage both directly and indirectly via water radiolysis. AEs can also kill targeted cancer cells by damaging the cell membrane, and kill non-targeted cells through a cross-dose or bystander effect. The radiation dosimetry of AEs considers both organ doses and cellular doses. The Medical Internal Radiation Dose (MIRD) schema may be applied. Radiolabelling methods for complexing AE-emitters to biomolecules (antibodies and peptides) and nanoparticles include radioiodination (125 I and 123 I) or radiometal chelation (111 In, 67 Ga, 99m Tc). Cancer cells exposed in vitro to AE-emitting radiotherapeutic agents exhibit decreased clonogenic survival correlated at least in part with unrepaired DNA double-strand breaks (DSBs) detected by immunofluorescence for γH2AX, and chromosomal aberrations. Preclinical studies of AE-emitting radiotherapeutic agents have shown strong tumour growth inhibition in vivo in tumour xenograft mouse models. Minimal normal tissue toxicity was found due to the restricted toxicity of AEs mostly on tumour cells targeted by the radiotherapeutic agents. Clinical studies of AEs for cancer treatment have been limited but some encouraging results were obtained in early studies using 111 In-DTPAoctreotide and 125 I-IUdR, in which tumour remissions were achieved in several patients at administered amounts that caused low normal tissue toxicity, as well as promising improvements in the survival of glioblastoma patients with 125 I-mAb 425, with minimal normal tissue toxicity. Conclusions: Proof-of-principle for AE radiotherapy of cancer has been shown preclinically, and clinically in a limited number of studies. The recent introduction of many biologically-targeted therapies for cancer creates new opportunities to design novel AE-emitting agents for cancer treatment. Pierre Auger did not conceive of the application of AEs for targeted cancer treatment, but this is a tremendously exciting future that we and many other scientists in this field envision.

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Section: Radiobiological Propertiesmentioning

confidence: 99%

Auger electrons for cancer therapy – a review

Facca

Cai

et al. 2019

EJNMMI radiopharm. chem.

266

207

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“…We found a D 37 in PC Cl3 cells of 2.3-2.8 Gy, whereas Kriehuber et al evaluated a D 37 of 13.2 Gy. Pedraza-Lopez et al (2000) investigated lymphocytes with 99m Tc-Exametazime (HMPAO) to obtain intracellular uptake and 99m Tc-gentisic acid that is bound to the cell surface. For both radiotracers, a higher DNA damage in relation to 99m Tc-pertechnetate was observed.…”

Section: Resultsmentioning

confidence: 99%

Reduction in clonogenic survival of sodium-iodide symporter (NIS)-positive cells following intracellular uptake of^99mTc versus¹⁸⁸Re

Freudenberg

Wendisch

Runge

et al. 2012

International Journal of Radiation Biology

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Uptake of (188)Re and (99m)Tc decreased cell survival. Intracellular (99m)Tc yielded a dose increase that was higher compared to (188)Re due to emitted Auger and internal conversion-electrons. Up to 5 Gy there was no difference in radiotoxicity of (188)Re and (99m)Tc. At doses higher than 5 Gy intracellular (99m)Tc became less radiotoxic than (188)Re, probably due to a non-uniform lognormal radionuclide uptake.

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“…Although the use of I‐125 would not be considered a suitable tracer for imaging patients because of the significant radiation dose associated with its use, technetium‐99m sodium pertechnetate delivers an effective radiation dose that is 100 times lower than that of I‐125. Furthermore, studies have shown that technetium‐99m in the form of sodium pertechnetate appears to have a low potential to induce DNA damage in cells . This fact, combined with the low effective dose from this radiotracer, makes it an ideal candidate imaging agent for serial studies in combination with the NIS reporter.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, studies have shown that technetium-99m in the form of sodium pertechnetate appears to have a low potential to induce DNA damage in cells. 61 This fact, combined with the low effective dose from this radiotracer, makes it an ideal candidate imaging agent for serial studies in combination with the NIS reporter. Another potential concern with repeated SPECT/CT imaging in these patients is the cumulative radiation exposure over time and the associated risks of radiation-induced cancer.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive 3‐dimensional imaging of liver regeneration in a mouse model of hereditary tyrosinemia type 1 using the sodium iodide symporter gene

et al. 2015

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4 Imanis Life Sciences, Rochester, MNCell transplantation is a potential treatment for the many liver disorders that are currently only curable by organ transplantation. However, one of the major limitations of hepatocyte (HC) transplantation is an inability to monitor cells longitudinally after injection. We hypothesized that the thyroidal sodium iodide symporter (NIS) gene could be used to visualize transplanted HCs in a rodent model of inherited liver disease: hereditary tyrosinemia type 1. Wild-type C57Bl/6J mouse HCs were transduced ex vivo with a lentiviral vector containing the mouse Slc5a5 (NIS) gene controlled by the thyroxine-binding globulin promoter. NIS-transduced cells could robustly concentrate radiolabeled iodine in vitro, with lentiviral transduction efficiencies greater than 80% achieved in the presence of dexamethasone. Next, NIS-transduced HCs were transplanted into congenic fumarylacetoacetate hydrolase knockout mice, and this resulted in the prevention of liver failure. NIStransduced HCs were readily imaged in vivo by single-photon emission computed tomography, and this demonstrated for the first time noninvasive 3-dimensional imaging of regenerating tissue in individual animals over time. We also tested the efficacy of primary HC spheroids engrafted in the liver. With the NIS reporter, robust spheroid engraftment and survival could be detected longitudinally after direct parenchymal injection, and this thereby demonstrated a novel strategy for HC transplantation. This work is the first to demonstrate the efficacy of NIS imaging in the field of HC transplantation. We anticipate that NIS labeling will allow noninvasive and longitudinal identification of HCs and stem cells in future studies related to liver regeneration in small and large preclinical animal models. Liver Transpl 21:442-453, 2015. V C 2015 AASLD.

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Assessment of radiation-induced DNA damage caused by the incorporation of -radiopharmaceuticals in murine lymphocytes using single cell gel electrophoresis

Cited by 18 publications

References 12 publications

Auger electrons for cancer therapy – a review

Auger electrons for cancer therapy – a review

Reduction in clonogenic survival of sodium-iodide symporter (NIS)-positive cells following intracellular uptake of^99mTc versus¹⁸⁸Re

Noninvasive 3‐dimensional imaging of liver regeneration in a mouse model of hereditary tyrosinemia type 1 using the sodium iodide symporter gene

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Assessment of radiation-induced DNA damage caused by the incorporation of -radiopharmaceuticals in murine lymphocytes using single cell gel electrophoresis

Cited by 18 publications

References 12 publications

Auger electrons for cancer therapy – a review

Auger electrons for cancer therapy – a review

Reduction in clonogenic survival of sodium-iodide symporter (NIS)-positive cells following intracellular uptake of99mTc versus188Re

Noninvasive 3‐dimensional imaging of liver regeneration in a mouse model of hereditary tyrosinemia type 1 using the sodium iodide symporter gene

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Reduction in clonogenic survival of sodium-iodide symporter (NIS)-positive cells following intracellular uptake of^99mTc versus¹⁸⁸Re