Deoxyribonucleic acid damage-associated biomarkers of ionising radiation: current status and future relevance for radiology and radiotherapy

Manning, Grainne; Rothkamm, Kai

doi:10.1259/bjr.20130173

Cited by 22 publications

(17 citation statements)

References 109 publications

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“…In general, DSBs evoke a DNA damage response during which the DSB signal is amplified and several repair routes are induced involving proteins that can serve as biomarkers (4).…”

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confidence: 99%

DNA Damage in Peripheral Blood Lymphocytes of Thyroid Cancer Patients After Radioiodine Therapy

et al. 2015

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The aim of the study was to investigate DNA double-strand break (DSB) formation and its correlation to the absorbed dose to the blood in patients with surgically treated differentiated thyroid cancer undergoing their first radioiodine therapy for remnant ablation. Methods: Twenty patients were included in this study. At least 7 peripheral blood samples were obtained before and between 0.5 and 120 h after administration of radioiodine. From the timeactivity curves of the blood and the whole body, residence times for the blood self-irradiation and the irradiation from the whole body were determined. Peripheral blood lymphocytes were isolated, ethanol-fixed, and subjected to immunofluorescence staining for colocalizing γ-H2AX/53BP1 DSB-marking foci. The average number of DSB foci per cell per patient sample was analyzed as a function of the absorbed dose to the blood and compared with an in vitro calibration curve for 131 I and 177 Lu established previously in our institution. Results: The average number of radiation-induced foci (RIF) per cell increased over the first 3 h after radionuclide administration and decreased thereafter. A linear fit from 0 to 2 h as a function of the absorbed dose to the blood agreed with our in vitro calibration curve. At later time points, RIF numbers diminished, along with dropping dose rates, indicating progression of DNA repair. Individual patient data were characterized by a linear dosedependent increase and a biexponential response function describing a fast and a slow repair component. Conclusion: With the experimental results and model calculations presented in this work, a dose-response relationship is demonstrated, and an analytic function describing the time course of the in vivo damage response after internal irradiation of patients with 131 I is established.Key Words: γ-H2AX; 53BP1; biological dosimetry; radioiodine therapy; DTC; absorbed dose to blood; dose response; DSB focus assay; DNA damage; 131 I; differentiated thyroid cancer Nucl Med 2016; 57:173-179 DOI: 10.2967/jnumed.115.164814 Af ter total thyroidectomy for differentiated thyroid cancer (DTC), patients generally receive one or more treatments with high activities of 131 I. The purpose of the initial radioiodine therapy after surgery is to ablate remnant thyroid tissue and to effectively treat any iodine-avid metastases (1,2). Because patients with DTC generally do not undergo chemotherapy or other radiotherapy before radioiodine therapy, this patient group is ideally suited for the investigation of the DNA damage in blood lymphocytes induced by protracted, nearly homogeneous whole-body irradiation. In this setting, all organs, including the blood, are irradiated by b-particles emitted from circulating 131 I and from penetrating g-radiation originating from activity dispersed throughout the body. The absorbed dose and dose rate to the blood is assessed by defining the timeactivity curves in the blood and the whole body, integrating the corresponding time-activity curves and calculating the absorbed dose acco...

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“…In general, DSBs evoke a DNA damage response during which the DSB signal is amplified and several repair routes are induced involving proteins that can serve as biomarkers (4).…”

mentioning

confidence: 99%

DNA Damage in Peripheral Blood Lymphocytes of Thyroid Cancer Patients After Radioiodine Therapy

et al. 2015

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“…Therefore, a common side effect observed in cancer patients undergoing chemotherapy or radiotherapy is bone marrow depletion. [30] A potential additional application of our liposomes is to deliver drugs that can protect bone marrow from destruction or help aid in the recovery of bone marrow at much higher concentrations than what can be achieved by systemic delivery of naked drugs. [31] The bone marrow liposome's long stability (Figure S5) and near 100% labeling efficiency (Figure S2) enable us to develop a kit ready for immediate use with adjustment of pH, labeling of PET radiotracer, and neutralization.…”

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confidence: 99%

Copper-64 labeled liposomes for imaging bone marrow

Lee

Gangangari

Kalidindi

et al. 2016

Nuclear Medicine and Biology

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Introduction Bone marrow is the soft tissue compartment inside the bones made up of hematopoietic cells, adipocytes, stromal cells, phagocytic cells, stem cells, and sinusoids. While [18F]-FLT has been utilized to image proliferative marrow, to date, there are no reports of particle based positron emission tomography (PET) imaging agents for imaging bone marrow. We have developed copper-64 labeled liposomal formulation that selectively targets bone marrow and therefore serves as an efficient PET probe for imaging bone marrow. Methods Optimized liposomal formulations were prepared with succinyl PE, DSPC, cholesterol, and mPEG-DSPE (69:39:1:10:0.1) with diameters of 90 and 140 nm, and were doped with DOTA-Bn-DSPE for stable 64Cu incorporation into liposomes. Results PET imaging and biodistribution studies with 64Cu-labeled liposomes indicate that accumulation in bone marrow was as high as 15.18 ± 3.69 %ID/g for 90 nm liposomes and 7.01 ± 0.92 %ID/g for 140 nm liposomes at 24 h post-administration. In vivo biodistribution studies in tumor-bearing mice indicate that the uptake of 90 nm particles is approximately 0.89 ± 0.48 %ID/g in tumor and 14.22 ± 8.07 %ID/g in bone marrow, but respective values for Doxil® like liposomes are 0.83 ± 0.49 %ID/g and 2.23 ± 1.00 %ID/g. Conclusion Our results indicate that our novel PET labeled liposomes target bone marrow with very high efficiency and therefore can function as efficient bone marrow imaging agents.

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“…We compared our findings with a previously used gene in GE biodosimetry, FDXR (Boldt et al 2012;Kabacik et al 2011;Knops et al 2012;Manning and Rothkamm;Paul and Amundson, 2008), which is regulated by p53 family and with our previous in vitro study (Khodamoradi et al In Press). In our pervious study, we found the dose response curve of the FDXR and RAD51 genes in response to different doses and 6 and 18 MV beam energies in human PBLs.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Biodosimetry: Quantitative Assessment of Radiation Dose with Total Body Exposure of Rats

Saberi

Khodamoradi²,

Birgani³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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Background: Accurate dose assessment and correct identification of irradiated from non-irradiated people are goals of biological dosimetry in radiation accidents. Objectives: Changes in the FDXR and the RAD51 gene expression (GE) levels were here analyzed in response to total body exposure (TBE) to a 6 MV x-ray beam in rats. We determined the accuracy for absolute quantification of GE to predict the dose at 24 hours. Materials and Methods: For this in vivo experimental study, using simple randomized sampling, peripheral blood samples were collected from a total of 20 Wistar rats at 24 hours following exposure of total body to 6 MV X-ray beam energy with doses (0.2, 0.5, 2 and 4 Gy) for TBE in Linac Varian 2100C/D (Varian, USA) in Golestan Hospital, in Ahvaz, Iran. Also, 9 rats was irradiated with a 6MV X-ray beam at doses of 1, 2, 3 Gy in 6MV energy as a validation group. A sham group was also included. After RNA extraction and DNA synthesis, GE changes were measured by the QRT-PCR technique and an absolute quantification strategy by taqman methodology in peripheral blood from rats. ROC analysis was used to distinguish irradiated from non-irradiated samples (qualitative dose assessment) at a dose of 2 Gy. Results: The best fits for mean of responses were polynomial equations with a R2 of 0.98 and 0.90 (for FDXR and RAD51 dose response curves, respectively). Dose response of the FDXR gene produced a better mean dose estimation of irradiated "validation" samples compared to the RAD51 gene at doses of 1, 2 and 3 Gy. FDXR gene expression separated the irradiated rats from controls with a sensitivity, specificity and accuracy of 87.5%, 83.5% and 81.3%, respectively, 24 hours after dose of 2 Gy. These values were significantly (p<0.05) higher than the 75%, 75% and 75%, respectively, obtained using gene expression of RAD51 analysis at a dose of 2 Gy. Conclusions: Collectively, these data suggest that absolute quantification by gel purified quantitative RT-PCR can be used to measure the mRNA copies for GE biodosimetry studies at comparable accuracy to similar methods. In the case of TBE with 6MV energy, FDXR gene expression analysis is more precise than that with RAD51 for quantitative and qualitative dose assessment.

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Deoxyribonucleic acid damage-associated biomarkers of ionising radiation: current status and future relevance for radiology and radiotherapy

Cited by 22 publications

References 109 publications

DNA Damage in Peripheral Blood Lymphocytes of Thyroid Cancer Patients After Radioiodine Therapy

DNA Damage in Peripheral Blood Lymphocytes of Thyroid Cancer Patients After Radioiodine Therapy

Copper-64 labeled liposomes for imaging bone marrow

Gene Expression Biodosimetry: Quantitative Assessment of Radiation Dose with Total Body Exposure of Rats

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