Quantification of DNA damage in patients undergoing non-contrast and contrast enhanced whole body PET/CT investigations using comet assay and micronucleus assay

Nautiyal, Amit; Mondal, Tanmoy; Mukherjee, Anirban; Mitra, Deepanjan; Kaushik, Aruna; Goel, Harish Chandra; Goel, Alpana; Dey, Subrata Kumar

doi:10.1080/09553002.2019.1577569

Cited by 7 publications

(10 citation statements)

References 38 publications

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“…They did not investigate the dose-dependency of the induced DNA damage either, but focused on the difference between a patient group that received a contrast agent and a corresponding non-contrast group. As a result, they report a significant increase in DNA damage in the contrast group compared to the non-contrast group [20], which is in accordance with the observations made in the present ex vivo study.…”

Section: Discussionsupporting

confidence: 92%

“…In a recent study, Nautiyal et al investigated the effect of ionizing radiation in patients undergoing non-contrast and contrast-enhanced [ 18 F]FDG PET/CT examinations using both comet assay and micronucleus assay [20]. They did not investigate the dose-dependency of the induced DNA damage either, but focused on the difference between a patient group that received a contrast agent and a corresponding non-contrast group.…”

Section: Discussionmentioning

confidence: 99%

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DNA Damage in Blood Leukocytes of Prostate Cancer Patients Undergoing PET/CT Examinations with [68Ga]Ga-PSMA I&T

Schumann

Scherthan

Frank

et al. 2020

Cancers

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The aim was to investigate the induction and repair of radiation-induced DNA double-strand breaks (DSBs) as a function of the absorbed dose to the blood of patients undergoing PET/CT examinations with [68Ga]Ga-PSMA. Blood samples were collected from 15 patients before and at four time points after [68Ga]Ga-PSMA administration, both before and after the PET/CT scan. Absorbed doses to the blood were calculated. In addition, blood samples with/without contrast agent from five volunteers were irradiated ex vivo by CT while measuring the absorbed dose. Leukocytes were isolated, fixed, and stained for co-localizing γ-H2AX+53BP1 DSB foci that were enumerated manually. In vivo, a significant increase in γ-H2AX+53BP1 foci compared to baseline was observed at all time points after administration, although the absorbed dose to the blood by 68Ga was below 4 mGy. Ex vivo, the increase in radiation-induced foci depended on the absorbed dose and the presence of contrast agent, which could have caused a dose enhancement. The CT-dose contribution for the patients was estimated at about 12 mGy using the ex vivo calibration. The additional number of DSB foci induced by CT, however, was comparable to the one induced by 68Ga. The significantly increased foci numbers after [68Ga]Ga-PSMA administration may suggest a possible low-dose hypersensitivity.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

DNA Damage in Blood Leukocytes of Prostate Cancer Patients Undergoing PET/CT Examinations with [68Ga]Ga-PSMA I&T

Schumann

Scherthan

Frank

et al. 2020

Cancers

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“…Patients were positioned inside the scanner for contrast-enhanced WB PET/CT examination, and were injected with Iohexol, Omnipaque 300 based on the patient body weight at dose of 84.57 ± 16.69 ml and flow rate of 2–4 ml/s (GE Healthcare; Shanghai co., Ltd. Shanghai, China) [ 24 ]. A scout scan (in which the patient first undergoes an ‘overview’ or ‘scout’ scan procedure during which X-ray projection data are obtained to identify the axial extent of the CT and PET study), breath-holding lung CT, WB CT and PET (from head to mid-thigh) and low-dose cine CT (provides cross-sectional millisecond tomography that is used for the correction of motion due to diaphragmatic movement) were obtained in an arms-up position and the imaging parameters for WB CT were followed according to our previous study [ 22 ]. After completion of CT, the attenuated corrected emission images were acquired for 2 min per bed position in a 3-dimensional mode for a total acquisition time of approximately 15–20 mins.…”

Section: Methodsmentioning

confidence: 99%

“…Our previous study observed that 18 F-FDG induced DSBs formation in isolated peripheral blood lymphocytes and chromosomal aberrations in a V79 cell line [ 20 , 21 ]. We also observed DNA breaks by comet and micronucleus assay after exposure to PET/CT procedure [ 22 ]. In the present study, we extended that work through quantifying the DSBs formation in patients’ blood samples by γ-H2AX assay, and assessed the total DNA RNA oxidative damage burden by quantifying urinary 8-hydroxy-2′-deoxyguanosine (from DNA), 8-hydroxyguanosine (from RNA) and 8-hydroxyguanine (DNA and RNA) levels.…”

Section: Introductionmentioning

confidence: 99%

An evaluation of DNA double strand break formation and excreted guanine species post whole body PET/CT procedure

Mondal

Nautiyal

Ghosh

et al. 2021

Journal of Radiation Research

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Ionizing radiation-induced oxidation and formation of deoxyribonucleic acid (DNA) double strand breaks (DSBs) are considered the exemplar of genetic lesions. Guanine bases are most prone to be oxidized when DNA and Ribonucleic acid (RNA) are damaged. The repair processes that are initiated to correct this damage release multiple oxidized guanine species into the urine. Hence, the excretion of guanine species can be related with the total repair process. Our study quantified the total DSBs formation and the amount of guanine species in urine to understand the DNA break and repair process after whole body (WB) exposure to 18F-FDG positron emission tomography/computed tomography (PET/CT). A total of 37 human participants were included with control and test groups and the average radiation dose was 27.50 ± 2.91 mSv. γ-H2AX foci assay in the collected blood samples was performed to assess the DSBs, and excreted guanine species in urine were analyzed by a competitive ELISA method. We observed a significant increase of DNA damage that correlated well with the increasing dose (p-value 0.009) and body weight (p-value 0.05). In the test group, excreted guanine species in urine sample significantly increased (from 24.29 ± 5.82 to 33.66 ± 7.20 mg/mmol creatinine). A minimum (r2 = 0.0488) correlation was observed between DSBs formation and excreted guanine species. A significant difference of DNA damage and 8-OHdG formation was seen in the test group compared to controls. Larger population studies are needed to confirm these observations, describe the fine-scale timing of changes in the biomarker levels after exposure, and further clarify any potential risks to patients from PET/CT procedures.

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“…In diagnostic nuclear medicine applications, especially in longitudinal procedures, the role of radiobiology and the longterm consequences of radiobiology-related findings, such as reported in studies on DNA damage and repair, still has to be defined [95][96][97][98][99][100][101]. Currently, these studies provide no evidence that diagnostic nuclear medicine procedures are not safe.…”

Section: Position Of the Eanmmentioning

confidence: 99%

EANM position paper on the role of radiobiology in nuclear medicine

Aerts

Eberlein

Holm

et al. 2021

Eur J Nucl Med Mol Imaging

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Executive SummaryWith an increasing variety of radiopharmaceuticals for diagnostic or therapeutic nuclear medicine as valuable diagnostic or treatment option, radiobiology plays an important role in supporting optimizations. This comprises particularly safety and efficacy of radionuclide therapies, specifically tailored to each patient. As absorbed dose rates and absorbed dose distributions in space and time are very different between external irradiation and systemic radionuclide exposure, distinct radiation-induced biological responses are expected in nuclear medicine, which need to be explored. This calls for a dedicated nuclear medicine radiobiology. Radiobiology findings and absorbed dose measurements will enable an improved estimation and prediction of efficacy and adverse effects. Moreover, a better understanding on the fundamental biological mechanisms underlying tumor and normal tissue responses will help to identify predictive and prognostic biomarkers as well as biomarkers for treatment follow-up. In addition, radiobiology can form the basis for the development of radiosensitizing strategies and radioprotectant agents. Thus, EANM believes that, beyond in vitro and preclinical evaluations, radiobiology will bring important added value to clinical studies and to clinical teams. Therefore, EANM strongly supports active collaboration between radiochemists, radiopharmacists, radiobiologists, medical physicists, and physicians to foster research toward precision nuclear medicine.

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Quantification of DNA damage in patients undergoing non-contrast and contrast enhanced whole body PET/CT investigations using comet assay and micronucleus assay

Abstract: Total 84 patients were included in this study out of which 50 were males and 34 were females. During overall comparison between males and females, no significant difference was noted in DNA damage parameters: Comet TM and MNBC%.

Cited by 7 publications

References 38 publications

DNA Damage in Blood Leukocytes of Prostate Cancer Patients Undergoing PET/CT Examinations with [68Ga]Ga-PSMA I&T

DNA Damage in Blood Leukocytes of Prostate Cancer Patients Undergoing PET/CT Examinations with [68Ga]Ga-PSMA I&T

An evaluation of DNA double strand break formation and excreted guanine species post whole body PET/CT procedure

EANM position paper on the role of radiobiology in nuclear medicine

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