Radiation induced DNA double strand breaks undergoing PET/CT examinations. Poster No.: C-1685 Congress: ECR 2011 Type: Scientific Exhibit Authors: M. S. May, M. Brand, T. Löwe, M. Sommer, C. Engert, U. Kahl, O. Prante, M. Uder, M. A. Kuefner; Erlangen/DE Keywords: DOI: Nuclear medicine, Research, Radioprotection, PET-CT, Experimental, Radiobiology, Laboratory tests, Radiation effects, Blood, Neoplasia 10.1594/ecr2011/C-1685 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myesr.org Page 1 of 9
Purpose Background: Physical or mathematical dosimetry approaches in clinical routine can not include a measure of biological x-ray interactions. In patients undergoing combined positron emission tomography (PET) and computed tomography (CT) contribution of internal and external radiation exposure is complex. #-H2AX immunoflourescence microscopy is a validated method for determination of radiation induced DNA double-strand breaks (DSBs) Purpose: Measurement of induction and repair of DNA DSBs after 18- flourdeoxyglucose (FDG) administration Evaluation of biological x-ray damage during whole body CT exposure Differentiation between DNA lesions induced by FDG and CT Methods and Materials 20 Patients Sex: 16 male, 4 female Median age: 62 ± 14 years Median body mass index: 26 ± 5 kg/m PET: Body weight adapted injection protocol for FDG: 3 MBq/kg Median delay after FDG administration: 86 ± 20 min CT: Whole body scan range on a 64-slice scanner including: Brain - Neck - Thorax - Abdomen - Pelvis - Upper legs Tube voltage: 120 kv Attenuation (anatomy) based tube current modulation: 170 ref. mas Determination of DSBs: Page 2 of 9
Blood samples obtained before, at various points after FDG application and up to 24 hours after the CT scan Quantification of foci in isolated blood lymphocytes (figure 1) using fluorescence microscopy after staining against the phosphorylated histone variant #H2AX. Calculation of excess foci representing radiation induced DSBs by subtracting pre-exposure from corresponding post-exposure values Calculation of radiation dose to the blood (figure 2) by relating in-vivo DSB levels to values of standardized, individual in-vitro irradiations (50 mgy). Images for this section: Fig. 1: DSB quantification: After staining against the phosphorylated histone variant #H2AX every focus represents one DSB at fluorescence microscopy Page 3 of 9
Fig. 2: Radiation dose to blood is calculated by relating in-vivo DSB levels to values of aditionally performed, standardized in vitro-irradiations (50 mgy). Page 4 of 9
Results DSB values rise to a peak at 30 minutes after FDG administration, thereafter clearly decrease until the CT examination (figure 1). Whole body CT induces peak DSB values 5 minutes after exposure (figure 1). 24 hours after FDG-PET/CT baseline level is approximately attained. Excess foci representing radiation induced DSBs (figure 2): FDG: 0.16 ± 0.06 DSBs/cell CT: 0.17 ± 0.09 DSBs/cell Total radiation dose to blood consisted of approximately equal parts of FDG and whole body CT exposure (figure 3). Images for this section: Fig. 1: Individual exemplary DSB-time course for patient with interpolation line. FDG was injected at 0 minutes, whole body CT scan was performed at 75 minutes. Page 5 of 9
Fig. 2: Boxplots demonstrating absolute DSB levels at different time points: before and 30 minutes after FDG application (FDG), before CT scan (Before CT), 5 minutes after CT (CT) and after 24 hours (Boxes show interquartile ranges, the middle horizontal line represents the median, and the error bars indicate the range of the non-outlying data point). Page 6 of 9
Fig. 3: Boxplots demonstrating radiation dose to blood for PET and CT scan separately and for total exposure during FDG-PET/CT (Boxes show interquartile ranges, the middle horizontal line represents the median, and the error bars indicate the range of the nonoutlying data points). Page 7 of 9
Conclusion In all patients DNA DSBs are induced both by FDG-application as well as CT scans. Bio-distribution and repairing mechanisms account for a peak of FDGinduced DSBs after 30 minutes. FDG and whole body CT contribute in approximately equal parts to the total DSB induction and radiation dose to blood. DSBs are nearly completely repaired within 24 hours after exposure. References Grudzenski S, Kuefner MA, Heckmann MB, et al. (2009) Contrast mediumenhanced radiation damage caused by CT examinations. Radiology, 253(3):706-714 Kuefner MA, Grudzenski S, Hamann J, et al (2009) Effect of CT scan protocols on x-ray-induced DNA double-strand breaks in blood lymphocytes of patients undergoing coronary CT angiography. Eur Radiol, 20(12):2917-2924 Kuefner MA, Grudzenski S, Schwab SA, et al. (2009) [X-ray-induced DNA double-strand breaks after angiographic examinations of different anatomic regions]. Rofo, 181(4):374-380 Kuefner MA, Grudzenski S, Schwab SA, et al. (2009) DNA double-strand breaks and their repair in blood lymphocytes of patients undergoing angiographic procedures. Invest Radiol, 44(8):440-446 Kuefner MA, Hinkmann FM, Alibek S, et al. (2010) Reduction of X-ray induced DNA double-strand breaks in blood lymphocytes during coronary CT angiography using high-pitch spiral data acquisition with prospective ECG-triggering. Invest Radiol, 45(4):182-187 Lobrich M, Rief N, Kuhne M, et al. (2005) In vivo formation and repair of DNA double-strand breaks after computed tomography examinations. Proc Natl Acad Sci U S A, 102(25):8984-8989 Rothkamm K, Lobrich M (2003) Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses. Proc Natl Acad Sci U S A, 100(9):5057-5062 Personal Information Matthias S. May Page 8 of 9
Assistenzarzt / Resident Radiologisches Institut Maximiliansplatz 1 91054 Erlangen Phone: + 49 9131 8535571 Fax: +49 9131 8536068 E-mail: matthias.may@uk-erlangen.de Page 9 of 9