Adress: Work: Yeşilhisar State Hospital, Department of Pediatrics, Kayseri, Turkey
E-mail: drselcukvarol@gmail.com
THE IMPACT OF TC-99M DMSA SCINTIGRAPHY
ON DNA DAMAGE AND OXIDATIVE STRESS IN CHILDREN
Abstract
Background: Tc-99m DMSA scintigraphy is a commonly used imaging modality in the pediatric population. The radiopharmaceuticals which have the effects of ionizing are used in this method. This study aimed to investigate the impact of the Tc-99m DMSA scan on renal oxidative stress and mononuclear leukocyte DNA damage.
Methods: Twenty-seven patients who performed Tc-99m DMSA scintigraphy were included in this study. Three ml heparinized blood samples were taken just before, during, and after a week from the scintigraphy. Mononuclear leukocyte(MNL) DNA damage, total antioxidant status (TAS), and total oxidant status(TOS) were measured in blood samples. The oxidative stress index (OSI) was calculated. The spot urine samples were taken from each patient before and within three days after performing the scintigraphy. TAS/Creatinine(TAS/Cr), TOS/Creatinin(TOS/Cr), and N-acetyl-glucosaminidase/creatinine(NAG/Cr) levels were measured in urine samples. OSI was calculated.
Results: There was no statistically significant difference in the values of TAS, TOS and OSI studied in serum samples between controls and study group(p=0.105, p=0.913, and p=0.721, respectively). There was no statistically significant difference in the levels of TAS/Cr, TOS/Cr, NAG/Cr, and OSI which were studied in urine samples before and after scintigraphy scan(p=0.381, p=0.543, p=0.129 and p=0.08 respectively). The levels of DNA damage were increased only after the performance of the scintigraphy scan and decreased a week later(p<0.05).
Conclusions: The effect of Tc-99m DMSA scintigraphy is insufficient to create oxidative damage, but it can cause DNA damage via the direct impact of ionizing radiation which can be repaired again in a short time.
Keywords: Tc-99m DMSA, DNA damage; reactive oxygen species; renal tubular injury; children
Static renal scans using the radioisotope Tc-99m DMSA provide visualization of focal renal parenchymal abnormalities, assessment of a difference in kidney function and detection of renal scars. This scan has considerable amount of radiation.
In our study we showed that Tc-99m DMSA scan doesn’t create oxidative stress but by analyzing mononuclear DNA damage we demonstrated that it can cause DNA damage via ionizing radiation which can be repaired in a short time
Introduction
The use of diagnostic radiologic imaging has increased over the last decades, especially computed tomography (CT) and nuclear medicine technology [1]. These procedures deliver high dose of radiation and epidemiologically linked with radiation-induced cancers [2]. Also, there is an emerging evidence that early life diagnostic radiation exposure is associated with childhood malignancies [3, 4]. Free radicals induced by ionizing radiation (such as superoxide, hydrogen peroxide and hydroxyl radicals) react with macromolecules, impair oxidant-antioxidant balance over time and lead to the development of oxidative stress [5] Oxidative stress is described as the disruption of the balance between free radical production and antioxidant levels in favor of free radicals. This causes molecular damage, which accumulates over time in tissues and cells. DNA damage can lead to mutations, an essential step in carcinogenesis [6]. It is estimated that 2% of future cancers will result from current diagnostic imaging use [2].
The diagnostic nuclear medicine procedures that are widely used in the pediatric population are Technetium-99m-dimercapto succinic acid (Tc-99m DMSA), Technetium-99-m-diethylenetriamine pentaacetic acid (Tc-99m DTPA) and, Technetium-99m-mercaptoacetyltriglycine (Tc-99m MAG-3) (7). DMSA plays an essential role in the assessment of renal scars in febrile urinary tract infections and differential function of kidneys. Vesicoureteral reflux along with recurrent urinary tract infections are important risk factors for renal damage [8]. The cortical uptake decrease on DMSA is considered as a marker of upper urinary tract infection and an indirect indicator of vesicoureteral reflux and renal scarring [9]. DMSA imaging involves the intravenous administration of radiolabeled tracer that binds to proximal convoluted tubules. The radiation dose delivered from the procedure changes from one institution to another. Michaud et al. demonstrated that the mean cumulative radiation dose of DMSA scan per patient approach to those of pediatric chest computed tomography [10].
Compared to adults, nationwide survey data on radiation-induced risks are limited in pediatric population. The radiation-related harmful effects of DMSA scan is not well known. Salmanoglu E et al. showed impaired oxidative and nitrosative balance in adult patients who undergone DMSA scintigraphy. Malondialdehyde which is an oxidative stress biomarker, was significantly increased in patient group compared to controls [11]. Up to our knowledge, there is no study performed in pediatric population investigating the oxidative stress and DNA damage of DMSA scan. Also, there is no study on possible tubular injury of the radiopharmaceutical used for the scan. N-acetyl-beta-D-glucosaminidase (NAG) is a lysosomal enzyme found in many tissues and, is a widely used urinary biomarker for the diagnosis of renal tubular injury [12]. Urinary NAG is used to detect renal tubular damage in cases such as acute pyelonephritis, vesicoureteral reflux, hydronephrosis, nephrotoxic drug or heavy metal exposure, nephrolithiasis, proteinuria, hyperglycemia and, hypertension [13].
This study aimed to determine the possible harmful effects and cellular damage of Tc-99m DMSA scintigraphy in the pediatric population by determining radiation-induced renal oxidative stress and mononuclear leukocyte (MNL) DNA damage, and renal tubular injury by urine NAG level measurements.
Methods
This prospective cohort study involved 27 pediatric patients who were followed up at the outpatient pediatric nephrology clinic and Tc-99m dimercapto- succinic acid (DMSA) scintigraphy was planned between April 2015-January 2016. The indications were recurrent urinary tract infections and detection of renal scars with the suspicion of vesicoureteral reflux. Patients with nephrolithiasis, history of premature birth, and who had recent urinary tract infection six month prior to scintigraphy or used antibiotics in last one month were excluded from the study. Power calculation was done with the Gpower analysis [14]. A previous study with Tc-99m pertechnetate thyroid scintigraphy was used and a calculation with the data of mean and standard deviation of dependent variables (92.06+ 13.38 and 79+ 9.43) was performed [15]. As a result of the Gpower analysis, the effect size was found to be 0.8. The determined study sample size was 23 if confidence level was 95%, power was 95%, and the effect size was 0.8. We included 27 patients with the probability of 20% missing patient.
DMSA scans were performed on a dual-head gamma camera (Symbia E, Siemens Medical Solutions, Hoffman Estates, IL, USA) with a low-energy high-resolution collimator. Images were acquired with anterior-posterior, lateral and oblique projections in 128x128 matrix, 300.000 counts or 5 minutes per image. In our institution, an intravenous hydration, bladder Foley catheter or sedation were not routinely applied for DMSA scans. Oral hydration was encouraged. Images were acquired 2 to 3 hours after radiotracer injection. Late images were taken as needed. For the pediatric population, an activity of 1.85 MBq/kg (0.05 mCi/kg) Tc-99m-DMSA was injected, and the minimum administered activity was 18.5 MBq (0.5 mCi) [16].