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].