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1.
Nucl Med Commun ; 40(10): 995-1000, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31365496

ABSTRACT

OBJECTIVE: Our purpose was to establish a simple and feasible method for monitoring and controlling the Tc-Technegas inhaled to improve the success ratio of imaging and ensure the imaging quality. MATERIALS AND METHODS: The relationship between the success ratio and the pulmonary ventilation counting rate (VCR) of 113 cases, the activity of perfusion imaging agents injected and the pulmonary perfusion counting rate (PCR) of another 114 cases were analysed retrospectively. And combined with the relationship between the surface radioactivity monitoring value and the SPECT probe counting rate of a pulmonary model, the effective range of the VCR and the surface radioactivity monitoring value were determined. Two hundred fifty cases with Tc-Technegas inhaled monitored and controlled were used to verify the reliability and practicability of this method. RESULTS: The VCR of the ventilation/perfusion imaging with deep venous thrombosis imaging and the ventilation/perfusion imaging without deep venous thrombosis imaging was in 1.0-3.0 kct/s and 1.0-2.0 kct/s when the monitoring values of handheld radiation monitor was within the range of 60-170 µSv/h and 60-110 µSv/h, respectively. The success ratio of the V/Q-Only increased from 48.9% (43/88) of the control group to 80.8% (122/151) of the experimental group. The VCR in the two groups was examined by the non-parametric Mann-Whitney U test (P < 0.001), which indicated that there was a significant difference between the experimental group and the control group. CONCLUSION: The external monitoring method established in this study was of great significance in improving the success ratio of 1-day pulmonary ventilation/perfusion imaging and ensuring the image quality.


Subject(s)
Inhalation , Perfusion Imaging/adverse effects , Pulmonary Ventilation , Sodium Pertechnetate Tc 99m/administration & dosage , Sodium Pertechnetate Tc 99m/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , Time Factors , Tomography, Emission-Computed, Single-Photon/adverse effects , Young Adult
2.
J Nucl Med ; 58(5): 791-798, 2017 May.
Article in English | MEDLINE | ID: mdl-27738005

ABSTRACT

A single-site prospective open-label clinical study with cyclotron-produced sodium 99mTc-pertechnetate (99mTc-NaTcO4) was performed in patients with indications for a thyroid scan to demonstrate the clinical safety and diagnostic efficacy of the drug and to confirm its equivalence with conventional 99mTc-NaTcO4 eluted from a generator. Methods:99mTc-NaTcO4 was produced from enriched 100Mo (99.815%) with a cyclotron (24 MeV; 2 h of irradiation) or supplied by a commercial manufacturer (bulk vial eluted from a generator). Eleven patients received 325 ± 29 (mean ± SD) MBq of the cyclotron-produced 99mTc-NaTcO4, whereas the age- and sex-matched controls received a comparable amount of the generator-derived tracer. Whole-body and thyroid planar images were obtained for each participant. In addition to the standard-energy window (140.5 keV ± 7.5%), data were acquired in lower-energy (117 keV ± 10%) and higher-energy (170 keV ± 10%) windows. Vital signs and hematologic and biochemical parameters were monitored before and after tracer administration. Results: Cyclotron-produced 99mTc-NaTcO4 showed organ and whole-body distributions identical to those of conventional 99mTc-NaTcO4 and was well tolerated. All images led to a clear final diagnosis. The fact that the number of counts in the higher-energy window was significantly higher for cyclotron-produced 99mTc-NaTcO4 did not influence image quality in the standard-energy window. Image definition in the standard-energy window with cyclotron-produced 99mTc was equivalent to that with generator-eluted 99mTc and had no particular features allowing discrimination between the 99mTc production methods. Conclusion: The systemic distribution, clinical safety, and imaging efficacy of cyclotron-produced 99mTc-NaTcO4 in humans provide supporting evidence for the use of this tracer as an equivalent for generator-eluted 99mTc-NaTcO4 in routine clinical practice.


Subject(s)
Cyclotrons/instrumentation , Radiation Injuries/etiology , Sodium Pertechnetate Tc 99m/adverse effects , Sodium Pertechnetate Tc 99m/pharmacokinetics , Thyroid Diseases/diagnostic imaging , Thyroid Diseases/metabolism , Adult , Aged , Aged, 80 and over , Equipment Design , Female , Humans , Isotope Labeling/instrumentation , Male , Metabolic Clearance Rate , Middle Aged , Organ Specificity , Radiation Injuries/diagnosis , Radiation Injuries/prevention & control , Radionuclide Generators , Radiopharmaceuticals/adverse effects , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/pharmacokinetics , Reproducibility of Results , Sensitivity and Specificity , Sodium Pertechnetate Tc 99m/chemical synthesis , Tissue Distribution
3.
PLoS One ; 9(3): e92729, 2014.
Article in English | MEDLINE | ID: mdl-24663284

ABSTRACT

Low-energy Auger and conversion electrons deposit their energy in a very small volume (a few nm3) around the site of emission. From a radiotoxicological point of view the effects of low-energy electrons on normal tissues are largely unknown, understudied, and generally assumed to be negligible. In this context, the discovery that the low-energy electron emitter, 99mTc, can induce stunning on primary thyrocytes in vitro, at low absorbed doses, is intriguing. Extrapolated in vivo, this observation suggests that a radioisotope as commonly used in nuclear medicine as 99mTc may significantly influence thyroid physiology. The aims of this study were to determine whether 99mTc pertechnetate (99mTcO4-) is capable of inducing thyroid stunning in vivo, to evaluate the absorbed dose of 99mTcO4- required to induce this stunning, and to analyze the biological events associated/concomitant with this effect. Our results show that 99mTcO4--mediated thyroid stunning can be observed in vivo in mouse thyroid. The threshold of the absorbed dose in the thyroid required to obtain a significant stunning effect is in the range of 20 Gy. This effect is associated with a reduced level of functional Na/I symporter (NIS) protein, with no significant cell death. It is reversible within a few days. At the cellular and molecular levels, a decrease in NIS mRNA, the generation of double-strand DNA breaks, and the activation of the p53 pathway are observed. Low-energy electrons emitted by 99mTc can, therefore, induce thyroid stunning in vivo in mice, if it is exposed to an absorbed dose of at least 20 Gy, a level unlikely to be encountered in clinical practice. Nevertheless this report presents an unexpected effect of low-energy electrons on a normal tissue in vivo, and provides a unique experimental setup to understand the fine molecular mechanisms involved in their biological effects.


Subject(s)
Sodium Pertechnetate Tc 99m/adverse effects , Thyroid Gland/radiation effects , Animals , Biological Transport , DNA Breaks, Double-Stranded/radiation effects , Electrons , Female , Gene Expression Regulation/radiation effects , Mice , RNA, Messenger/genetics , RNA, Messenger/metabolism , Radiometry , Sodium Pertechnetate Tc 99m/metabolism , Symporters/genetics , Symporters/metabolism , Thyroid Gland/cytology , Thyroid Gland/metabolism , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed
4.
J Nucl Med ; 52(9): 1418-22, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21795365

ABSTRACT

UNLABELLED: After the extravasation of a therapeutic dose of (131)I-metaiodobenzylguanidine that produced a radiation burn to a patient's forearm, we instituted a catheter placement verification protocol. METHODS: Before therapy infusion, proper placement is verified by administering 37 MBq of (99m)Tc-pertechnetate through the catheter, and monitoring activity at the administration site and on the contralateral extremity. A dosimetric model describing both high-rate and low-rate dose components was developed and predicted that the basal epidermal layer received a radiation dose consistent with the observed moist desquamation radiation skin toxicity. RESULTS: No extravasation incidents have occurred since the verification procedure was instituted. CONCLUSION: To protect against radiation injury from extravasation of therapeutic radionuclides, test administration of a small (99m)Tc dose with probe monitoring of comparable sites in both upper extremities appears to be an effective preventive measure.


Subject(s)
3-Iodobenzylguanidine/administration & dosage , 3-Iodobenzylguanidine/adverse effects , Extravasation of Diagnostic and Therapeutic Materials , Radiopharmaceuticals/administration & dosage , Radiopharmaceuticals/adverse effects , 3-Iodobenzylguanidine/therapeutic use , Algorithms , Beta Particles , Dermis/blood supply , Infusions, Intravenous , Models, Theoretical , Photons , Radiometry/methods , Radiopharmaceuticals/therapeutic use , Regional Blood Flow/physiology , Skin/blood supply , Skin/radiation effects , Sodium Pertechnetate Tc 99m/adverse effects
5.
Ann Pharm Fr ; 69(3): 182-91, 2011 May.
Article in French | MEDLINE | ID: mdl-21570543

ABSTRACT

INTRODUCTION: The exposure of workers to antineoplastic agents is potentially dangerous in the long term because of the teratogenic, carcinogenic and mutagenic hazardous of these products. These risks could be reduced by individual and collective shield measures. It's recommended to use transfer devices in a closed system for preparation of chemotherapy. METHOD: The aim of the survey is to analyse for five devices (four devices in a closed system transfer and a needle equipped with an air intake), the following criteria: transfer performance of a solution of a vial to another one, no leakage of the device and practicality in the use. A method implementing a radioactive solution of sodium pertechnetate [(99m)Tc] is used. RESULTS: Teva(®) and Cardinal(®) devices seem to be more efficient according to the ability to transfer one solution from a vial to another one with a low dead volume and low-level contamination in the around of the manipulation area. The Hospira(®) device appears an intermediate solution, while the Phaseal(®) device may be irrelevant for the transfer of a solution. DISCUSSION-CONCLUSION: Our study could attest that the methodology is simple to implement and cheap to compare devices on multiple selection criteria. This evaluation method is interesting because it allows a classification according to several criteria weighted according to the type of intended use. In addition to economic issues and protection of the worker, the use of such devices should be extended to other areas as the preparation of chemotherapy such as preparation of radiopharmaceuticals drugs.


Subject(s)
Occupational Exposure/prevention & control , Sodium Pertechnetate Tc 99m/administration & dosage , Sodium Pertechnetate Tc 99m/adverse effects , Drug Compounding , Drug Therapy/instrumentation , Humans , Needles , Sodium Pertechnetate Tc 99m/analysis , Solutions
6.
Acta Physiol Hung ; 93(2-3): 131-6, 2006 Jun.
Article in English | MEDLINE | ID: mdl-17063624

ABSTRACT

The majority of radiation injury in cells depends on oxidative stress. Irradiation and absorbed doses, duration of the irradiation and the susceptibility of the tissue against radiation are the factors that cause variations on living cells. The aim of this study was to investigate gamma radiation-induced oxidative damage in erythrocytes after thyroid scintigraphy with Tc-99m pertechnetate. Fifteen patients (8 women and 7 men) who performed thyroid scintigraphy with Tc-99m pertechnetate were included in this study. The median age was 52 +/- 8 years (range 33-65). The blood samples were taken from patients just before, 1 hour after and three hours after injection of radiopharmaceutical. Malondialdehyde (MDA) and antioxidant enzymes such as glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) levels were measured to evaluate the gamma radiation induced oxidative damage. No difference was detected in any final measurement activities of erythrocyte antioxidant enzyme such as SOD and GPX in the direct comparison between the before and after injection of the radiopharmaceutical groups, except erythrocyte CAT activities measured 1 hour after and 3 hours after injection of the radiopharmaceutical (p < 0.05). MDA levels were decreased 1 hour after and 3 hours after injection of the radiopharmaceutical.


Subject(s)
Erythrocytes/radiation effects , Oxidative Stress , Sodium Pertechnetate Tc 99m/adverse effects , Thyroid Gland/diagnostic imaging , Adult , Aged , Antioxidants/metabolism , Catalase/blood , Female , Glutathione Peroxidase/blood , Humans , Male , Malondialdehyde/blood , Middle Aged , Radionuclide Imaging , Superoxide Dismutase/blood
7.
Int J Radiat Biol ; 80(11-12): 875-80, 2004.
Article in English | MEDLINE | ID: mdl-15764396

ABSTRACT

OBJECTIVE: To study the biological effectiveness of Auger electrons emitted by (99m)Tc on cell survival, induction of apoptosis and micronucleus (MN) formation in the human squamous cell carcinoma cell line SCL-II and compare the effects observed to those observed after exposure to external 60Co gamma radiation. MATERIAL AND METHODS: Cells were either gamma(60Co)-irradiated (0.67 Gy/min) or exposed to (99m)Tc-pertechnetate (0.95-14.3 MBq/ml) for 24 h under cell culture conditions and assayed for cell survival (colony-forming assay), micronucleus formation (cytochalasin B assay) and the frequency of apoptotic cells (fluorescence microscopy). Monte Carlo based dosimetry has been applied to derive the absorbed dose corresponding to the accumulated decays of (99m)Tc under the given geometry. RESULTS: Absorbed doses up to 0.5 Gy could be achieved after 99mTc-exposure leading to no substantial cell killing in this dose range except at one dose point (0.1 Gy) resulting in an relative biological effectiveness (RBE)SF 0.9 of 0.64 when compared to the 60Co reference radiation. MN formation was described best by a linear dose response and was consistently lower after 99mTc exposure when compared to 60Co irradiated cells resulting in an RBE of 0.37. Apoptosis induction was significantly increased after 99mTc exposure at much lower doses (0.1 Gy) when compared to the reference radiation. The (99m)Tc uptake experiments revealed an activity concentration ratio cells vs. medium of 0.07 after 24 h of exposure. CONCLUSION: No overall increased biological effectiveness due to the emitted Auger electrons of (99m)Tc, applied as sodium-pertechnetate, could be observed in the investigated cell line when compared to acute external gamma radiation. The RBEs in the range of 0.37-0.64 might be well explained by dose rate effects. The significantly increased apoptotic response after (99m)Tc-exposure at very low doses has to be further investigated.


Subject(s)
Apoptosis/radiation effects , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/physiopathology , Cell Survival/radiation effects , Micronuclei, Chromosome-Defective/radiation effects , Sodium Pertechnetate Tc 99m/adverse effects , Cell Line, Tumor/pathology , Cell Line, Tumor/radiation effects , Cobalt Radioisotopes/adverse effects , Dose-Response Relationship, Radiation , Electrons/adverse effects , Humans , Micronucleus Tests , Radiation Dosage , Radiopharmaceuticals/adverse effects
8.
Eur J Nucl Med Mol Imaging ; 29(10): 1365-73, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12271420

ABSTRACT

Organ residence times were calculated for diagnostic intakes of (99m)Tc pertechnetate, 2,3-dimercaptosuccinic acid (DMSA), diethylene triamine penta-acetic acid (DTPA), hydroxymethylene diphosphonate (HDP), macroaggregated albumin (MAA) and mercapto-acetyltriglycine (MAG(3)) during the 1st and 3rd stages of pregnancy and used with the MIRDOSE3 pregnant female phantoms for generation of dose estimates. At stage 3 individual foetal organ doses were estimated via a surrogate phantom based on that for the new-born but with mean dose/cumulated activity ( S) values scaled for compatibility with foetal whole body S. Stage 1 or 3 whole foetus doses ranged from 5.2 to 0.77 microGy MBq(-1) respectively, analogous to current ICRP estimates for these agents using similar in vivo biodistribution model databases. Most stage 3 maternal and foetal organ doses were similar within a factor of 3, being higher in the foetus than the mother with pertechnetate, DTPA and MAG(3), and lower with DMSA, HDP and MAA. Doses were more uniformly distributed among foetal organs than in the mother. Placental transfer was greatest with pertechnetate, where dose to the stage 3 foetal thyroid was 60-140 microGy MBq(-1). With each agent there was more placental transfer in stage 3 than in stage 1, but doses to stage 1 whole foetus were always higher, with the contribution from the mother dominant. For DMSA, HDP and MAG(3) the maternal contribution to total foetal body dose exceeded 93% for both stages.


Subject(s)
Fetus/metabolism , Fetus/radiation effects , Maternal-Fetal Exchange , Organ Specificity , Organotechnetium Compounds/pharmacokinetics , Whole-Body Counting/methods , Animals , Female , Fetus/diagnostic imaging , Guinea Pigs , Humans , Models, Biological , Organotechnetium Compounds/adverse effects , Organotechnetium Compounds/classification , Pregnancy , Pregnancy Trimesters , Radiation Dosage , Radiometry/methods , Radiometry/standards , Radionuclide Imaging , Radiopharmaceuticals/adverse effects , Radiopharmaceuticals/pharmacokinetics , Sensitivity and Specificity , Sodium Pertechnetate Tc 99m/adverse effects , Sodium Pertechnetate Tc 99m/pharmacokinetics , Tissue Distribution , Whole-Body Counting/standards
9.
Br J Radiol ; 65(773): 403-8, 1992 May.
Article in English | MEDLINE | ID: mdl-1319255

ABSTRACT

Inhalation of the ventilatory radiopharmaceutical 99Tcm Technegas leads, in some patients, to symptoms that may be attributed to temporary lowering of oxygen saturation. In order to evaluate this, oxygen saturation was measured by pulse oximetry in a series of patients undergoing Technegas ventilation scintigraphy. A decrease in oxygen saturation was recorded in 87% of the patient group. The mean change, as a percentage of the initial value, was 8.3% (range 1-24%). Hypoxia arising in association with Technegas administration may be reduced by pre-oxygenation. In patients who were pre-oxygenated, oxygen saturation did not fall below 85% (PaO2: 50 mmHg) but in 39% of those not pre-oxygenated the value fell below this level. Oxygen saturation was also monitored in a series of patients undergoing perfusion scintigraphy. In 17% of patients a decrease was recorded (range 2-11%). In view of the large number of perfusion scans performed annually in this department and elsewhere without untoward effect, such temporary decreases in oxygen saturation presumably present no hazard to the patient.


Subject(s)
Hypoxia/etiology , Lung/diagnostic imaging , Sodium Pertechnetate Tc 99m/adverse effects , Technetium Tc 99m Aggregated Albumin/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Albumins/adverse effects , Female , Graphite/adverse effects , Humans , Male , Middle Aged , Oxygen/administration & dosage , Oxygen/blood , Radionuclide Imaging
10.
Radiology ; 182(3): 727-30, 1992 Mar.
Article in English | MEDLINE | ID: mdl-1311117

ABSTRACT

The frequency, nature, and duration of postprocedural symptoms in 100 children who underwent voiding cystourethrography (VCUG) after administration of 17.2% wt/vol iothalamate meglumine, 100 children who underwent radionuclide cystography (RNC) after administration of saline and technetium-99m pertechnetate, and 28 children catheterized before diuretic renal scintigraphy (DRS) were prospectively assessed with telephone follow-up. All children were aged 2 years or older; 61 were boys, 167 were girls. Postprocedural symptoms occurred in 80 children (35.1%). The frequency of postprocedural symptoms was nearly identical in the VCUG group and the two other groups. Boys (n = 33 [54%]) had symptoms significantly more often than girls (n = 47 [28%]) (P less than or equal to .0005). Dysuria was the most common symptom (n = 75 [32.9%]) and was frequently accompanied in younger children by anxiety over going to the bathroom. Symptoms disappeared within 24 hours in 32 of 80 children (40%) and lasted 4-10 days in eight children. It is concluded that most postprocedural symptoms in children who undergo VCUG, RNC, or DRS are secondary to catheterization rather than to the use of iodinated contrast material.


Subject(s)
Contrast Media/adverse effects , Radioisotope Renography/adverse effects , Urinary Bladder/diagnostic imaging , Urinary Catheterization/adverse effects , Urination Disorders/etiology , Urography/adverse effects , Child , Female , Humans , Iothalamate Meglumine/adverse effects , Male , Prospective Studies , Sodium Pertechnetate Tc 99m/adverse effects , Urination Disorders/epidemiology
11.
Nucl Med Commun ; 8(10): 839-45, 1987 Oct.
Article in English | MEDLINE | ID: mdl-2829070

ABSTRACT

Measurements were made of the concentration of radioactivity in the breast milk of two patients: one following 100 MBq (2.7 mCi) 99Tcm-pertechnetate administration, and the other following administration of 550 MBq (15 mCi) 99Tcm-glucoheptonate. The fractional activity concentrations in the former case were about two orders of magnitude greater than in the latter and the effective half lives of secretion were 3 and 4 h, respectively. An infant breast fed without interruption would have ingested 5.2 and 0.055% of the 99Tcm administered with pertechnetate and with glucoheptonate, respectively. The former fractional ingestion was compatible with the larger value expected following pertechnetate injection without perchlorate pretreatment, and would have produced an effective dose equivalent to the infant of 1.5 mSV. An interruption to feeding of 12 h would reduce this dose to 0.2 mSV. It was concluded that breast feeding need not be interrupted after injection of 99Tcm-glucoheptonate other than for a short period of reassurance.


Subject(s)
Breast Feeding , Milk, Human/radiation effects , Organotechnetium Compounds , Sodium Pertechnetate Tc 99m/pharmacokinetics , Sugar Acids/pharmacokinetics , Technetium/pharmacokinetics , Adult , Female , Humans , Infant , Injections , Milk, Human/metabolism , Radioactivity , Sodium Pertechnetate Tc 99m/adverse effects , Sugar Acids/adverse effects , Technetium/adverse effects
12.
Scand J Clin Lab Invest ; 45(8): 717-24, 1985 Dec.
Article in English | MEDLINE | ID: mdl-3001924

ABSTRACT

The aim of this study was to assess the cytotoxicity of a new leucocyte-labelling method, which may be used clinically to localize inflammatory and immune reactions. Human blood leucocytes, their mononuclear sub-population, and mouse mononuclear bone marrow cells were labelled with 99mTc for 30-45 min, washed once, and then evaluated in various functional assays. The new procedure includes [99mTc]-labelling with a bisalt method, in the presence of dihydroxybenzoic acid as an intermediate antioxidant-complexing stabilizer, and a carboxylic acid salt of stannous ions as a reducing agent. To challenge the method, cells were labelled about two orders of magnitude more heavily in these initial methodological studies than in on-going clinical trials. Labelled leucocytes ingested latex beads as readily as the controls, but migrated chemotactically and randomly somewhat slower than the control cells. The lymphocytes were triggered by PHA and Con A in a normal way. However, lymphocytes and haemopoietic progenitor cells exposed to radiation for several days, were killed by the isotope doses used, of which about 2% (i.e. 20 MBq) were bound per million cells. All deleterious effects were apparently due to irradiation, and the labelling procedure itself did not damage the cells.


Subject(s)
Isotope Labeling/methods , Leukocytes/immunology , Sodium Pertechnetate Tc 99m , Cell Migration Inhibition , Cells, Cultured , Humans , Leukocytes/radiation effects , Lymphocyte Activation/radiation effects , Phagocytosis/radiation effects , Sodium Pertechnetate Tc 99m/adverse effects
13.
Radiology ; 156(1): 183-5, 1985 Jul.
Article in English | MEDLINE | ID: mdl-2988011

ABSTRACT

According to a 1981 survey of thyroid imaging methods in the United States, radionuclide thyroid scans and uptake studies increased 250%-300% between 1966 and 1981, while the U.S. population increased only 17%. Collective absorbed dose decreased from 18 X 10(6) rad (18 X 10(4) Gy) in 1966 to 13.9 X 10(6) rad (13.9 X 10(4) Gy) in 1981. The decrease was due to the use of iodine 123 and technetium 99m pertechnetate rather than iodine 131 (I-131 was used for 100% of scans and uptake studies in 1966 and 10% and 54%, respectively, in 1981) and also to fewer free-standing thyroid uptake studies (150,000 in 1966 and 33,000 in 1981). Even with reduced usage, I-131 still accounted for 93% of the collective absorbed dose in 1981. If I-131 were eliminated from diagnostic procedures, the annual absorbed dose would decrease to 1.4 X 10(6) rad (1.4 X 10(4) Gy). The number of radiation-induced cancer cases would also be reduced.


Subject(s)
Neoplasms, Radiation-Induced/prevention & control , Thyroid Gland/diagnostic imaging , Thyroid Neoplasms/prevention & control , Humans , Iodine Radioisotopes/adverse effects , Neoplasms, Radiation-Induced/etiology , Radiation Dosage , Radionuclide Imaging , Risk , Sodium Pertechnetate Tc 99m/adverse effects , Thyroid Gland/radiation effects , Thyroid Neoplasms/etiology , United States
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