Treatment for Internal Contamination with Radionuclides Doran Christensen, DO Associate Director, REAC/TSSlide 2
Objectives Understand Principles of Incorporation Know Action Levels for Treatment Know Five Most Common Types of Internal ContaminationSlide 3
4 Golden Rules of Toxicology (Adapted from Kent Olson, MD FACEP) Treat the Patient before the Poison Prevent or Reduce Exposure Enhance the Elimination of the Agent Consider Specific AdjunctsSlide 4
Annual Limit of Intake as far as possible for the measure of radioactive material taken into the body of a grown-up laborer by inward breath or ingestion in a year. ALI is the littler estimation of admission of a given radionuclide in a year by the reference man that would bring about a submitted compelling dosage likeness 5 rems(0.05 sievert) or a conferred measurements likeness 50 rems (0.5 sievert) to any individual organ or tissue. (see 10 CFR 20.1003 .)Slide 5
Radiation Accidents can Pose Toxicology Problems The Dose makes the Poison Acute (Threshold Effects) Long-Term Toxicity ALI/MPBB < 1 ALI -No Treatment Necessary 1 - 10 ALI -Consider Short-Term Tx > 10 ALI -Treatment 1 Radiation Protection Dosimetry, Vol 41, No 1, 1992, p. 25Slide 6
Sample ALIs Radioisotope ALI-Ingestion ALI-Inhalation (mCi) (mCi) 3 H 80 80 14 C 2 2 32 P 0.6 0.6 33 P 6 8 35 S 10 20 125 I 0.04 0.06 Source – Princeton University, Environmental Health & SafetySlide 7
Psychological Aspects of Internal Contamination Radiation Exposure Sometimes Continues Long after Accident Estimates of Dose and Effects are distressingly Variable even among ExpertsSlide 8
Radionuclides versus Different Hazardous Materials Easily Detectable Use Health Physicist Instead of Industrial Hygienist Does not Require Special Clothing for Health Care Providers Not an Immediate Life-Threatening Hazard Can Wait until Patient is Stable before DecontaminationSlide 9
Use Your Medical or Health Physicist Document Presence of Radionuclides, Activity, Accident Details Collect Samples Documenting Contamination Assist in Decontamination Procedures Calculate/Document Dose Calculations Dispose of Radioactive WasteSlide 10
Bioassay is of Limited Value Slow (Days) Must Have Total Collection of Both Urine and Feces Can Overestimate Uptake by Factor of 3 - 5 Specimen May Get ContaminatedSlide 11
Whole Body Counting Difficult with Actinides Residual Skin Contamination Calibration of Phantoms Deficient Lung Distribution Varies with Time Variable Thickness of Sternum/Chest WallSlide 12
Toxicologic Problem: (Gather Data) Details Radionuclides Involved Laboratory License Maximum Credible Exposure Geometry, Distances, Times Potential for Exposure Poison Control AnalogySlide 13
Hospital Resources Radiologist or Nuclear Medicine Physician Medical or Health Physicist Radiation Safety Officer ( RSO ) Nuclear Medicine Decontamination Area Nuclear Medicine Gamma CameraSlide 14
Hospital NM Gamma Camera For Selected Internal Contamination Radionuclide WBC (MDA in air) Gamma Camera (MDA in air) G-M Survey Counter Scatter Media (MDA in air) 125 I 030-2.62 3.68-29.90 90 201 Tl 0.20 0.51-0.69 2.40-3.48 188 99m Tc 0.09 0.37-0.39 1.15-1.53 144 111 In 0.12 0.40-0.56 1.36-1.64 165 133 Ba 0.11 0.71-0.89 1.88-2.50 20 131 I 0.12 0.56-1.09 1.51-2.71 59 85 Sr 0.11 0.68-0.99 1.85-3.22 90 137 Cs 0.13 1.04-2.26 2.47-4.03 59 54 Mn 0.10 1.06-1.84 2.70-4.24 38 60 Co 0.10 1.27i-1.48 2.11-3.15 14Slide 15
External Resources State Radiological Health Department Radiation Emergency Assistance Center/Training Site (REAC/TS) - 865/576-1005 CHEMTREC (for HazMat segments just) 800/424-9300Slide 16
Other External Resources Agency for Toxic Substances Disease Registry (ATSDR) 24 Hour Line 404/639-0615 (No Answer) Dept Of Energy (DOE) Emergency Operations Center 24 Hour Line 202/586-8100 Nuclear Regulatory Commission (NRC) 24 Hour Line 301/816-5100 301/951-0550Slide 17
Internal Contamination Ramifications Isolation During Therapy? Follow-up for Possibly Long Periods Counseling for Carcinogenic Implications of ExposureSlide 18
Internal Contamination - Involves 4 Stages Deposition Along Route of Entry Translocation Incorporation (Deposition in the Target Organ) ClearanceSlide 19
Preventing Incorporation Interception Before Radionuclide Reaches Target Organs Decrease Body Uptake Vomit/Lavage Charcoal/Catharsis Other MethodsSlide 20
Considerations in Treatment for Internal Contamination Chemical Toxicity of Substance Solubility (D,W,Y) Particle Size Quantity Half-existence of Radionuclide: Physical Biological EffectiveSlide 21
Respiratory Tract Clearance Time 1 Segment Time (hours) Anterior nare 1.0 Nasopharynx 0.1 (10 mm/min) Trachea 0.1 Bronchi 1.0 Bronchioles 4.0 Terminal Bronchioles 10.0 Alveoli 100+ days 1 ICRP #30 Model (1979)Slide 22
Particle Size and Deposition FractionSlide 23
Nasopharynx Clearance Time 1 Anatomy Clearance Time (min) Anterior nare 60 Nasopharynx 10 (10 mm/min) 1 ICRP #30 Model (1979)Slide 24
Gastrointestinal Tract Residence Times 1 Portion Residence Time (hours) Stomach 6/24 Small Intestine 14/24 Upper Colon 18/24 Lower Colon 24/24 1 ICRP #30 Model (1979) (Assumes Stable Substances)Slide 25
Schematic Model of Radionuclide Uptake (After Voelz) Ingestion Inhalation Surface Intake: Lung Clearance Skin 1. In place 2. Wounds Lung GI Tract Lymph Nodes Uptake: Blood (Recycle) Kidney Deposition Sites 1. Entire Body 2. Bone 3. Liver 4. Thyroid Excretion: Feces UrineSlide 26
Treatment of Internal Emitters TIME: Within 3 hrs, if Possible BENEFIT: 2 to 10 Reduction of Organ Dose RISKS: Minimal, aside from Lung Lavage/ Some Drugs DECISION: Go to Potential Exposure History, Not DoseSlide 27
Physiologic Principles Used in Radionuclide Decorporation GI Tract Removal/Enhanced Elimination Dilution of Isotope Displacement Blocking Alkalinization ChelationSlide 28
Reduction of Absorption from Gastrointestinal Tract Antacid Precipitation into Soluble Salt CatharsisSlide 29
Iodine/Technetium - Block 131 I - Eff Half Life = 7.6 days 99m Tc - Eff Half Life = 1 day* Treat inside 4 Hours ( Best 1 Hour Before Exposure! ) KI or NaI 300 mg tablet SSKI (1 g/ml) - 5 - 6 drops in water Povidone Iodine Theoretically Useful NCRP Report No 65, p 83-86, 104Slide 30
Tritium - Dilute Beta Emitter 2% Binds to Cellular Components Essentially Occupies TBW Space Force Fluids 3 - 4 L/day Reduces Half-Time by 1/3 - 1/2 NCRP Report No 65, p 105-106Slide 31
Beer Therapy for TritiumSlide 32
Chelation Agents DTPA - Transuranics (not Uranium) EDTA - Lead (and others) BAL - Lead, Polonium, Gold, Indium DFOA - Iron, Manganese PCA - Copper, Lead, Mercury , Zinc, Cobalt, Gold DMPS - Mercury (not in US) DMSA - Lead (and Others)Slide 33
Comparison of EDTA and DTPA HOOC-H 2 C CH 2 - COOH N-CH 2 - CH 2 - N CH 2 - COOH HOOC-H 2 C EDTA - Ethylenediaminetetraacetic Acid CH 2 - COOH HOOC-H 2 C N-CH 2 - CH 2 - N-CH 2 - CH 2 - N CH 2 HOOC-H 2 C CH 2 - COOH DTPA - Diethylenetriaminepentaacetic AcidSlide 34
DTPA Administered for Soluble 239 Pu Within One Hour Retention Organ Control DTPA Treated Liver 14% 0.47% Skeleton 57.0% 5.9%Slide 35
Insoluble Prussian Blue Effective for Cs-137 Binds Ions in the Gut Biological Half-Life Reduced to 1/3 Not Systemically Absorbed Side Effects - Constipation, GI Upset at Higher Doses (20 g/day)Slide 36
Lung Lavage Does Not Need to be Done Emergently 1 ( 3-5 days after Exposure ) Lavage Technique for Pulmonary Alveolar Proteinosis For bigger testimonies 50 2 - 100 1 ALIs Common Bronchoscopic Lavage (has not been assessed for adequacy) 1 Radiation Protection Dosimetry, Vol 41, No 1, 1992, pp. 32-33. 2 Safety Series No. 47, Vienna: IAEA, 1978, p 23.Slide 37
Uranium Compounds and Solubility Classes 1 Solubility Compound Class UF 6 (Uranium Hexafluoride) D UO 2 (NO 3 ) 2 (Uranyl Nitrate) D UO 3 (Uranium Trioxide) D UO 2 Cl 2 (Uranyl Chloride) D UO 4 (Uranium Peroxide) W UO 2 (Uranium Dioxide) W,Y UC 2 (Uranium Dicarbide) Y UO 2 (High-Fired Uranium Dioxide) Y 1 Adapted From Biokinetics and Analysis of Uranium in Man , Hanford Environmental Health Foundation for the US Dept of Energy, 1984Slide 38
Uranium in Biological Fluids pH 6.5 - 8 Principal/Most Easily Transported Form of Serum U is Biscarbonato Complex, UO 2 (CO 3 ) 2+ Uranyl Citrate Complex likewise shaped Weak Complex of UO 2 2+ and Iron-Transport Protein, Transferrin additionally Forms in Plasma Adapted From Biokinetics and Analysis of Uranium in Man , Hanford Environmental Health Foundation for the US Dept of Energy, 1984Slide 39
Uranium Deposition in Kidney Some of Bound UO 2 2+ is Retained in Kidney Renal Retention Enhanced by: Large Amounts of U Acidic Urine U Kidney Release Half-time is 15 d Enhanced by Alkaline Urine Adapted From Biokinetics and Analysis of Uranium in Man , Hanford Environmental Health Foundation for the US Dept of Energy, 1984Slide 40
Uranium - Alkalinize Urine 235 U - Gamma Eff Half Time Depends on Solubility At Normal Enrichment Levels, Primary Renal Toxicity Maintain Urine pH 7.5 to 8 Use Bicarbonate tablets (Do not utilize Alka Seltzer from old writings!) Use Supplemental KCl tablets
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