Ca-DTPA/Zn-DTPA
(Diethylentriamene pentaacetate)



Indications and Usage


  • According to FDA labeling, the chelating agents Ca-DTPA (FDA drug label, PDF - 121 KB) and Zn-DTPA (FDA drug label, PDF - 106 KB), salts of diethylentriamene pentaacetate (DTPA), are approved for the elimination of known or suspected internal contamination with the transuranic (Z > 92) metals plutonium, americium, and curium.
    • DTPA should not be used to chelate internal contamination with uranium or neptunium.
    • DTPA compounds are most effective if the metals to chelate are in soluble form.
    • Information about clinical decorporation with DTPA can be found on the FDA Web pages.
  • Use and Timing of DTPA
    • See details quoted below from FDA information about DTPA
      • “Ca-DTPA and Zn-DTPA should not be administered simultaneously.
      • FDA recommends that, if both products are available, Ca-DTPA be given as the first dose.
        • If additional treatment is needed, treatment should be switched to Zn-DTPA. This treatment sequence is recommended because Ca-DTPA is more effective than Zn-DTPA during the first 24 hours after internal contamination.
        • After the initial 24 hours, Zn-DTPA and Ca-DTPA are similarly effective, but Ca-DTPA causes more loss of essential metals, such as zinc, from the body. Therefore, Zn-DTPA is preferred for maintenance therapy.
        • If Ca-DTPA is not available or treatment cannot be started within the first 24 hours after contamination, treatment should begin with Zn-DTPA.
        • If Zn-DTPA is not available, Ca-DTPA can be given for continued treatment, along with vitamin or mineral supplements that contain zinc.
      • Ca-DTPA and Zn-DTPA can be administered by nebulizer or directly into the blood stream (i.e. intravenously).
        • If the route of internal contamination is through inhalation alone, then nebulized chelation therapy will suffice.
        • If the routes of contamination are multiple (e.g., inhalation and through wounds), then intravenous chelation therapy is preferred.
      • The duration of treatment is dictated by the level of internal contamination and the individual’s response to therapy.
        • Levels of internal contamination should be ascertained weekly during chelation therapy to determine when to terminate treatment.
      • Zn-DTPA is the preferred treatment for the pregnant woman with internal contamination.
      • In most cases of contamination with transuranium elements, it is unlikely that immediate illness would occur.
      • In order to reduce the risks of future biological effects, Ca-DTPA or Zn-DTPA should be taken as soon as possible after internal contamination, following or concurrent with distancing the individual from the radioactive source and appropriate external decontamination.
      • However, even when treatment cannot be started right away, individuals should be given Ca-DTPA or Zn-DTPA as soon as the products are available.
      • Treatment with Ca-DTPA or Zn-DTPA is still effective even after time has elapsed since contamination, but effectiveness decreases once these elements are trapped in the bones.
  • IV Dosing
    • Healthy, non-pregnant adults with normal bone marrow and renal function:
      • 1 g in 5 cc 5% dextrose in water (D5W) or 0.9% sodium chloride (normal saline, NS) slow IV push over 3-4 minutes OR
      • 1 g in 100-250 cc D5W or NS as an infusion over 30 minutes
    • Pregnant women:
      • Zn-DTPA should be used exclusively, if available.
      • Otherwise, use Ca-DTPA as a single-dose therapy and a multivitamin supplement that contains zinc. The same dose and dose schedule is used for Zn-DTPA as for Ca-DTPA.
      • See drug labels for discussion of issues related to use in pregnancy.
    • Children (<12 years old):
      • 14 mg DTPA/kg body weight/day in 5 cc D5W or NS slow IV push over 3-4 minutes (not to exceed 1 g/day).
      • Consult experts if treatment is needed in children < 2 years.
      • Safety and efficacy of nebulized route of administration has not been established in the pediatric population
    • DTPA dose should not be fractionated. It should only be given as a single dose, once per day.
    • The same dose and dose schedule are used for Zn-DTPA as for Ca-DTPA. Zn-DTPA may be administered for extended periods (weeks to months) in most cases without toxic effects.
    • The duration of DTPA therapy depends on
      • The amount of internal radioactive contamination
      • Each individual's response to therapy, i.e., rate of excretion of the metal
      • Excretion must be measured clinically to titrate the effectiveness of the chelation therapy.
      • Potential toxicity must be assessed during treatment. (See drug labels for Ca-DTPA and Zn-DTPA.
  • Nebulizer dosing
    • 1 g in 1:1 dilution with sterile water or NS, inhaled over 15-20 minutes
    • FDA recommends nebulized Zn-DTPA for adults whose internal contamination is only by inhalation. The inhaled Zn-DTPA may cause cough or wheezing in asthmatics.
      • The safety and efficacy of the nebulized route of administration has not been established in the pediatric population for Zn-DTPA.
  • Wound irrigation fluid dosing
    • 1 g Ca- or Zn-DTPA and 10 cc 2% lidocaine in 100 cc 5% D5W or NS
    • Irrigation can be accompanied by IV or inhaled DTPA.
    • The amount of DTPA absorbed by wound tissues cannot be measured.
    • Avoid overdosing with DTPA and/or 2% lidocaine.
  • Precautions
    • Since radioactive materials chelated to DTPA are excreted in urine, DTPA must be used carefully in people with diminished renal function.
    • The safety and effectiveness of the intramuscular route of Ca-DTPA or Zn-DTPA administration have not been established.
    • Toxicity is due to chelation of essential metals, such as Zn and Mn.
      • Toxicity includes nausea, vomiting, chills, diarrhea, fever, pruritus, and muscle cramps.
    • Ca-DTPA should be used with caution in patients with hemochromatosis (a genetic disease that causes the body to absorb too much iron from the diet).
  • Potential side effects of DTPA from FDA information quoted below.
    • “The main side effect of Ca-DTPA is loss of certain essential nutritional metals, such as zinc, from the body.
    • Zinc can be replaced by taking oral zinc supplements.
    • Although Zn-DTPA may also decrease the levels of certain nutritional metals, the effect (which can be countered by taking mineral supplements) is less than with Ca-DTPA.
    • Chelation therapy administered by nebulized inhalation may cause breathing difficulties in some individuals.
    • In addition, Ca-DTPA should be used with caution in patients suffering from a severe form of a disease called hemochromatosis.”
    • See drug label for information about pregnancy and breast feeding.

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References

  1. Management of Persons Contaminated with Radionuclides: Handbook (NCRP Report No. 161, Vol. I), National Council on Radiation Protection and Measurements, Bethesda, MD, 2008, Decorporation Therapy by Drug (pp. 191-198). [Note: NCRP 161 supersedes NCRP 65.]
  2. Management of Persons Contaminated with Radionuclides: Scientific and Technical Bases (NCRP Report No. 161, Vol. II), Bethesda, MD, 2010.
  3. Uncertainties in Internal Radiation Dose Assessment (NCRP Report No. 164), Bethesda, MD, 2009.