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Pentetate zinc trisodium and pentetate calcium trisodium (zinc or calcium diethylenetriaminepentaacetate; Zn-DTPA and Ca-DTPA, respectively) are chelators for certain heavy metals and radionuclides. They are approved for the treatment of internal contamination with plutonium, americium, and curium that may occur following unintentional exposure to these metals or following exposure resulting from a radiation dispersal device or “dirty bomb.”


First synthesized in 1954, these chelators were used investigationally to enhance elimination of transuranic elements (Chap. 12).3 DTPA has been used for the extraction of metals from soil and as a treatment for iron overload and lead toxicity.2,8,21 DTPA and its derivatives have also been used to help with imaging and diagnostics and more recently in chemotherapeutics. Over the last decades, hundreds of human exposures to radionuclides as well as numerous animal studies helped to define the best practices for the use of these chelators, culminating in their approval by the US Food and Drug Administration (FDA) in 2004.



Pentetic acid is a synthetic polyaminopolycarboxylic acid with a molecular weight of 393 Da; the calcium trisodium salt weighs 497 Da, and the zinc trisodium salt weighs 522 Da. It is slightly water soluble and bonds stoichiometrically with a central metal ion through the formal donation of one or more of its electrons.

Related Xenobiotics

Several xenobiotics are used in clinical practice to chelate metals. Among these are deferoxamine, dimercaptol (British anti-Lewisite), dimercapto-propane sulfonate, edetate calcium disodium (ethylenediaminetetraacetic acid), penicillamine, Prussian blue, succimer (dimercaptosuccinic acid), and trientine hydrochloride. However, none of these are effective chelators for transuranic (elements with atomic numbers > 92) metals.

DTPA is used to convey gadolinium contrast in magnetic resonance imaging and technetium in nuclear medicine imaging. Other xenobiotics have modified the DTPA molecule in conjunction with a monoclonal antibody directed toward specific antigens found on neoplasms, allowing an attached isotope, such as 111In, to deliver site directed radiation treatment. These related xenobiotics include tiuxetan, pendetide, and pentetreotide.17

Mechanism of Action

The conjugate base of pentetic acid has a high affinity for metal cations. Pentetic acid wraps itself around the metal forming up to eight bonds, exchanging its calcium or zinc ions for a metal with greater binding capacity (Fig. A44–1). Remaining water soluble, the chelated complex is then excreted by glomerular filtration into the urine. DTPA has specific stability constants for the various elements that it chelates, which presumably explains the different binding efficacies of the calcium and zinc salts.

Fig. A44–1

Trisodium zinc diethylenetriaminepentaacetate, where a transuranic element (Am, Pu, Cm) is substituted for Zn forming a stable chelate.

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