Pentetate zinc trisodium and pentetate calcium trisodium (zinc or calcium diethylenetriaminepentaacetate), Zn-DTPA and Ca-DTPA, are chelators approved for the treatment of internal contamination with plutonium (Pu), americium (Am), and curium (Cm). Both xenobiotics were first used investigationally in 1955 to enhance elimination of these transuranic elements.3 DTPA has also been used for the extraction of metals from soil,20 as a treatment for iron overload and lead toxicity,2,9 and as a chelator for Food and Drug Administration (FDA)-approved nuclear medical studies to prevent incorporation of injected radioisotopes.
DTPA is a synthetic polyamino polycarboxylic acid with a molecular weight of 522 daltons. It is water soluble and bonds stoichiometrically with a central metal ion through the formal donation of one or more of its electrons. In addition to the use of DTPA to chelate the transuranic elements Am, Pu, and Cm, there are also reports of its use in chelating patients contaminated with californium (Cf),17 and berkelium (Bk). The transuranic elements displace the calcium or zinc ion forming a stable DTPA-chelate complex (Fig. A43–1), which is then excreted in urine. DTPA has specific stability coefficients for the various elements that it chelates, which presumably explains the different binding efficacies of the calcium and zinc salts.
Trisodium zinc diethylenetriaminepentaacetate, where a transuranic element (Am, Pu, Cm) is substituted for Zn forming a stable chelate.
DTPA is not recommended or approved for treating patients contaminated with uranium (U) or neptunium (Np) for several reasons. DTPA mobilizes uranium from tissue stores but does not increase urinary elimination.6,15 Chelating incorporated Np is somewhat dependent on its valence Np+4 versus Np+5 but because it forms very stable complexes with transferrin it is very difficult to decorporate, and Np currently remains the subject of in vitro experiments combining DTPA with other chelators.7,14 While a systematic evaluation of all available data on DTPA efficacy for decorporation of transuranics has not been reported, it is nevertheless clear from many case reports that DTPA is very effective.
DTPA is rapidly absorbed via intramuscular, intraperitoneal, and intravenous routes. Animal studies show that DTPA is poorly (less than 5%) absorbed by the gastrointestinal tract. Absorption from the lungs is about 20% to 30%. Its volume of distribution is small (0.14 L/kg in humans) and is distributed throughout the extracellular space. It does not appear to penetrate well into erythrocytes or other cells. There is no binding of the chelate in the renal parenchyma, which is important to note since animal data showed severe lesions in the kidneys when exposed to 100-fold overdoses.5 The serum half-life is 20 to 60 minutes, although a small fraction is bound to plasma proteins with a half-life of more than 20 hours. DTPA undergoes minimal, if any, metabolism. Only a minimal release ...