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EVALUATION OF CUPRIMINE® AND SYPRINE® FOR DECORPORATION OF 60Co AND 210Po

Levitskaia, Tatiana G.*; Creim, Jeffrey A.*; Curry, Terry L.*; Luders, Teresa*; Morris, James E.*; Woodstock, Angela D.*; Levinson, Barry; Thrall, Karla D.*

doi: 10.1097/HP.0b013e3181bcdf4f
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The acknowledged risk of deliberate release of radionuclides into local environments by terrorist activities has prompted a drive to improve novel materials and methods for removing internally deposited radionuclides. These decorporation treatments will also benefit workers in the nuclear industry, should an exposure occur. Cuprimine® and Syprine® are oral therapeutics based on the active ingredients D-penicillamine and N,N′-bis-(2-aminoethyl)-1,2-ethanediamine dihydrochloride, respectively. These therapeutic drugs have been used for several decades to treat Wilson's disease, a genetic defect leading to copper overload, by chelation and accelerated excretion of internally deposited copper. Studies were undertaken to evaluate these FDA-approved drugs for the in vivo decorporation of radioactive cobalt (60Co) and polonium (210Po) using male Wistar-Han rats. In these studies, 60Co or 210Po was administered to animals by IV injection, followed by oral gavage doses of either Cuprimine® or Syprine®. Control animals received the radionuclide alone. For 60Co studies, animals received a single dose of Cuprimine® or Syprine®, while for 210Po studies animals were repeatedly dosed at 24-h intervals for a total of 5 doses. Results show that Syprine® significantly increased urinary elimination and skeletal concentrations of 60Co compared to controls. While Cuprimine® had little effect on total excretion of 60Co, the skeletal, kidney, liver, muscle, and stomach tissues had significantly lower radioactivity compared to control animals. The low overall excretion of 210Po made it difficult to reliably measure urinary or fecal radioactivity and draw a definitive conclusion on the effect of Cuprimine® or Syprine® treatment on excretion. However, Cuprimine® treatment was effective at reducing spleen levels of 210Po compared to controls. Similarly, Syprine® treatment produced statistically significant reductions of 210Po in the spleen and skeletal tissues compared to control animals. Based on these promising findings, further studies to evaluate the dose-response pharmacokinetic profiles for decorporation are warranted.

* Battelle, Pacific Northwest Division, 902 Battelle Blvd, Mail Stop P7-25, Richland, WA 99352; † Aton Pharma, Inc., 3150 Brunswick Pike, Suite 230, Lawrenceville, NJ 08648.

For correspondence contact: T. Levitskaia, Battelle, Pacific Northwest Division, 902 Battelle Blvd, Mail Stop P7-25, Richland, WA 99352, or email at tatiana.levitskaia@pnl.gov.

(Manuscript accepted 18 August 2009)

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