Evaluation of Cuprimine and Syprine for decorporation of (60)Co and (210)Po.
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 (Co) and polonium (Po) using male Wistar-Han rats. In these studies, Co or Po was administered to animals by IV injection, followed by oral gavage doses of either Cuprimine or Syprine. Control animals received the radionuclide alone. For Co studies, animals received a single dose of Cuprimine or Syprine, while for Po 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 Co compared to controls. While Cuprimine had little effect on total excretion of Co, the skeletal, kidney, liver, muscle, and stomach tissues had significantly lower radioactivity compared to control animals. The low overall excretion of Po 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 Po compared to controls. Similarly, Syprine treatment produced statistically significant reductions of Po 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.
Levitskaia
Tatiana G
TG
Battelle, Pacific Northwest Division, Richland, WA 99352, USA. tatiana.levitskaia@pnl.gov
Creim
Jeffrey A
JA
Curry
Terry L
TL
Luders
Teresa
T
Morris
James E
JE
Woodstock
Angela D
AD
Levinson
Barry
B
Thrall
Karla D
KD
D000818:Animals; D002614:Chelating Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D003037:Cobalt Radioisotopes / Q000737:chemistry / Q000302:isolation & purification* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D010396:Penicillamine / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D011059:Polonium / Q000737:chemistry* / Q000302:isolation & purification* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014266:Trientine / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*
D002614:Chelating Agents; D003037:Cobalt Radioisotopes; D011059:Polonium; D010396:Penicillamine; D014266:Trientine