title: Evaluation of Cuprimine® and Syprine® for decorporation of radioisotopes of cesium, cobalt, iridium and strontium.
abstract: Cuprimine® and Syprine® are therapeutics approved by the USFDA to treat copper overload in Wilson Disease (a genetic defect in copper transport) by chelation and accelerated excretion of internally-deposited copper. These oral therapeutics are based on the respective active ingredients D-penicillamine (DPA) and N,N'-bis (2-aminoethyl) -1,2-ethanediamine dihydrochloride (Trien). Cuprimine is considered the primary treatment, although physicians are increasingly turning to Syprine as a first-line therapy. Both drugs exhibit oral systemic activity and low toxicity; their biological effects and safety are established. Previous in vivo studies using a rodent animal model established the decorporation potential of Cuprimine and Syprine for (60)Co and (210)Po. Currently these studies are being expanded to evaluate the in vivo decorporation efficacy of these drugs for several additional radionuclides. In this report, results of this investigation are discussed using the radionuclides (137)Cs, (60)Co, (192)Ir and (85)Sr. Short-term 48-h pilot studies were undertaken to evaluate DPA and Trien for their in vivo decorporation potential using male Wistar-Han rats. In these studies, a radionuclide solution was administered to the animals by intravenous (IV) injection, followed by a single IV dose of either DPA or Trien. Control animals received the radionuclide alone. Results show effective decorporation of (60)Co by DPA within the time frame evaluated. DPA and Trien were also modestly effective in decorporation of (137)Cs and (85)Sr, respectively. The study did not find DPA or Trien effective for decorporation of (192)Ir. Based on these encouraging findings, further studies to evaluate the dose-response profiles and timing of the chelator administration post exposure to radionuclides are warranted.
authors.affiliation: Battelle, Pacific Northwest Division, Richland, WA 99352, USA. tatiana.levitskaia@pnl.gov
authors.forename: Tatiana G
authors.initials: TG
authors.lastname: Levitskaia
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Creim
authors.forename: Terry L
authors.initials: TL
authors.lastname: Curry
authors.forename: Teresa
authors.initials: T
authors.lastname: Luders
authors.forename: James M
authors.initials: JM
authors.lastname: Peterson
authors.forename: Karla D
authors.initials: KD
authors.lastname: Thrall
authors.forename: Barry
authors.initials: B
authors.lastname: Levinson
mesh_terms: D000818:Animals; D002586:Cesium / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D003035:Cobalt / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D007276:Injections, Intraventricular; D007495:Iridium / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D008297:Male; D010865:Pilot Projects; D011834:Radiation Monitoring / Q000379:methods*; D011868:Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D018570:Risk Assessment / Q000379:methods; D013324:Strontium / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D014018:Tissue Distribution
chemical_list: D011868:Radioisotopes; D002586:Cesium; D003035:Cobalt; D007495:Iridium; D013324:Strontium