title: Metal-ion speciation in blood plasma incorporating the bisphosphonate, 1-hydroxy-4-aminopropilydenediphosphonate (APD), in therapeutic radiopharmaceuticals.
abstract: In the quest for more effective pain palliation radiopharmaceuticals for metastatic bone cancer, this paper relates results obtained with 166Ho complexed to the bone-seeking bisphosphonate, 1-hydroxy-4-aminopropililydenediphosphonate (APD). APD is itself a bone cancer pain palliation agent and this work was therefore driven by the idea that the energetic beta-particle emitter, 166Ho, coupled with APD could afford a highly effective radiopharmaceutical in the treatment of bone cancer. Complex-formation constants for important blood plasma metal-ions were measured by potentiometry or polarography at 37 degrees C and I = 150 mmol dm-3. The latter technique was used for systems where precipitates formed at ligand-to-metal ratios appropriate for potentiometry. For trivalent lanthanides, neither electrochemical technique could be used. Animal tests showed that the 166Ho-APD complex was taken up primarily by the liver due to precipitation or colloid formation.
authors.affiliation: Atomic Energy Corporation of South Africa, Pretoria, South Africa.
authors.forename: J R
authors.initials: JR
authors.lastname: Zeevaart
authors.forename: N V
authors.initials: NV
authors.lastname: Jarvis
authors.forename: W K
authors.initials: WK
authors.lastname: Louw
authors.forename: G E
authors.initials: GE
authors.lastname: Jackson
authors.forename: I
authors.initials: I
authors.lastname: Cukrowski
authors.forename: C J
authors.initials: CJ
authors.lastname: Mouton
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D004164:Diphosphonates / Q000737:chemistry* / Q000627:therapeutic use*; D006695:Holmium / Q000097:blood*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000097:blood / Q000627:therapeutic use; D009943:Organophosphorus Compounds / Q000097:blood / Q000627:therapeutic use; D010166:Palliative Care; D000077268:Pamidronate; D010215:Papio; D011199:Potentiometry; D019275:Radiopharmaceuticals / Q000097:blood / Q000138:chemical synthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013324:Strontium / Q000097:blood / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D019275:Radiopharmaceuticals; C106065:holmium ethylenediaminetetramethylenephosphonate; C061972:samarium Sm-153 lexidronam; C025700:strontium chloride; D000077268:Pamidronate; D006695:Holmium; D013324:Strontium