title: Metal-ion speciation in blood plasma incorporating the tetraphosphonate, N,N-dimethylenephosphonate-1-hydroxy-4-aminopropilydenediphosphonate (APDDMP), in therapeutic radiopharmaceuticals.
abstract: In a quest for more effective radiopharmaceuticals for pain palliation of metastatic bone cancer, this paper relates results obtained with 166Ho and 153Sm complexed to the bone seeking phosphonate, N,N-dimethylenephosphonate-1-hydroxy-4-aminopropylidenediphosphonate (APDDMP). APDDMP is synthesised from the known bone cancer pain palliation agent 1-hydroxy-3-aminopropylidenediphosphonate (APD) and was complexed to lanthanide trivalent metal ions. This work is performed to utilise the idea that the energetic beta-particle emitter, 166 Ho, coupled with phosphonate ligands such as APD and APDDMP could afford a highly effective radiopharmaceutical in the treatment of bone cancer. Complex-formation constants of APDDMP with the important blood plasma metal-ions, Ca2+, Mg2+, and Zn2+ and the trivalent lanthanides Ho3+ and Sm3+ were measured by glass electrode potentiometry at 37 degrees C and I = 150 mM. Blood plasma models were constructed using the computer code ECCLES and the results compared with those gathered from animal tests. The 166Ho-APDDMP complex was found to have little liver or bone uptake while 153Sm-APDDMP had a moderate bone uptake. This was primarily due to the high affinity of APDDMP for Ca(II). Clinical observations could be explained by the blood plasma modelling.
authors.affiliation: Radiochemistry, South African Nuclear Energy Corporation (Ltd.), Pretoria. radchem@aec.co.za
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
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy; D001842:Bone and Bones / Q000378:metabolism; D004164:Diphosphonates / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D006695:Holmium / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D010215:Papio; D011522:Protons; D011868:Radioisotopes; D019275:Radiopharmaceuticals / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D012493:Samarium / Q000737:chemistry
chemical_list: D018712:Analgesics, Non-Narcotic; D004164:Diphosphonates; D008024:Ligands; C419686:N,N-dimethylenephosphonate-1-hydroxy-4-aminopropilydenediphosphonate; D011522:Protons; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D012493:Samarium; D006695:Holmium