title: Studies on the synthesis and biological properties of non-carrier-added [(125)I and (131)I]-labeled arylalkylidenebisphosphonates: potent bone-seekers for diagnosis and therapy of malignant osseous lesions.
abstract: Arylalkylidenebisphosphonates labeled with nca [(125)I or (131)I] have been synthesized and their biological function investigated. The label was attached to the aromatic group in high yield and under mild conditions by means of iododesilylation. The bone affinities of the radioactive compounds were investigated in normal Balb/C mice. The compound 1-hydroxy(m-iodo[(125,131)I]-phenylethylidene)-1,1-bisphosphonate was found to possess superior bone affinity compared to others, and its in vivo deiodination was insignificant. The uptake in femur 24h after injection was 850 +/- 265% and 986 +/- 118% of injected dose per gram tissue times gram body weight in mice and rats, respectively. The therapeutic potential of the compound was investigated in two tumor models in athymic (nude) rats, one model for mixed lytic/sclerotic metastatic bone-lesions originating from breast cancer and the other model simulating osseous osteosarcoma. The effects in these models compare favorably to those observed for established treatment modalities. The experiments demonstrate that radioiodinated bisphosphonates may have a potential for diagnosis and therapy of malignant osseous lesions.
authors.affiliation: Department of Chemistry, University of Oslo, Norway.
authors.forename: Erik
authors.initials: E
authors.lastname: Arstad
authors.forename: Per
authors.initials: P
authors.lastname: Hoff
authors.forename: Lars
authors.initials: L
authors.lastname: Skattebøl
authors.forename: Arne
authors.initials: A
authors.lastname: Skretting
authors.forename: Knut
authors.initials: K
authors.lastname: Breistøl
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001859:Bone Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D004164:Diphosphonates / Q000138:chemical synthesis* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000188:drug therapy / Q000401:mortality; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D011923:Rats, Nude; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals