Search

Arylalkylidenebisphosphonates labeled with nca [¹²⁵I or ¹³¹I] 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[^125,131I]-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.

ROMPgel-supported triphenylphosphine was synthesized in three steps (67%) from norbornadiene, 4-bromoiodobenzene, and chlorodiphenylphosphine. The supported reagent has a high loading (2.5 mmol/g) and favorable swelling properties in organic solvents. It has been utilized for the conversion of alcohols to halides, the reduction of ozonides, and the isomerization of α,β-acetylenic esters and in the Staudinger reaction. In general, filtration of the resin from the reaction mixtures and evaporation gave the corresponding products in high yield and purity.