Methylene diphosphonate

Technetium-99m medronate ( Tc methylene diphosphonate) is used as a bone imaging agent to delineate areas of altered osteogenesis. The product is formed by the addition of up to 7.4 GBq (200 mCi) of Tc pertechnetate. 

Diphosphinomethane is a valuable intermediate to form methylene diphosphonic acid by oxidation with nitric acid (see Sec. IV). The alkali salts of methyl-enediphosphonic acid offer sequestering properties and are used as detergent builders. 

X-irradiated Single Crystal of Methylene Diphosphonic Acid... 

Lucken and co-workers32 subjected a single crystal of methylene diphosphonic acid to X-irradiation. The ESR spectrum indicated that the radicals produced were those pictured in Tables 4.7 and 4.8. The spectra were analyzed as described above and the results are also summarized in the tables. The species shown in Table 4.7 is the more abundant of the two. The methylene group freely rotates at room temperature but is stationary at 77 K, where splitting from two non-equivalent protons is observed for some orientations of the crystal. 

Log A values for the analogous EtPO2 complexes are almost identical (Ref. (689)) stability constants for methylene diphosphonate complexes are considerably higher - for Ca2+ log K = 4.7. 

Complexes of beryllium with phosphonate ligands have been extensively researched, mainly by potentiometry. The ligands investigated are as follows methylphosphonate (259, 260) chloromethyl-phosphonate (259) 2-aminopropane-l-phosphonate (259) methylene-diphosphonate (130, 260, 261) hexamethylenediphosphonate (259) l-hydroxyethane-l,l-diphosphonate (261) 1,1-dimethyl-1-amino-... 

G.M. Blake, S.J. Park-Holohan, G.J. Cook, I. Fogelman, Quantitative studies of bone with the use of F-fluoride and 99mTc-methylene diphosphonate, Semin. Nucl. Med. 31(1) (2001) 28-49. 

Schenk, R., et al. Effect of ethane-l-hydroxy-1, 1-diphosphonate (EHDP) and dichlor-methylene diphosphonate (CI2 MDP) on the calcification and resorption of cartilage and bone in the tibial epiphysis and metaphysis of rats. Calc. Tiss. Res. 77, 196 (1973)... 

Until recently it has rarely been possible to definitively characterize the "mTc species present in a radiopharmaceutical formulation because of the extremely low concentrations involved. In some cases, electrophoresis has been used as a means of determining the minimum number of species present. In a recent example a methylene diphosphonate formulation for preparing a "mTc bone imaging agent was found to produce at least four different "mTc species.581 In favourable circumstances it may be possible to determine the net charge on the ionic materials present by this technique. However, such measurements require careful interpretation if erroneous conclusions are to be avoided, and they provide no detailed information relating to chemical structure.20... 

Methylene diphosphonic acid (MDPA) 1-Hydroxy ethylidene-l,l-diphosphonic acid (HEDPA)... 

FIGURE 11.3 Percent recovery of 3-(trimethylsilyl)-l-propyl- and 2-ethylhexyl-substituted methylene diphosphonic acids from glass beads at 250 bar and 60°C. 

Hyman, A. A., Chretien, D., Arnal, I and Wade, R. H. (1995). Structural changes accompanying GTP hydrolysis in microtubules Information from a slowly hydrolyzable analogue guanylyl-(a,JS)-methylene-diphosphonate. / Cell Biol. 128, 117-125. 

Mono- and Difluoro Derivatives of Methylene-diphosphonic Acid Synthesis with Perchloryl Fluoride... 

Tetraisopropyl methylene-diphosphonate Hydrogen chloride l-(4-Chlorphenyl) disulfide Sodium hydroxide... 

The 50% strength suspension of sodium hydride in oil is added, a little at a time to a solution of tetraisopropyl methylene-diphosphonate in dimethylformamide. After all has been added, the mixture is stirred, the l-(4-chlorphenyl) disulfide is then added and the whole is heated at 25°C for 6 h. The mixture is evaporated to dryness in vacuo and residue is taken up in hexane. The solution is washed with water and dried. The solvent is evaporated to dryness and the residue is chromatographed on silica column, elution being carried out with a 98 2 (v/v) mixture of methylene chloride/methanol. The obtained l-(4-chlorphenylthio)tetraisopropyl methylene-diphosphonate is then hydrolyzed with 12 N HCI for 18 h to give the l-(4-chlorphenylthio)methylene-diphosphonic acid. 

The l-(4-chlorphenylthio)methylene-diphosphonic acid are dissolved in water, containing sodium hydroxide. The solution is filtered, the methanol are then added and the mixture is left to crystallize. The precipitate is filtered off and washed with methanol and dried at 80°C in vacuo and the disodium salt of 1-(4-chlorphenylthio)methylene-diphosphonic acid is thus obtained. 

Fig. 18. Bone scan images with methylene diphosphonate (MDP). Patchy accumulation was observed in the kidney (From [22], with permission)...

This patient was the first case of ALPE in which a bone scan with 99mTc-methylene diphosphonate (MDP) showed patchy findings (see Fig. 18) (the details are given in Chap. 3, Sect. 4). Severe abdominal pain developed after skiing. He consulted our hospital under a self-diagnosis of acute pancreatitis. 

In the patients with ALPE, bone scans showed no muscular uptake of methylene diphosphonate (MDP). However, upper/lower limb muscle uptake of MDP was found in the patients with myoglobinuric acute renal failure (Fig. 75). 

Ishikawa I, Ishii H, Saito T, Yuri T, Shinoda A, Urashima S (1987) Increased patchy renal accumulation of 99mTc-methylene diphosphonate in a patient with severe loin pain after exercise. Nephron 47 29-31... 

The spectroscopic and X-ray studies of diphosphoryl adducts of diorganotin(IV) halides revealed that they possess different structures depending on the nature of organotin halide and the diphosphoryl Thus, methylene-diphosphonates and... 

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