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Results for “Diphosphonates”

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PubMed1986

99mTc-methylene diphosphonate uptake by ossifications and calcifications of non-osseous metastatic tumors.

Two cases of extra-osseous uptake of 99mTc-methylene diphosphonate (MDP) by non-osseous metastatic tumors are reported. One was a metastasis with ossification in the abdominal wall from carcinoma of the sigmoid colon and the other was a metastasis with calcification from an ovarian carcinoma. The mechanism of extra-osseous uptake of 99mTc-MDP is discussed. Bone scintigraphy can be a potential means to assess tumor spread with ossifications and calcifications.

Abdominal Neoplasms↗

PubMed1993

Reversible depletion of synovial lining cells after intra-articular treatment with liposome-encapsulated dichloromethylene diphosphonate.

We studied the depletion and repopulation of synovial lining cells in mice. A single intra-articular injection of liposomes encapsulating the drug dichloromethylene diphosphonate (CL2MDP) in the mouse knee joint caused selective elimination of synovial lining cells. Depletion of cells occurred within a few days as evidenced by light microscopic, electronmicroscopic and immunohistochemical studies. Maximal depletion was seen on day 7. Repopulation was observed in the following weeks, starting at the bone side of the joint. Until day 30, full recovery (60% recovery) was not observed in the lining lying adjacent to the dermis. Side effects on cartilage metabolism, such as inhibition of proteoglycan synthesis or degradation of proteoglycans from the matrix was minor but significant, 1 and 2 days after liposome treatment but thereafter full recovery was observed. Selective elimination of lining cells from the joint enabled us to study the in vivo role of these cells in the onset and subsequent pathology of experimental arthritis. An immune-complex-mediated experimental arthritis elicited in lining cell depleted joints that had received CL2MDP-liposomes 7 days earlier prevented inflammation as compared to controls.

Animals↗

PubMed1990

Isolated ectopic lung uptake of technetium 99m methylene diphosphonate on bone scintigraphy in primary amyloidosis.

Pulmonary deposition of technetium 99m methylene diphosphonate was found on a bone scan of a patient with undiagnosed primary AL amyloidosis. Unusual clinical manifestations during the course of the disease led to a post-mortem diagnosis. The mechanisms for pulmonary and other ectopic soft tissue bone scan tracer depositions, as well as their significance in the diagnosis of amyloidosis, are discussed.

Aged↗

PubMed1995

Clinical significance of technetium-99m methylene diphosphonate myocardial uptake: association with carcinoma of the prostate.

Benign myocardial uptake of technetium-99m labelled phosphates, not related to cardiac or metabolic disorders, has been documented except in the case of 99mTc-methylene diphosphonate (MDP). The aim of this study was to assess the frequency of myocardial uptake and its possible association with malignant tumours in general and prostatic carcinoma in particular. We reviewed bone scintigrams performed with either 99mTc-hydroxydiphosphonate (HDP) or 99mTc-MDP over a period of more than 2 years for all patients with prostatic carcinoma and a matching group of patients suffering from other malignant and non-malignant disorders. A total of 965 scintigrams of 812 patients (males = 559, females = 253; age range 50-91 years, average age 69.2 years) were reviewed. Increased myocardial uptake was detected in 19 scintigrams (MDP = 13, HDP = 6) of 18 patients (17 males, one female). Most of the male patients with increased myocardial uptake had prostatic carcinoma (13/17) and were over 80 years of age (12/17). All patients were free of any cardiac or noncardiac disorder that might account for such uptake. When scintigraphy was repeated in the same patient, the uptake of 99mTc-HDP was more diffuse and of higher grade than that of 99mTc-MDP. "Benign" myocardial uptake of 99mTc-MDP is more common than previously thought. Although uptake of radiophosphates is attributed to asymptomatic atherosclerotic changes associated with old age, a strong association with prostatic carcinoma exists which may indicate variations in the bone: soft tissue affinity of different MDP complexes.

Aged↗

PubMed1980

Extraosseous uptake of 99mtechnetium methylene diphosphonate: neuroblastoma or radiation therapy.

A child with a ganglioneuroblastoma and tumor uptake of 99mtechnetium methylene diphosphonate (99mTc-MDP) is presented. After surgical removal of an encapsulated tumor and radiation therapy, an interval bone scan demonstrated the same presurgical abnormality. Awareness of abnormal uptake of 99mTc-MDP in irradiated renal tissue prevents interpreting radiation nephritis as recurrent tumor.

Bone Neoplasms↗

PubMed1990

Soft-tissue uptake of 99mTc-diphosphonate and 99mTc-pyrophosphate in amyloidosis.

This study describes the results of scintigraphy with 99mTc-labeled methylene-diphosphonate (99mTc-MDP) and pyrophosphate (99mTc-PYP) as a noninvasive test for the distribution of organ involvement in five different types of amyloidosis. Scintigraphy with 99mTc-labeled phosphates appeared to be a sensitive noninvasive screening test for the extent and the distribution of organ involvement in systemic AA and systemic AL amyloidosis as well as in local bronchial amyloid, local dermal amyloid, and familial amyloidotic polyneuropathy. Echocardiography, however, was more sensitive for demonstrating cardiac involvement in systemic amyloidosis than 99mTc-MDP or 99mTc-PYP scintigraphy. 99mTc-MDP images showed a better contrast than 99mTc-PYP images, although there was no difference in the extent or the intensity of soft-tissue uptake.

Adult↗

PubMed1991

Re-evaluation of the specificity of adenylyl (beta,gamma-methylene)diphosphonate as a substrate for adenylate cyclase.

The conversion of the ATP-analogue adenylyl(beta,gamma-methylene)diphosphonate (AMPPCP) to cyclic AMP by adenylate cyclase of rat liver membranes was demonstrated using a radioimmunoassay for cyclic AMP. The conversion was only insignificantly lower than with adenylylimidodiphosphate (AMPPNP), another ATP-analogue which is usually used in the histochemical adenylate cyclase assay. The unspecific phosphate production was lower with AMPPCP as compared to AMPPNP. Therefore AMPPCP is considered to be a more suitable substrate for the histochemical assay. Unspecific phosphate deposition in the histochemical assay was due to ATP:pyrophosphatase activity and could be significantly inhibited by 1 mM NAD. However, a residual phosphate deposition due to cleavage of NAD could not be suppressed. Adenylate cyclase activity could be markedly activated by 5 x 10(-5) M forskolin, an activator of the catalytic subunit of the enzyme, and inhibited by 1 mM 2'5'-dideoxyadenosine, a specific inhibitor of adenylate cyclase. Adenylate cyclase was localized predominantly in the sinusoidal part of the plasma membrane, while ATP-pyrophosphatase seemed to be restricted to the canalicular part. It is concluded that at least three parallel assays are necessary for routine histochemical demonstration of adenylate cyclase, namely (1) basal activity (2) activation by forskolin and (3) inhibition by 2'5'-dideoxyadenosine, to demonstrate a specific enzyme reaction.

1-Methyl-3-isobutylxanthine↗

PubMed1996

Age-related changes in the global skeletal uptake of technetium-99m methylene diphosphonate in healthy women.

A short-term evaluation of global skeletal uptake (GSU) of technetium-99m methylene diphosphonate (MDP) was performed in 40 healthy female subjects with a wide age range in order to investigate the clinical performance of the technique and to detect the age-related changes in bone turnover. The results obtained were compared with measurements of the main biochemical markers of skeletal metabolism. We found that GSU increases progressively with age, independently of concomitant changes in renal function; significant correlations with biochemical markers of bone formation were also found. Therefore, the method appears to provide useful information concerning the bone turnover rate, and is also applicable to elderly people owing to its simplicity.

Adult↗

PubMed1990

Diffuse increase in renal uptake of technetium 99m methylene diphosphonate in association with disseminated cholangiocarcinoma.

A 48-year-old woman presented with disseminated cholangiocarcinoma and diffuse joint pain. A technetium 99m methylene diphosphonate bone scan revealed no bony abnormality, but intense bilateral renal uptake was seen. There was temporary renal impairment following imaging, but the cause of this is uncertain. An association between cholangiocarcinoma and 'hot kidneys' on bone imaging scanning has not been previously reported.

Adenoma, Bile Duct↗

PubMed1977

Ethane-1-hydroxy-1, 1-diphosphonate (EHDP) effects on incorporation and accumulation of osteoclast nuclei.

Male rats weighing 100 g were injected with vehicle (control group), 0.4 or 4.0 mg/kg/day of ethane-1-hydroxy-1,1-diphosphonate (EHDP). Beginning after 6 days of EHDP treatment all rats received six subcutaneous injections of 3H-thymidine at 8 h intervals. The multiple labeling index of autoradiographically defined labeled cells was determined for the osteoprogenitor cells of the primary spongiosa of the proximal tibial metaphysis. The osteoclasts in the proximal tibial metaphisis were assayed for population parameters and incorporation of labeled nuclei at sequential intervals after the administration of 3H-thymidine. After 6 days of EHDP pre-treatment the multiple labeling index of the osteoprogenitor cells was reduced with 4.0 mg/kg/day dose of EHDP. At the beginning of the experimental kinetic sampling period, after the 6 days of EHDP pre-treatment, EHDP treatment resulted in significant increases in the numbers of osteoclasts, nuclei per osteoclast profile, and total osteoclast nuclei. During the sampling period, the 4.0 mg/kg/day dose of EHDP caused further increases in the number of total osteoclasts. EHDP treatment caused a marked increase in the rate of incorporation and accumulation of 3H-thymidine-labeled nuclei in osteoclasts. Thus, EHDP causes an accelerated rate of osteoclast production from percursor cells in spite of its ability to slow bone resorption. Although the origin of osteoclast nuclei is not clear, the kinetic data from this study suggests that osteoclast nuclei are not arising from osteoprogenitor cells or osteocytes in the EHDP-treated animals.

Animals↗

PubMed1993

Chronic intoxication by ethane-1-hydroxy-1,1-diphosphonate (EHDP) in a child with myositis ossificans progressiva.

A child with myositis ossificans progressiva was treated for 8 years with ethane-1-hydroxy-1,1-diphosphonate (EHDP) 30-40 mg/kg per day. Latterly he complained of severe, progressive bone and joint pain which made standing and walking almost impossible. A radiographic skeletal survey showed diffuse ricket-like lesions. Withdrawal of EHDP therapy produced substantial improvement in his general condition as well as in the radiographic appearance of the bones. Multiple exostoses were observed in this case and, particularly those around the knees, presented a peculiar morphology. This supports the theory that exostoses originate from a defect of metaphyseal modelling.

Adolescent↗

PubMed1977

An in vitro and in vivo investigation of mellitate and ethane-1-hydroxy-1,1-diphosphonate in calcium phosphate systems.

Comparisons of mellitate (MA) and ethane-1-hydroxy-1,1-diphosphonate (EHDP) have been carried out in studies of enamel etching, calcium phosphate crystal growth and animal calculus deposition. In enamel etch studies at pH 5, 6, or 7 and after treatment times of 5 or 170 min, EHDP was less damaging to enamel surfaces than MA as determined by scanning electron microscopy, grazing angle electron diffraction, and quantitative etch solution analyses. Both MA and EHDP inhibited hydroxyapatite crystal growth, although EHDP was more effective than MA. The formation of a tricalcium mellitate surface phase is suggested as the basis of the MA crystal growth effect on apatite. Both MA and EHDP also inhibited rat calculus formation, but EHDP was more effective than MA. The relation between crystal growth inhibition, surface phase solubility, and anti-calculus activity is discussed and a generalized principal for determining an effective inhibitor of calculus is suggested.

Animals↗

PubMed1977

Changes in red cell, plasma, inulin, and total water compartments in rat femurs. Comparison of vitamin D deficiency and diphosphonate induced rickets.

The vascular space, as measured with the use of 99m-technetium-labelled red cells and 131I-serum albumin, as well as the 14C-inulin and 3H2O fluid compartments were measured in rats which had been made rachitic by the use of a low phosphate vitamin D-deficient diet. A similar group of rachitic animals fed vitamin D2 50 IU, 5 and 3 days prior to sacrifice and a weight-matched control group were also studied. The same spaces were measured in rats made rachitic by daily s.c. injections of ethane-1-hydroxy-1,1-diphosphonate (EHDP) for 4 weeks and a weight-matched saline injected control group. Findings indicated that the red cell and RISA spaces were unchanged in the untreated D-deficient group as compared to controls but increased after being repleted with vitamin D. By contrast, the vascular space was depressed in the EHDP-treated group. The water content was elevated in D-deficient rickets returning towards normal on healing, whilst both inulin and water spaces were increased in the EHDP-treated animals. Thus, while the extravascular space reflected the presence of osteoid, the vascular space depended on cellular turnover and the process of mineralization.

Animals↗

PubMed1980

Binding of the bone-seeking agent 99mTc-1-hydroxyethylidene-1,1-diphosphonic acid to cartilage and collagen in vitro and its stimulation by Er3+ and low pH.

The bone-seeking agent 99mTc-labeled 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP) unexpectedly binds to particles of human articular cartilage as well as cortical bone in vitro. Collagen also sequesters this compound, suggesting that collagen contributes to the uptake of 99mTc-HEDP by cartilage and bone. Particles of the bone mineral calcium hydroxyapatite also bind 99mTc-HEDP in vitro. Pretreatment of particles with Er3+ stimulates binding in each case. Lowering the pH of incubation to pH 2 has this effect for bone, cartilage, and collagen, but not for calcium hydroxyapatite. Mechanisms additional to the simple ionic attraction between the phosphonate groups of HEDP and metal cations such as Ca2+ are responsible for the uptake of 99mTc-HEDP by body tissues.

Adult↗

PubMed1975

Ethane-1-hydroxy-1, 1-diphosphonate (EHDP). Effects on growth and modeling of the rat tibia.

One hundred gram male Sprague-Dawley rats were divided into groups which were injected daily for 10 or 30 days with vehicle (control group), 0.2, 0.4, 2.0, or 10.0 mg ethane-1-hydroxy-1,1-diphosphonate (EHDP)/kg/day. The proximal tibial metaphysis and epiphysis were assayed for changes in percentage of hard tissue and bone formation factors. Knowing these, information about hard tissue resorption was deduced. After ten or thirty days treatment with 2.0 or 10.0 mg EHDP/kg/day, there was an increase in percentage of hard tissue. This was due to a decrease in bone formation with a greater decrease in hard tissue resorption. Furthermore, after thirty days treatment with 0.2 and 0.4 mg EHDP/kg/day, there was an increase in percentage of hard tissue, which was due to a decrease in resorption with no change in formation. Ultrastructural studies on osteoclasts from EHDP-treated rats showed a general decrease in their vacuolization and amount of organelles as dosage of EHDP increased. Histologic findings suggest that EHDP is similar to fluoride in the way in which it depresses hard tissue resorption.

Animals↗

PubMed1975

The comparative effects of vitamin d deficiency and ethane-1-hydroxy-1,1-diphosphonate administration on the histology and glycolysis of chick epiphyseal and articular cartilage.

A comparison has been made between the effect of a vitamin D--deficient diet and treatment with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) on the morphology of chick epiphyseal cartilage and on the production of lactate in vitro by epiphyseal and articular cartilage. The cell populations in the growth plate were different following the two treatments. Vitamin D deficiency was characterized by an increase in proliferating cells, with a relative paucity of hypertrophic cells; EHDP treatment was characterized by an increase in hypertrophic cells. When similar cell types were compared, neither treatment changed lactate production from the control value. This stresses the need to correlate the morphology of cell types with their metabolic function. The present results indicate that the major effect of vitamin D deficiency in the chick is to block the differentiation of proliferating to hypertrophic cells. In contrast, EHDP may act by inhibiting calcification directly. Even though EHDP at the doses used is known to interfere with the production of 1,25-dihydroxycholecalciferol there is no block to cell differentiation under EHDP similar to that seen in dietary deficiency of vitamin D.

Animals↗

PubMed2003

Effect of technetium-99 conjugated with methylene diphosphonate on IgM-RF, IgG-RF and IgA-RF.

To explore the effect of technetium-99 conjugated with methylene diphosphonate (99 TcMDP) on IgM-RF, IgG-RF and IgA-RF (RFs), 47 cases were selected for study, including 33 patients with rheumatoid arthritis (RA) and 15 patients with joint pain/arthritis. After 99Tc-MDP for drips model being given to the patients by intravenous drip 0.2 g daily for 5 days, the injection A and B models of 99Tc-MDP were used to the patients by intravenous injection one set daily for 10 days, that was one course of treatment. The next course started after 10 days. Each case used it from 2 to 4 courses of treatment. The RFs in serum were determined by the method of enzyme-linked immunoabsorption assay (ELISA) before and after 2 and 4 courses of treatment. In the patients with RA, the concentrations of IgM-RF were 296.2 +/- 108.4 IU/ml, 189.5 +/- 92.3 IU/ml and 107.8 +/- 72.5 IU/ml; the concentrations of IgG-RF were 325.6 +/- 126.2 IU/ml, 209.7 +/- 98.2 IU/ml and 160.2 +/- 80.8 IU/ml; the concentrations of IgA-RF were 330.4 +/- 136.3 IU/ml, 210.7 +/- 89.2 IU/ml and 148.8 +/- 72.2 IU/ml before and after 2 and 4 courses of treatment, respectively. The concentrations of the above RFs were significantly lower after 2 and 4 courses than those before treatment (P < 0.05 and P < 0.01). There was no significant difference in RFs concentrations in the patients with joint pain/arthritis before and after use of 99Tc-MDP. In the patients with positive RFs before treatment, the RFs concentrations were decreased significantly after 2 and 4 courses of treatment (P < 0.05 and P < 0.01). There was no obvious change of RFs concentrations in the patients with negative RFs after treatment of 99Tc-MDP. It was concluded that 99 Tc-MDP could obviously reduce the abnormally high concentrations of RFs, but not influence the normal RFs, which indicated that 99Tc-MDP has an important effect on controlling the activities of RA.

Adult↗

PubMed2004

Superimposed dual-isotope SPECT using 99mTc-hydroxymethylene diphosphonate and 201Tl-chloride to assess cartilage invasion in laryngohypopharyngeal cancer.

OBJECTIVE: Cartilage invasion in laryngohypopharyngeal cancer has a significant impact on the choice of treatment modality and outcome of the disease. We examined invasion of cartilage in laryngohypopharyngeal cancer by simultaneous bone and tumor dual-isotope SPECT using 99mTc-hydroxymethylene diphosphonate and 201Tl-chloride. METHODS: Early and delayed simultaneous bone and tumor dual-isotope SPECT were performed on 19 patients with laryngohypopharyngeal cancer. Dual-isotope SPECT images were superimposed to project tumor location from tumor SPECT onto the osseous structures shown by bone SPECT. The presence or absence of cartilage invasion was evaluated histopathologically or by radiological studies such as CT and/or MRI. RESULTS: Histopathological or radiological examination of the cartilage revealed invasion in 5 patients and no invasion in 14 patients. The results of both early and delayed dual-isotope SPECT were exactly the same. Using dual-isotope SPECT, the sensitivity, specificity, and accuracy in detecting cartilage invasion by laryngohypopharyngeal cancer were: 80% (4/5), 92.9% (13/14), and 89.5% (17/19), respectively. CONCLUSIONS: Results of the present study suggest that superimposed early bone and tumor dual-isotope SPECT images may be sufficient for the diagnostic evaluation of cartilage invasion by laryngohypopharyngeal cancer. Superimposed dual-isotope SPECT imaging is a useful technique in the evaluation of cartilage invasion in laryngohypopharyngeal cancer.

Aged↗