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PubMed1977

Positive (99mTc) diphosphonate and 67 Ga-citrate scans in ameloblastoma: case report.

Technetium-99m-diphosphonate scintigrams and 67Ga citrate bone scans were performed in a patient with known ameloblastoma of the right mandible. The tumor concentrated both radionuclides avidly. The lesion was larger on the gallium scans, presumably due to inflammation of adjacent soft tissue and to poorer instrument resolution for 67Ga than for technitium. If a single radionuclide is to be selected for evaluating the extent of tumor in ameloblastoma, the bone-imaging agent is preferable.

Adult↗
PubMed1997

Topological structure activity analysis of diphosphonates in the elimination of radionuclides from body.

The effectiveness of a series of diphosphonates in the elimination of radionuclides from rat was analyzed by means of topological structure and activity relations. It is possible to compute some numbers or indexes characteristic of the topological structure of a molecule. The Wiener Index which measures the ramification of a molecule has been chosen. An attempt was made to correlate the effectiveness of the molecules tested in removing plutonium from the organism to their Wiener Index. Only unprotected molecules i.e in free acidic form fitted the correlation. LICAM (C) and DTPA were used as reference molecules to control these results. The fact that LICAM (C) well fitted the relation and that DTPA did not are discussed, as are some general requirements for a new molecule to be effective.

Animals↗
PubMed1976

Diphosphonate treatment of Paget's disease.

Ethane-1-hydroxy-1, 1-diphosphonate (EHDP) was administered in a dose of 20 mg/kg/d to 21 patients with symptomatic Paget's disease. All patients were treated for 6 months and then followed for an additional 6 months. There was a striking decline in serum alkaline phosphatase and urinary hydroxy-proline excretion observed after 3 months of therapy which was not significantly improved in the succeeding 3 months. Concomitantly there was marked improvement in clinical symptoms and bone scans. Following cessation of therapy, continued biochemical and clinical evidence of remission persisted. Several patients on repeat treatment with EHDP appeared to respond promptly. Side effects were minimal except for a possibly related osteomalacia and increased incidence of pathologic fractures.

Aged↗
PubMed1976

Pulmonary calcification in chronic renal failure: use of diphosphonate scintiscan as a diagnostic tool.

A patient with end-stage renal failure on maintenance hemodialysis for fifty-five months presented with signs and symptoms of cardiorespiratory failure and chest X-ray evidence of cardiomegaly and persistent bilateral nodular lung densities. A lung scan employing a bone seeking radionuclide, 99 Tc Diphosphonate, revealed active uptake in all areas corresponding to the X-ray densities. It was concluded that these densities represented active calcification. Thus, a diagnosis of pulmonary calcification was established without the need to resort to lung biopsy. It is suggested that bone-seeking radionuclides may be employed effectively to help establish an early diagnosis of pulmonary calcification especially in high risk dialysis patients.

Adult↗
PubMed1999

Granulocyte-macrophage colony-stimulating factor protects dendritic cells from liposome-encapsulated dichloromethylene diphosphonate-induced apoptosis through a Bcl-2-mediated pathway.

Liposome-encapsulated dichloromethylene diphosphonate (L-MDP) has been used for depleting cells of the monocyte-macrophage lineage. We have undertaken this study to investigate whether dendritic cells are susceptible to this liposome-encapsulated compound. Dendritic cells were cultured in the presence of L-MDP and further processed for apoptosis detection. The highly characteristic DNA cleavage into oligonucleosome-sized fragments, incorporation of biotinylated dUTP into DNA strand breaks and the typical ultrastructural features of apoptosis were evident in dendritic cells exposed to the drug. More importantly, we demonstrated that granulocyte-macrophage colony-stimulating factor protects dendritic cells not only from apoptosis induced by the exogenous compound but also from spontaneous apoptosis. Western blot analysis revealed that this protection was tightly correlated with the activation of a Bcl-2-mediated pathway. Regulation of the apoptotic threshold of dendritic cells will be advantageous for the generation of new insights in immunotherapy.

Analgesics, Non-Narcotic↗
PubMed1987

Histomorphometric changes of osteosarcoma after chemotherapy. Correlation with 99mTc methylene diphosphonate functional imaging.

An investigation to correlate histologic changes in 12 osteosarcoma specimens from patients undergoing chemotherapy was performed using functional images of regional 99mTc methylene diphosphonate (MDP) plasma clearance rates assessed from dynamic bone scintigraphies taken during chemotherapy. Residual tumor cell viability was determined by microscopic examination of multiple thin sections from surgical specimens and quantitated by histomorphometry. Regions that showed decreases in 99mTc MDP plasma clearance of more than 20% were associated with areas of necrotic tumor, and regions that showed absent decline or increasing clearance rates were associated with high residual cell viability and incomplete response to chemotherapy. Therefore, functional bone scintigraphy allows an objective presurgical assessment of tumor response to chemotherapy.

Adolescent↗
PubMedDate not supplied

Periarticular uptake of 99mtechnetium diphosphonate in psoriatics: correlation with cutaneous activity.

The periarticular uptake of 99mtechnetium-labeled diphosphonate (99mTcDp) was compared in 12 patients hospitalized for psoriasis and in 12 hospitalized for other dermatoses not associated with arthropathy. The 12 patients with psoriasis had recent onset disease of less than 5 years duration; neither group had historical or clinical evidence of arthritis. All psoriatics had markedly abnormal scans with symmetrically increased periarticular uptake about the imaged joints. None of the controls had similar findings. In 4 patients scanned with 99mtechnetium-pertechnetate within 24 hours of their 99mTcDP scan, no evidence of inflammatory synovitis was found. Three of these patients were serially imaged with 99mTcDP at intervals of 2 weeks to 3 months after their initial study, when obvious clinical improvement in their psoriasis was apparent. Improvement in the radionuclide joint images was demonstrated in some of the patients, but none reverted to normal during the study period. In light of recent evidence for the preferential binding of 99mTcDP to immature collagen, it is suggested that psoriasis may represent a generalized, but uncharacterized, collagen disorder present in bone as well as skin, linking the cutaneous disease with the potential for arthropathy.

Adult↗
PubMed1991

Selective depletion of liver and splenic macrophages using liposomes encapsulating the drug dichloromethylene diphosphonate: effects on antimicrobial resistance.

The current results provide direct evidence for a role of tissue macrophages (M phi) in natural immunity and support the use of immunomodulators to enhance antiviral resistance in immunocompromised individuals. In this study, macrophages (M phi) in the spleen and liver were eliminated by intravenous (i.v.) injection of the drug dichloromethylene diphosphonate (DMDP) encapsulated in liposomes. The effect of this depletion system on peritoneal M phi, peripheral blood leukocytes, splenic natural killer (NK) activity, and natural and immunomodulator-induced host resistance was then assessed. Barrier-maintained CD-1 female mice were inoculated i.v. either with DMDP liposomes, free liposomes (containing no DMDP), or saline on day -2 or on days -3 and -1 before cell population analysis or infection. Single or double treatment with DMDP liposomes had no effect on peritoneal M phi as indicated by no changes in total number, differential counts, or ectoenzyme patterns. Double treatment with DMDP liposomes caused a marked leukocytosis in blood, primarily of lymphocytes and polymorphonuclear leukocytes (PMN), and a transient depression of spontaneous and interferon-inducible splenic NK activity. The effects on host resistance to i.v. infection with Listeria monocytogenes or herpes simplex virus type 2 (HSV-2) indicated that i.v. treatment with DMDP liposomes significantly reduced natural resistance to these microorganisms as evidenced by increased mortality and decreased median survival time. When DMDP liposomes-treated mice were given the immunomodulator maleic anhydride divinyl ether copolymer (MVE-2) intraperitoneally the day before infection with HSV-2, the immunosuppressive effect of DMDP liposomes treatment was significantly reversed.

Adjuvants, Immunologic↗
PubMed1986

Prevention of ectopic bone formation by local application of ethane-1-hydroxy-1,1-diphosphonate (EHDP): an experimental study in rabbits.

This report shows that ectopic bone formation, a serious problem in orthopedic surgery, can be controlled in an animal model by local application of EHDP (disodium-ethane-1-hydroxy-1,1-diphosphonate). The results might be particularly pertinent to the clinical problem of preventing the recurrence of ectopic bone after surgical excision. Male New Zealand white rabbits were treated with immobilization and intermittent passive manipulation of the right knee. The treatment caused bone formation in the quadriceps muscle, which was visible on radiographs after 3 weeks. In this model, the effect of methacrylate implants containing EHDP was studied. A concentration of 16 g EHDP/100 g methacrylate inhibited bone formation in experimental cortical defects. Release of radiolabeled EHDP was studied in an in vitro system. The release of the drug was approximately 20 mg/day and implant initially, decreasing to about 0.1 mg/day/implant after 30 days. Standardized implants containing 16 g EHDP/100 g were then surgically attached to the femur, and the ectopic bone formation created by immobilization and intermittent manipulation was compared with that in rabbits treated with implants but without EHDP. The ectopic bone was measured from lateral and frontal radiograms and from radiograms of serial transverse sections of the thigh. We found that the EHDP implants were capable of preventing major ectopic bone formation in all cases, whereas all rabbits with an implant containing no EHDP had substantial ectopic bone formation at the end of the experiment. There was no difference between groups in the relative amount of cartilage, connective tissue, and normal bone. We conclude that local administration of EHDP may be a useful method for prevention of ectopic bone formation under the conditions and time employed.

Animals↗
PubMed1986

Localization of technetium-99m methylene diphosphonate in bone using microautoradiography.

Technetium-99m methylene diphosphonate ([99mTc]MDP) is the most widely used bone-scanning agent today. In order to determine the precise bone locus of 99mTc corresponding to the delayed bone scan image, and to test the potential clinical use of this agent in enhancing the information obtained by bone scan, we employed [99mTc]MDP in this microautoradiographic study of normal bone and bone reparative tissue. Four white rabbits underwent operations in which two 1.5-mm drill holes were created in the subtrochanteric regions of both of their femora. An additional four white rabbits underwent sham operations of their femora, in which neither drilling nor periosteal injury occurred. Two rabbits were controls and did not undergo operation. After 7 days, the first two groups of rabbits were injected with [99mTc]MDP and bone scanned 2 h later. After the scans were completed, all three groups of animals were killed and their femora histologically processed for microautoradiography and routine histopathology. In the two groups that were injected with [99mTc]MDP, all bones showed the isotope to be clearly localized along mineralization fronts. The isotope was occasionally found in the substance of the osteoid, but was absent from the cytoplasm and nuclei of osteoblasts and osteocytes. Osteocytic lacunae showed the presence of isotope at their borders, but no identifiable pattern of isotope uptake was noted. Neither osteoclasts nor Howships lacunae showed isotope uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Preparation of 1-hydroxyethylidene-1,1-diphosphonic acid-intercalated layered double hydroxide and its physicochemical properties.

The intercalation of 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP), which is a drug for osteoporosis, in layered double hydroxide (LDH) was examined with the goal of developing a novel drug delivery system (DDS) of HEDP. To prevent side reactions, the intercalation reaction was carried out at 0 degrees C, and at pH 4-6. The uptake of HEDP was determined as 3.5 mmol x g(-1) of LDH, and the interlayer distance increased from 7.8 to 13 A. The HEDP-release profiles into K(2)CO(3) aqueous solution and into various buffer solutions were also examined.

Chemical Phenomena↗
PubMed1987

Controlled-release drug delivery of diphosphonates to inhibit bioprosthetic heart valve calcification: release rate modulation with silicone matrices via drug solubility and membrane coating.

Calcification (CALC) is the most frequent cause of the clinical failure of bioprosthetic heart valves (BHV) fabricated from glutaraldehyde pretreated porcine aortic valves or bovine pericardium. The present investigation describes the formulation, characterization, and the in vivo efficacy of prolonged controlled-release silicone matrices containing the anticalcification agent disodium 1,1-hydroxyethylidene diphosphonate (Na2EHDP). Controlled release of EHDP was regulated by codispersions of Na2EHDP and the less soluble salt Ca2EHDP. Prolonged and constant release rates (zero-order) were obtained by coating silicone matrices with permeable silicone membranes, which were prepared by leaching with acetone pre-embedded polyethyleneglycol. All EHDP-containing matrices (co-implanted subdermally with BHV cusps in rats) significantly inhibited BHV CALC without detectable adverse effects on bone mineral and calcium metabolism. Matrices containing Na2EHDP:Ca2EHDP ratios of 10:90 or greater with respect to Na2EHDP completely inhibited CALC. Significant inhibition of BHV CALC was also observed with prereleased matrices (5 months in vitro), thus demonstrating prolonged efficacy. It is concluded that sustained release of effective anticalcification therapy without side effects was achieved by using codispersions of calcium and sodium EHDP salts, and that a delayed and/or constant release rate of EHDP was obtained by coating reservoir-type matrices with silicone membranes that were pre-embedded with polyethyleneglycol.

Animals↗
PubMed1977

Effect of the diphosphonate EHDP on plasma inorganic phosphate and hemoglobin oxygen affinity of diabetic and healthy subjects.

The effect of oral disodium ethane-1-hydroxy-1,1-diphosphonate, EHDP (20 mg kg-1 day-1) and placebo given for 28 days on plasma inorganic phosphate (Pi) red cell 2,3-diphosphoglycerate and oxygen affinity of hemoglobin was evaluated in 14 insulin-treated diabetics and 5 healthy volunteers. EHDP significantly increased mean Pi (diabetics: 1.18 to 1.67 mmol/l, p less than 0.01, controls: 1.03 to 1.71 mmol/l, p less than 0.02) and P50 at in vivo pH of the oxyhemoglobin dissociation curve (diabetics: 25.4 to 26.6 mmHg, p less than 0.02; controls: 26.3 to 28.9 mmHg, p less than 0.02). Pi and P50 were correlated in both diabetics and in controls (p less than 0.05). 2,3-DPG increased when the diabetics were on EHDP (p less than 0.005). The study emphasizes the importance of Pi on red cell function and indicates that an elevation of Pi tends to counteract the defect in oxygen release capacity of the red cells in diabetic subjects.

Carbon Dioxide↗
PubMed1993

Usefulness of technetium-99m hydroxymethylene diphosphonate scans in localizing bone metastases of differentiated thyroid carcinoma.

Iodine-131 is uniquely able to demonstrate iodine uptake of differentiated thyroid carcinoma (DTC), but precise localization may be difficult, especially in the thorax, due to the quality of image resolution with 131I and the lack of anatomical landmarks. When bone metastases do not show radioiodine uptake bone scintigraphy can be used to detect them. We studied two groups of patients. In group 1, 15 patients with known bone metastases of DTC were treated with 3.7 GBq 131I. After 4 or 5 days, technetium-99m hydroxymethylene diphosphonate (HMDP; 740 MBq) was injected and a whole-body scan with simultaneous acquisition of 131I and 99mTc-HMDP images was carried out using a large field of view gamma camera fitted with a high-energy collimator. Technetium uptake was abnormal in 47 of 63 localizations, being increased in 29 foci, decreased in 7 and heterogeneous in 11. The superimposition of 131I and 99mTc-HMDP scans permitted an accurate localization in 80% of spine metastases and in 46% of osseous thoracic localizations, even in the presence of lung metastases. In group 2, 9 patients, who had bone pain, neurological signs or elevated serum thyroglobulin, had DTC bone metastases without iodine uptake. They received a diagnostic dose of 99mTc-HMDP 3h prior to scintigraphy with a large field of view gamma camera fitted with a low-energy collimator. Technetium uptake was abnormal in 37 of 38 localizations, being increased in 34 foci and decreased in 3. One false-negative was found in a skull metastasis. In both groups of patients, 99mTc-HMDP scans were useful.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma, Follicular↗
PubMed1991

Techetium 99m methylene diphosphonate bone scanning in osteoarthritic hands.

In this prospective study, the radiological features characteristic of osteoarthritis of the hand were compared with the radionuclide bone scan images. A total of 32 patients was assessed at 6-monthly intervals for 18 months. Microfocal radiographs were taken at each visit. The high magnification and resolution of this technique permitted direct measurement of joint space width, subchondral sclerosis, osteophyte number and area and juxta-articular radiolucency area for each joint in the hand. Four-hour technetium 99m methylene diphosphonate bone scans were taken at 0 and 12 months and the activity of tracer uptake at each joint scored. The latter was compared with each X-radiographic feature at every visit and the changes between visits analysed. The scan scores did not correlate with any of the X-radiographic features other than osteophyte size. During the study the size of growing and remodelling osteophytes increased significantly at joints with raised or increased isotope uptake.

Female↗
PubMed1994

Dose escalation study of rhenium-186 hydroxyethylidene diphosphonate in patients with metastatic prostate cancer.

Rhenium-186 hydroxyethylidene diphosphonate (186Re-HEDP) has been used for the palliative treatment of metastatic bone pain. A phase 1 dose escalation study was performed using 186Re-HEDP. Twenty-four patients with hormone-resistant prostate cancer entered the study. Each patient had at least four bone metastases and adequate haematological function. Groups of at least three consecutive patients were treated with doses starting at 1295 MBq and increasing to 3515 MBq (escalated in increments of 555 MBq). Thrombocytopenia proved to be the dose-limiting toxicity, while leucopenia played a minor role. Early death occurred in one patient (10 days after administration) without clear relationship to the 186Re-HEDP therapy. Transient neurological dysfunction was seen in two cases. Two patients who received 3515 MBq 186Re-HEDP showed grade 3 toxicity (thrombocytes 25-50 x 10(9)/l), defined as unacceptable toxicity. After treatment alkaline phosphatase levels showed a transient decrease in all patients (mean: 26% +/- 10% IU/l; range: 11%-44%). Prostate-specific antigen values showed a decline in eight patients, preceded by a temporary increase in three patients. From this study we conclude that the maximally tolerated dose of 186Re-HEDP is 2960 MBq. A placebo-controlled comparative study on the efficacy of 186Re-HEDP has been initiated.

Aged↗
PubMed1981

Uptake of 99mTc-diphosphonate in liver metastasis of an ovarium carcinoma.

A case with uptake in the liver of 99mTc-diphosphonate on scintigraphy is presented. The patient was operated on twelve years before for an ovarium carcinoma. Extensive examinations demonstrated the metastatic nature of the liver tumours. Comparison with the few cases in the literature is made.

Adenocarcinoma↗