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Results for “Diphosphonates”

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PubMed1985

[Kinetics of the interaction of methylene diphosphonic acid and inorganic pyrophosphate with DNA-dependent RNA-polymerase from calf thymus].

The kinetics of interaction of PPi and its diphosphonic analog, methylenediphosphonic acid (MDPA), with nucleoside triphosphates, DNA and Mg2+ binding sites of DNA-dependent RNA polymerase II from calf thymus was investigated. The values of apparent Km in the NTP polymerization reaction for ATP and CTP equal to 2.7 X 10(-4) and 1.8 X 10(-4) M, respectively, were determined. It was shown that MDPA and PPi competitively inhibited the RNA polymerase reaction with respect to nucleoside triphosphate. The inhibition constants (Ki) of ATP and CTP incorporation for MDPA were 2.2 X 10(-4) and 3.3 X 10(-4) M, respectively, while those of the nucleoside triphosphate incorporation for PPi were equal to 1.4 X 10(-4) and 2.0 X 10(-4) M, respectively. MDPA and PPi were incompetitive inhibitors of template (DNA) and Mn2+. A possible mechanism of inhibition of the RNA polymerase reaction by MDPA is proposed.

Animals↗

PubMed1985

[Interaction between radiopharmaceutical and therapeutic agents. The modification of the distribution of 99mTc-methylene diphosphonate by D-penicillamine].

The effect of D-penicillamine on the distribution of 99mTc-MDP was studied in male Wistar rats. There were significant activity decreases after medication in blood, kidney, lung and skeletal muscle. The activity in the skeleton was not influenced by D-penicillamine. After treatment, the liver showed a significant increase of activity. The clearance of activity not bound to the skeleton altogether accelerates after D-penicillamine medication. It is assumed that the change of kinetics is caused by a complex formation of the radiopharmaceutical and D-penicillamine. D-penicillamine possibly displaces methylene diphosphonate from the 99mTc-complex.

Animals↗

PubMed1988

Non-invasive evaluation of bone formation: measurements of serum alkaline phosphatase, whole body retention of diphosphonate and serum osteocalcin in metabolic bone disorders and thyroid disease.

Three noninvasive indices of bone formation, serum alkaline phosphatase (s-AP), 24-h whole body retention of diphosphonate (WBR), and serum osteocalcin (s-OC), the two lastnamed clearance-corrected, were compared in 121 patients with various bone disorders and in 50 patients with thyroid disease. In conditions with qualitatively normal matrix formation and mineralization, i.e. thyrotoxicosis, primary hyperparathyroidism, myxoedema and osteoporosis, the three indices deviated from average normal by about the same extent: 134%/128%/200%, 120%/113%/133%, 105%/100%/79% and 89%/86%/69%, respectively. A disproportionately marked deviation of s-AP was observed in states of abnormal matrix formation or mineralization, i.e. osteomalacia and Paget's disease: 430%/145%/282% and 348%/145%/202%, respectively. Furthermore, the formation indices correlate differently with s-calcium in hyper- and hypocalcaemic conditions. In primary hyperparathyroidism the respective r-values were 0.32/0.62/0.68, while an inverse pattern was observed in osteomalacia: -0.60/-0.51/-0.47. As very little is known about the secretion of AP and OC and their role in bone formation and mineralization, the cause(s) for the observed differences remain(s) uncertain.

Adult↗

PubMed1987

Bone turnover determined by urinary excretion of [99mTc]diphosphonate in the prediction of postmenopausal bone loss.

Bone mineral content (BMC) of the forearms was measured in 62 healthy early postmenopausal women every 3 months for 2 years to calculate the rate of bone loss. Furthermore, bone turnover was determined at one year using the urinary excretion (UE) of [99mTc]diphosphonate. UE was assessed as a diagnostic test using BMC changes as the gold standard for bone loss. The predictive value for 'accelerated bone loss' (positive test) was 0.58 and for 'non-accelerated bone loss' (negative test) 0.76. The data do not warrant the use of UE as a screening method for bone loss.

Adult↗

PubMed1985

The effect of methylene diphosphonate on the tissue distribution of gallium-67.

Nonradiolabeled methylene diphosphonate (MDP) was administered intravenously to CFW Swiss outbred female mice 2 hr prior to i.v. injection of [67Ga]citrate. The dose of MDP ranged from that usually administered for bone scanning (17.9 micrograms/kg) to 1,000 times the usual bone scan dose (17.9 mg/kg). The animals were killed 24 hr after administration of [67Ga]citrate and organ distribution determined as compared to control animals who received no MDP. At MDP doses one to ten times usual bone scan dose, the only organ showing significantly different 67Ga uptake was the lung and this difference in pulmonary uptake was accounted for by incidental pulmonary infection. At MDP doses 100 to 1,000 times usual bone scan dose, significantly altered 67Ga uptake was noted in lung, spleen, kidney, and gastrointestinal tract. The only consistent pattern of association of MDP administered dose and alteration in 67Ga uptake, however, was noted in the spleen where uptake was augmented with increased dose, and the bone where increased MDP dose depressed 67Ga uptake. Even this effect, however, was modest. It is concluded that at usual MDP dose levels used in bone imaging, no significant alterations occur in 67Ga distribution in normal mouse tissue. It is inferred that 67Ga scans performed following bone scans can be interpreted as if both radiopharmaceuticals had been administered separately.

Animals↗

PubMed1985

Distribution of 3-amino-1-hydroxypropane-1,1-diphosphonic acid in rats and effects on rat osteosarcoma.

The distribution of 14C-APD and 99mTc-APD (APD = 3-amino-1-hydroxypropane-1,1-diphosphonic acid) in untreated rats and in rats bearing intratibially transplanted osteosarcomas was investigated autoradiographically and scintigraphically. Also investigated was the effect of high doses of APD on survival time and tumor growth of osteosarcoma-bearing rats. Intravenous administration of APD resulted in high rates of APD accumulation in bones, tumor tissue and pulmonary metastases as well as in dose-related accumulation in the liver. No significant increase in the median survival time of tumor-bearing animals was achieved at the two dosage schemes tested, i.e. 2 X 23.5 mg/kg and 10 X 11.75 mg/kg APD. The growth of primary tumors was slightly increased by administration of APD. The chemosensitivity of the transplantable osteosarcoma model was demonstrated by comparison with dacarbazine-treated control animals.

Animals↗

PubMed1985

Early dynamic bone-imaging as an indicator of osseous blood flow and factors affecting the uptake of 99mTc hydroxymethylene diphosphonate in healing bone.

We determined the uptake of 99mTc-labeled hydroxymethylene diphosphonate in a surgically created defect in the canine tibia with early dynamic and delayed static bone scans. The defect consisted of a cortical bone window, ten by five millimeters, centered over the middle of the tibia. The dynamic bone scans consisted of sixty one-second images of the tibia, recorded immediately after the injections of 99mTc, and the static scans were single forty-five-minute uptake images of the tibia. These were performed and the dogs were killed at seven, fourteen, and twenty-eight days postoperatively. The dynamic scans detected the postoperative increase in tibial blood flow because the values calculated from these scans demonstrated a significant linear relationship to tibial blood flow determined with radioactive microspheres (r = 0.76, p less than 0.001). The increased uptake of 99mTc in the cortical defect that was detected with static scans was attributable not only to the increased blood flow but also to uptake by immature bone. Early dynamic bone-imaging increases the versatility of bone scintigraphy. The significant correlation between the dynamic scans and bone blood flow suggests that this non-invasive technique can provide a quantitative comparison of changes in regional blood flow in bone.

Animals↗

PubMed1979

[Bone scintigraphy with 99mTc-methylene diphosphonate in parodontopathy (author's transl)].

In a total of 20 patients (of these 8 without parodontopathy and 12 with parodontitis marginalis profunda), a quantitative scintigraphy of the jaw bones was carried out after application of 99mTc-methylene diphosphonate with a gamma camera computer system. In 8 patients without parodontopathies, approximately the same metabolic activity in the bone was found in the os occipitale as well as in the mandible and maxilla. The 12 patients with parodontitis marginalis profunda showed in contrast to this an appreciable raised bone metabolism in the region of the affected jaw bone. This finding was in agreement with corresponding alterations in the X-ray of the jaw. The use of bone scintigraphy in marginal parodontopathies thus provides in addition to the radiological finding information on processes of bone transformation and degradation which can be registered quantitatively. Digital analysis enables control of the course of therapie.

Adult↗

PubMed1979

Labeling efficiency and stomach concentration in methylene diphosphonate bone imaging.

When Tc-99m-labeled methylene diphosphonate was used 4.75 hr after reconstitution, stomach concentration was seen in the majority of patients. The number of patients with stomach concentration increases with time and is associated with the increasing amount of product breakdown. The reconstituted labeled MDP should not be used after 4-5 hr if stomach concentration is to be avoided.

Bone and Bones↗

PubMed1977

Implications of the 99mTc diphosphonate bone scan on treatment of primary breast cancer.

The 99mTc diphosphonate scan is important in the study of primary breast cancer. The short-term prognosis for scan-positive patients is poor. Serial bone scans provide a safe and reliable prognostic index in patients following mastectomy. By correlating the scan with biochemical tumor markers, a matrix of diagnostic tests may be developed that is capable of identifying high-risk patients who may benefit from systemic therapy.

Bone Neoplasms↗

PubMedDate not supplied

[Effect of methylene diphosphonic acid on certain processes in animal tissues].

It was shown that methylene diphosphonic acid, a structural analogue of pyrophosphate, exhibiting immunodepressant properties, in a dose of 40 micrograms/g body weight inhibits by 20% the activity of inorganic pyrophosphatase in the spleen of BALB mice and does not affect this enzyme in the liver or thymus. In noninbred albino mice inhibition of the activity of the enzyme was recorded only as a result of administering the preparation in a dose of 80 micrograms/g. Histological data on the kidneys, liver, lungs, spleen, lymphatic nodes and thymus indicate that the preparation does not exert a significant toxic action on the body.

Animals↗

PubMed1984

Iodine-131-labeled diphosphonates for the palliative treatment of bone metastases: I. Organ distribution and kinetics of I-131 BDP3 in rats.

I-131-labeled alpha-amino-(4-hydroxybenzylidene)-diphosphonate (BDP3) was examined in Sprague-Dawley rats for its bone affinity and other biokinetical characteristics. Iodine-131 BDP3 exhibited high bone affinity, with rapid blood clearance and renal excretion. Total-body retention measurements revealed an effective half-life of the activity of t1/2 = 169 hr. Similar kinetics were found in rat femurs, with t1/2 = 158 hr. Rats bearing osteosarcomas showed an enhanced uptake with a slower clearance (t1/2 = 177 hr). The amount of I-131 BDP3 excreted in urine agreed with the total body retention values. Fifty percent was excreted in the urine, as unchanged I-131 BDP3, by 24 hr after application. Almost no activity was found in the feces of the rats. LD50 measurements in rats amounted to 64 mg/kg. Because of these biokinetical characteristics and the simple labeling procedure, I-131 BDP3 is suggested as a radiopharmaceutical for the palliative treatment of pain that often accompanies disseminated bone metastases.

Animals↗

PubMed1983

Effect of hypophysectomy and hormonal replacement on the uptake of Tc-99m methylene diphosphonate in the metaphysis and shaft of the rat femur: concise communication.

We have investigated the uptake of Tc-99m methylene diphosphonate (Tc-MDP) in the metaphysis and shaft of the rat femur as affected by hypophysectomy and hormonal replacement with growth hormone and thyroxine. Two hours following injection of Tc-MDP, the metaphysis and a specimen of shaft were obtained and the metaphysis-to-shaft radioactivity ratio was measured. By five days after hypophysectomy the metaphysis-to-shaft ratio fell from a control value of 3.8 +/- 0.2 (mean +/- s.e.) to 2.4 +/- 0.2 (p less than 0.05) and remained significantly decreased throughout the 30-day study. When daily hormonal replacement with 0.5 mg of bovine growth hormone and 10 micrograms of thyroxine (both administered intraperitoneally) was given, beginning on the eighth day after hypophysectomy, the metaphysis-to-shaft ratio of Tc-MDP returned to control levels in twelve days. This model demonstrates the effect of growth hormone and thyroxine on the distribution of Tc-MDP, and may be useful as a radiobioassay of net circulating skeletal growth-promoting activity.

Animals↗

PubMedDate not supplied

Generalized skeletal response to 99mtechnetium methylene diphosphonate in rheumatoid arthritis.

The total body retention (TBR) and the 5- and 24-h lumbar spine to soft tissue (LS/ST) ratios of 99mtechnetium methylene diphosphonate was studied in 19 patients with rheumatoid arthritis (RA), 16 patients with metastatic tumors that did not involve the lumbar spine, 10 patients with chronic renal failure and 17 controls. The TBR was significantly higher in all groups compared to the controls. The 5-h LS/ST did not differ between any of the groups although the 24-h LS/ST ratios were significantly elevated in RA and those with chronic renal failure. The 24-h LS/ST in RA was correlated only with disease duration. The results are consistent with a generalized increase in bone turnover in RA and may explain the recognized lack of sensitivity of quantitative scintigraphic techniques in this disorder.

Adult↗

PubMed1982

Interference of dichloromethane diphosphonate with parathyroid hormone effects at the bone but not at the kidney level.

Treatment with dichloromethane diphosphonate (Cl2MDP, 10 mg P/kg s.c. for 3 days) did not abolish the rapid hypocalciuric effect of acute administration of parathyroid hormone (PTH) to thyroparathyroidectomized (TPTX) rats. Cl2MDP impaired, however, the slower hypercalcemic response to PTH. This latter effect of Cl2MDP did not result from increased renal excretion of calcium. Thus, Cl2MDP does not interfere with the kidney but with the bone effect of PTH. This finding explains, at least in part, why, under treatment with Cl2MDP, there is still an effective regulation of plasma calcium.

Animals↗

PubMed1983

[Whole-body retention of 99mTc-methylene diphosphonate in skeletal diseases].

The 24 h-whole-body retention (WBR), determined by a whole-body counter, may be used to quantify exactly bone seeking properties of a radiopharmaceutical. The 24h-WBR of 99mTc-methylene-diphosphonate was determined in 200 patients and was found to be independent of kidney function if this function was normal or only slightly diminished. The 24h-WBR was slightly dependent on age since it decreased up to 20 years of age, reaching a minimum at 20-25 years, and then increased with increasing age. Normal values of 24h-WBR for individuals of more than 20 years of age were 31.8 +/- 5% of injected dose. Not more than two focal accumulations, i.e. skeletal metastases, failed to elevate the 24h-WBR significantly (p less than 0.1). However, a highly significant (p less than 0.001) difference to normals was found in patients with multiple metastases (24h-WBR: 38.2 +/- 7%), with diffuse osseous involvement as in primary hyperparathyroidism (24h-WBR: 49 +/- 11.7%, p less than 0.001) or with osteoporosis (24h-WBR: 45%). The 24h-WBR was found to be very sensitive in grading diffuse osseous involvement. This was shown in single-tumor patients by follow-up as the 24h-WBR in addition to bone scans was useful to describe progression or remission. Moreover, the 24h-WBR correlated closely with results of bone marrow biopsies in a small group of patients with malignancies of the lymphoreticular system.

Adolescent↗

PubMed1983

Effect of dichloromethylene diphosphonate on bone metabolism in calcium and phosphorus-depleted rats.

In this paper we examine the effects of dichloromethylene diphosphonic acid (Cl2MDP) (1.0 mg P/kg) in rats which have high levels of bone resorption due to the consumption of low-calcium (0.2%) or low-phosphorus (0.2%) diets. Cl2MDP increased the number of osteoclasts as shown by an increased length of resorbing surface but decreased osteoclast activity as measured by the linear rate of bone resorption. These effects appeared to be greater in the low-calcium and low-phosphorus rats, where resorption rates were higher than normal. However, these interactions between dietary and Cl2MDP effects were not statistically significant by analysis of variance. Endosteal bone formation was decreased by Cl2MDP, and the magnitude of this was significantly less in rats receiving low-calcium or low-phosphorus diets where endosteal bone formation was already low. Small but statistically significant decreases were also evident in periosteal bone formation and mineralization parameters in Cl2MDP-treated rats whether on normal or low-calcium or low-phosphorus diets.

Animals↗

PubMed1983

[Biokinetics of osteotropic radiopharmaceuticals in metabolic osteopathy--comparison of 47Ca and 99mTc-methylene-diphosphonate (MDP)].

Plasma clearance and osseous accumulation rates of 99mTc methylene diphosphonate (MDP) in the lumbar spine were measured in 11 patients with osteoporosis (OP), 7 patients with hyperparathyroidism (HPT), 4 patients with osteomalacia (OM) and in 3 patients (N) who were studied to exclude metabolic bone disease. The findings in 19 patients were compared with the results of 47Ca kinetics. The plasma elimination of 99mTc-MDP during the first hour after application was normal in almost all the patients. The 99mTc-MDP accumulation rates in the lumbar spine were raised in patients with HPT and OM (p less than or equal to 0.01) and normal in patients with OP and N (p greater than 0.05). 47Ca kinetics were disturbed in most of the patients with metabolic bone disease, with minimal deviations in OP. The comparison of 99mTc-MDP accumulation rates with the results of 47Ca kinetics revealed significant correlations with exchangeable bone and soft tissue calcium. The correlations with total calcium turnover and calcium accretion were poor. Only half of the patients had equal results of 99mTc-MDP accumulation rates and bone calcium accretion rates. It is concluded that the 99mTc-MDP uptake by bone is an index of bone metabolism presumably of the organic matrix, whereas 47Ca kinetics represent the mineral metabolism of bone.

Adult↗