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99mTc-methylene diphosphonate (MDP) bone scintigraphy demonstrated localization in an intracranial metastasis of osteogenic sarcoma. This unusual case suggests that bone scintigraphy may have diagnostic value in the early diagnosis of metastatic ossifying lesions.
Whole body retention (WBR) and urinary excretion (UE) of 99mTc-diphosphonate were determined in 161 healthy adults and the results were compared to accepted biochemical markers of bone turnover. WBR was corrected for total body bone mineral (TBBM) and UE for forearm bone mineral content (BMC). Both uncorrected and corrected retention measurements were highly significantly correlated to the biochemical markers (P less than 0.001), but the r values were low (0.22-0.64). All bone turnover variables demonstrated considerably higher levels of bone turnover in postmenopausal women than in premenopausal women (P less than 0.001), whereas the variables were unchanged with age in men. The correction of WBR for TBBM and UE for BMC increased the validity of the retention methods and the two calculations gave exactly the same results on a group basis, both demonstrating significantly higher bone turnover in women than in men in each age group (P less than 0.05-P less than 0.001). All the turnover variables were measured in a group of perimenopausal women (n = 33). The data clearly demonstrated that bone turnover is menopause dependent, whereas age in itself is of minor significance.
A positive 99mTc-methylene diphosphonate bone scan was obtained in a case of pelvic osteomyelitis in a 15-year-old girl. An 111In-labelled leucocyte scan confirmed the presence of pus, gave a more accurate anatomical location than was obtained by the bone scan, and enabled the most suitable surgical route to be selected.
The distribution of 99mTc-labelled ethylene 1-hydroxy-1,1-diphosphonate (EHDP) in young rats was studied 1, 3, 6 and 9 h after intraperitoneal injection. The concentration of 99mTc in bone was 8-10 times higher than that in the kidneys and 20-1000 times higher than those in other soft tissues. The concentration in bone remained constant throughout the observation time. In some of the animals sacrificed after 3, 6, or 9 h the uptake in the liver and spleen was higher than that found in the majority of the animals.
The kinetics of 99mTc-methylene diphosphonate (MDP) and 47Ca were studied in three patients with osteoporosis, three patients with hyperparathyroidism, and two patients with osteomalacia. The activities of 99mTc-MDP were recorded in the lumbar spine, paravertebral soft tissues, and in venous blood samples for 1 h after injection. The results were submitted to deconvolution analysis to determine regional bone accumulation rates. 47Ca kinetics were analysed by a linear two-compartment model quantitating short-term mineral exchange, exchangeable bone calcium, and calcium accretion. The 99mTc-MDP accumulation rates were small in osteoporosis, greater in hyperparathyroidism, and greatest in osteomalacia. No correlations were obtained between 99mTc-MDP bone accumulation rates and the results of 47Ca kinetics. However, there was a significant relationship between the level of serum alkaline phosphatase and bone accumulation rates (R = 0.71, P less than 0.025). As a result deconvolution analysis of regional 99mTc-MDP kinetics in dynamic bone scans might be useful to quantitate osseous tracer accumulation in metabolic bone disease. The lack of correlation between the results of 99mTc-MDP kinetics and 47Ca kinetics might suggest a preferential binding of 99mTc-MDP to the organic matrix of the bone, as has been suggested by other authors on the basis of experimental and clinical investigations.
Accumulation of 99mTc-diphosphonate was observed in 2 of 12 patients with liver metastases who had primary adenocarcinoma of the large bowel. The area of excessive radionuclide concentration corresponded well to the location of the hepatic metastases. The literature on this subject is reviewed and a possible mechanism of radionuclide accumulation is discussed.
Accumulation of 99mTc-methylene diphosphonate was observed in liver metastasis resulting from stomach carcinoma. This accumulation was located around the lesion on an emission-computed tomogram. This has not been previously reported.
This communication reports a presumed increased localization of 99mTc-diphosphonate in a surgical scar 5 months post-op at the site of a medium sternotomy incision. The possible mechanisms for this observation are commented on and a brief review of the observed sites of soft-tissue uptake of 99mTc-labeled bone imaging agents is given.
In two patients with metastatic disease more lesions were detected on scintigraphs obtained with the 'low uptake' bone-scanning agent dimethyl-amino-diphosphonate. The results in these two patients provide practical support for the suggestion that bone-scanning agents with low uptake in normal bone, but high tumour-to-normal bone ratios, will allow better delineation of focal bone abnormalities.
It has been reported that bioactive glass-ceramics containing crystalline oxy- and fluoroapatite [Ca10(PO4)6(O,F2) and wollastonite (CaSiO3), chemical composition: MgO 4.6, CaO 44.9, SiO2 34.2, P2O5 16.3, CaF2 0.5 in weight ratio] bond to bone tissue through the formation of an apatite (a calcium and phosphorus-rich layer) on the ceramic surface. In this study, the influence of disodium (1-hydroxythylidene) diphosphonate (DHTD) on the bonding between bone and glass-ceramics containing apatite and wollastonite was investigated. Rectangular ceramic plates (15 mm x 10 mm x 2 mm, abraded with #2000 alumina powder) were implanted into the tibial bone of mature male rabbits. DHTD was administered daily by subcutaneous injection to groups 1-5: group 1-4 at doses of 20, 5.0, 1.0, and 0.1 mg/kg body wt/day for 8 weeks; and group 5 at a dose of 5 mg/kg body wt/day for 4 weeks. Group 6 was given injections of saline as a control. At 8 weeks after implantation, the rabbits were killed. The tibiae containing the ceramics were dissected out and used for a detachment test. The failure load, when an implant became detached from the bone, or when the bone itself broke, was measured. The failure loads for groups 1-6 were 0 kg, 0 kg, 8.08 +/- 2.43 kg, 7.28 +/- 2.07 kg, 5.56 +/- 1.63 kg, and 6.38 +/- 1.30 kg, respectively. Ceramic bonding to bone tissue was inhibited by a higher dose of DHTD (groups 1 and 2).(ABSTRACT TRUNCATED AT 250 WORDS)
Rats received a single intravenous injection with liposome-encapsulated dichloromethylene diphosphonate (C12MDP). This treatment resulted in the elimination of macrophages in spleen and liver within 2 days. Macrophages ingest the liposomes and are destroyed by the drug, which is released from the liposomes after disruption of the phospholipid bilayers under the influence of lysosomal phospholipases. Repopulation of macrophages in spleen and liver was studied at different time intervals after treatment. Macrophages in the liver (Kupffer cells) and red pulp macrophages in the spleen were the first cells to reappear, followed by marginal metallophilic macrophages and marginal-zone macrophages in the spleen. Different markers of the same cell did not reappear simultaneously. On the other hand, the same marker (recognized by the monoclonal antibody ED2) reappeared much more rapidly in the liver than in the spleen. The present results in the rat were different from those earlier obtained in the mouse. Red pulp macrophages were the first cells and marginal zone macrophages were the last cells to repopulate the spleen in both rodents after treatment with C12MDP liposomes. However, there was much more overlap in the repopulation kinetics of splenic macrophage subpopulations in the rat, when compared with the mouse.
The localization of 99mTc-methylene diphosphonate (99mTc-MDP) in mouse osteosarcoma was studied using a skeletal scintigraphic method and macro- and microautoradiographic methods. On the skeletal scintigraph, the tumor showed a high uptake of 99mTc-MDP and its concentration was about 20 times as high as the value seen in the muscular tissue. The macroautoradiography showed high activity in the tumor bone region and little activity in the nonossified region. On the microautoradiography, the activity of 99mTc-MDP was localized in the mineralized matrix of tumor bone and was almost nil in the nonmineralized matrix (osteoid) and the tumor cells. These findings indicate that the mineralization of the tumor bone matrix plays an important role in 99mTc-MDP uptake in osteosarcoma.
Dichloromethylene diphosphonate (Cl2MDP) was given at doses of 4 mg/kg and 10 mg/kg daily for 7 days to adult thyroparathyroidectomized rats fed a low calcium diet. Primary metaphyseal trabeculae in Cl2MDP-treated rats were more numerous and longer than in controls. The light and electron microscopic appearance of osteoblasts, osteocytes and osteoclasts were unaltered by Cl2MDP. Bone alkaline phosphatase was significantly elevated in rats given Cl2MDP but adenosine triphosphatase activity was unchanged. Bone fat-free weight, fat-free minus ash weight, and bone calcium and phosphorus concentration were reduced significantly in rats given 10 mg/kg Cl2MDP compared to controls. Bone magnesium concentration was significantly elevated in rats given 10 mg/kg Cl2MDP. Serum calcium and phosphorus concentration were lower in Cl2MDP-treated rats. These results suggest that Cl2MDP is capable of altering bone remodeling, enzyme activity and mineral content, without significantly altering bone cell morphology, independent of the effects of parathyroid hormone, calcitonin, and dietary calcium.
The bone scan may be of value in the assessment of patients with metabolic bone disease. However the superiority of the bone scan when compared to radiology in conditions such as renal osteodystrophy, osteomalacia, primary hyperparathyroidism, and osteoporosis requires substantiation with the newer radiopharmaceuticals which have a higher affinity for bone. Two methods of quantitating skeletal uptake of tracer have been assessed to try to remove the subjective aspect of bone scan evaluation. Measurements of bone to soft tissue ratios have proved clinically disappointing, but 24 hour whole body retention of diphosphonate appears to provide a sensitive index of increased bone turnover.
The influences of dilution, storage and pH on the distribution of 99m-technetium methylene diphosphonate (99m-Tc-MDP) in bone and various soft tissues have been investigated in the rat. The results show a marked departure from normality when large dilution factors and very acidic or basic preparations are used.
A case of primary neuroblastoma in a seven year old boy is presented in which 99Tcm methylene diphosphonic acid (MDP) used as a bone scanning agent localised in the primary tumour. The possible mechanism for this is discussed.
Sham-operated (SO) and paraplegic rats were treated from the day of operation during a period of 4 or 6 weeks with salmon calcitonin 4 IU/kg/day or a diphosphonate (APD) 1mM/kg/day or indomethacin 2.5 mg/kg/day. The consequence of spinal cord section on the femur and tibia is a loss of mineral which affects predominantly trabecular bone (-24 and -13% in calcium content for the tibial metaphysis and the whole bone, respectively, when compared with the SO controls), a twofold increase in bone blood flow as measured by the technique of the microspheres trapping, a moderate decrease of the 72 hour 45Ca accretion rate in the bone shaft, and an increase in the number of metaphyseal osteoclasts in the tibia. In paraplegics, all three drugs inhibit bone loss to some degree, calcitonin and indomethacin being mostly effective on the cortical bone of the shaft, and APD tremendously increasing the trabecular network of the metaphysis. APD is the only drug to exhibit a significant effect on the calcium content of the bones of the SO controls, but some effect is apparent for calcitonin on X-rays and histological preparations. The increase in bone blood flow in paraplegics is unaffected, this point being discussed in view of the hypothesis of the resorptive action of prostaglandins produced by newly formed vessels. 45Ca accretion rate increases in the shaft of calcitonin-treated paraplegics, whereas it decreases in APD-treated controls and paraplegics. The number of osteoclasts decreases in paraplegics treated with calcitonin and indomethacin, and increases in both controls and paraplegics treated with APD.(ABSTRACT TRUNCATED AT 250 WORDS)
An implanted biomaterial can be transformed into young bone after some months, but it has not necessary reached full biofunctionality. Mineral concentration kinetics and crystal-structure studies, still being carried out in our group, are completed here by biofunctionality determinations. A natural coral is implanted in vivo at the cortical level of the femoral diaphyoff++ in rabbits. Diphosphonates molecules labeled with radioactive 99mTc are then injected in rabbits and the fixation of the radioactivity is analyzed in several sites for 8 mo after the implantation. Nuclear instruments and methods are used for the measurements. Four successive cycles of osseous remodeling are determined before reaching a biofunctional phase.