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Strontium-89 chloride (Metastron) for palliative treatment of bony metastases. The University of Minnesota experience.

Strontium-89 chloride (Metastron) is an FDA-approved treatment for palliation of cancer pain. We evaluated blood count changes and pain relief in 28 patients with widespread painful bony metastasis treated with strontium-89 at the University of Minnesota Hospital and Clinics. Eighteen patients had prostate cancer (all hormone-refractory cancer), seven patients had breast cancer, and three patients had lung cancer, all previously treated with either radiation, chemotherapy, or a combination of the two. Serial blood counts were performed weekly up to 8 weeks and at 12 weeks after administering Metastron. Pain scale and blood values were monitored simultaneously. The mean baselines of hemoglobin (Hgb), white blood count (WBC), and platelets (Plts) were 11.4, 5900, and 258,000, respectively. The mean dose of Metastron was 3 mCi (range 2.2-4.4). The median time (range) to nadir was about 6 weeks. The percentage reductions relative to baseline were 32% (range 0-72%) for WBC; 14% (range 0-50%) for Hgb; 15% (range 0-47%) for the red blood cell (RBC) count; and 40% (range 0-85%)for Plts. We did not find a close relationship among the baseline blood count, reduction of subsequent blood counts, or previously irradiated active bone marrow volume. The median time of survival was 23 weeks (range 2-66 weeks). At 12 weeks, 29% of patients had moderate to dramatic improvement of pain, 32% had some relief of pain, and 50% had no improvement in pain. Thirty-two percent of the treated patients required additional palliative external beam radiation to their bony lesions within the study period. Our results show that Metastron for palliation for bony metastases should be used with caution because of moderate to severe bone marrow toxicity, especially in platelets, associated with its use. Careful evaluation of patients given Metastron is needed to assess accurately its full benefit.

Adult↗

Strontium mobility in germinating seeds and plants.

The uptake of strontium in the bean plant (Phaseolus vulgaris) was linear for the first 34 hr during continuous exposure to radiostrontium. After 35 hr there was a sharp increase in the rate of uptake to 48 hr. Radioactivity could be detected in the plant as early as 1 hr after addition of radiostrontium to the growth medium.Seventy-five percent of the radiostrontium was located in the seed coat immediately after soaking bean seed in an (89)Sr solution. This radioactivity in the seed coat decreased rapidly up to the tenth day, while the proportion of strontium in the cotyledons increased, after which time the proportion of radiostrontium in the cotyledons began to decrease. The amount of radioactivity of the seedling axis increased constantly, as did the activity of the first and second leaves after their appearance on about the seventh day. The radioactivity in the developing third and fourth leaves of cotton plants (Gossypium hirsutum) increased at the expense of the radioactivity in the first 2 leaves and stems. This represents a movement into certain parts and then a retranslocation out of these parts as other tissue begins to develop.

Plant Development↗

Distribution of strontium-90 in a 1959 wheat sample.

At least 22 percent of the strontium-90 found in a sample of wheat harvested in 1959 was due to direct deposition. Twenty-seven percent of the total strontium-90 content of this wheat sample was contained in the outermost bran layer.

Food↗

Strontium-90 in Alaska.

Strontium-90 concentrations have been determined in a variety of foods used by the native population. Caribou from the tundra carry 10 to 20 times the level of domestic cattle. Eskimos for whom caribou is a staple in the diet are found to have four times the strontium-90 content of the average for the world population of the North Temperate Zone.

Alaska↗

Strontium-89 chloride in the treatment of bone metastases from breast cancer.

Sixty-four patients with painful metastatic breast cancer in bone were treated with 2 MBq/kg of strontium-89 chloride as a single intravenous injection. Patients were followed with records of medication, hematology parameters, serial bone and Sr-89 bremsstrahlung images and with a point pain score scale (10-0). The response was assessed during a 6-month period of follow-up. Fifty-two of 64 patients (81%) showed at least a moderate improvement. Eighteen out of the 52 responders showed a dramatic decrease in bone pain (35%), 21 (40%) presented a satisfactory response and in 13 cases (25%) the response was moderate. Only 12 patients (19%) from the whole group did not feel any improvement on pain palliation. A statistically significant decrease of pretreatment levels of platelets and leukocyte counts was observed after 4-6 weeks of therapy in 50 (70%) patients. Although most patients showed no change in their bone scans after 3 months of treatment, an obvious improvement was observed in 3 of them. Furthermore no additional painful metastases on their bone scintigraphic images were observed. The selective strontium-89 local uptake in metastatic sites was also confirmed directly by bremsstrahlung scans which were absolutely comparable to the respective 99mTc bone scans. Precautions have been taken against Sr-89 contamination from the patients' blood or excretions.

Bone Neoplasms↗

Strontium-89 therapy for the pain of osseous metastases.

A Phase I and II study has been conducted of the safety and efficacy of 89Sr (injected i.v. as the chloride) to alleviate bone pain due to osseous metastatic disease. Potential attendant hematologic toxicity was also examined. Strontium-90 impurities were always less than 1.5%, employing a new quality control technique which detects the 90Y "daughter". Thirty-eight patients with pain due to osseous metastases requiring regular narcotic more than twice a day, documented by an abnormal bone scan and radiography, received 45 doses (1-4.5 mCi, 16-70 microCi/kg) of 89Sr after informed consent. The performance status (Karnofsky scale) ranged from 20-80%. One patient had complete pain relief while 22 other doses yielded at least a 25% reduction in narcotic requirement lasting at least 1 mo and/or 20% improvement in Karnofsky scale rating. Two patients had marked to complete relief in tumor sites which were not fractured, with no change in fracture pain. Twenty-two did not respond. Response was independent of narcotic requirements, tumor type, or Karnofsky status. No hematologic toxicity occurred. Strontium-89 may be useful as adjuvant therapy for diffuse bone pain, but a double-blind study comparing it to other nonnarcotic modalities is required.

Bone Neoplasms↗

Studies on inhibition of intestinal absorption of radioactive strontium. IX. Relationship between biological activity and electron microscopic appearance of alginic acid components.

The inhibitory action of alginate on intestinal absorption of radioactive strontium was investigated in order to correlate the biological activity with the chemical composition. Alginate from Laminaria hyperborea was partially hydrolyzed with oxalic acid and the degradation products were fractionated into polymannuronic and polyguluronic acid. The activity of these products was assessed biologically in rats and morphologically by electron microscopy. Sodium polymannuronate was found to be less effective than sodium polyguluronate in preventing absorption of radiostrontium. The inhibition of absorption of radio-calcium was low and not affected by hydrolysis or fractionation. When dried from dilute aqueous solutions, the polymannuronate retained the original helical structure of alginate, while the polyguluronate showed a strong tendency to coagulate, forming granules. The variation in the biological activity was attributed to the morphological differences between these alginic acid components and it is suggested that the degree of uncoiling of the polyguluronate chain in water is greater than that of the polymannuronate chain, thus making the carboxylate ions more accessible to strontium.

Alginates↗

Content of strontium, lithium and calcium in selected milk products and in some marine smoked fish.

The strontium, lithium and calcium contents have been determined in 87 samples of five kinds of milk-fermented products, as well as in 93 samples of ten kinds of marine smoked fish. The samples were purchased on the local market. The representative samples were dry ashed in quartz crucibles and the ash was treated with suitable amounts of conc. HCl and a few drops of conc. HNO3. The obtained sample solution was then used for the determination of Sr, Li and Ca by the flame atomic absorption spectrometry (AAS) method. Ca and Li were determined using the air-acetylene flame and Sr with nitrous oxide-acetylene flame, according to the manufacturer's recommendations. The contents of Sr in the fermented milk products ranged from 0.21 to 0.79 (mean 0.44 +/- 0.07) and in the marine smoked fish from 0.02 to 4.63 (mean 1.16 +/- 0.24) mg/kg of the edible form of both products. Li contents in the milk products ranged from 0.01 to 0.50 (mean 0.07 +/- 0.04) and in the smoked fish from 0.00 to 0.58 (mean 0.11 +/- 0.08) mg/kg. The calcium was highest in the milk products and ranged from 1,010 to 2,020.0 (mean 1,377 +/- 143) mg/kg. In the smoked fish calcium varied strongly and ranged from 40 to 1,052 (mean 303 +/- 53) mg/kg of the edible form. The calculated average ratio of strontium to calcium (mg Sr/1 g Ca) in the milk beverages and yogurts amounted 0.32 and in the smoked fish was 12 times as high and amounted 3.84. The main purpose of this work was to present Ca, Sr and Li together. This is justified because Sr and to some extent also Li are able to modulate Ca metabolism and vice versa.

Animals↗

Strontium and diet at Hayonim Cave.

Faunal and human bones from the Natufian and Aurignacian levels of Hayonim Cave, Israel, were analyzed for calcium, strontium, and phosphate, in order to investigate the efficacy of strontium measurements for determining the proportion of meat in human diets. This site in the western Galilee was appropriate for a test of the technique since a) herbivore and carnivore fauna were present in numbers from two different time periods, b) well-characterized human skeletons were also present in at least one of these levels, and c) the diets of the individuals examined were basically well understood. On the basis of Sr/Ca values, a large difference was observed between Natufian herbivore bones and carnivore bones in the manner predicted by the diets of these species. Sr/Ca values for the adult humans from the same level fell midway between the herbivore and carnivore ranges. However, a different pattern was observed for Aurignacian fauna; no difference could be found between Sr/Ca ratios of herbivore and carnivore bones. The findings suggest that, in certain circumstances, the technique may provide important new paleodietary information. However, at any given site or level, both herbivore and carnivore fauna should be analyzed before conclusions about human diets are drawn from it.

Animals↗

Time-dependent excretion of lithium, sodium, potassium, rubidium, magnesium and strontium in the urine of a multiple sclerosis patient.

Field desorption mass spectrometry and stable isotope dilution have been used for direct trace analysis of metals in urine. Samples were collected over 24 h at 2 h intervals from a hospitalized multiple sclerosis patient. Quantitative determinations of Li+, Rb+, Mg2+ and Sr2+ from individual samples have been made and correlated with the amounts of urine excreted as well as with the time of day. The concentrations of Na+ and K+ were determined by flame photometry. The quantities of metals excreted in urine during the course of 24 h were 0.0129 mg for lithium, 4700 mg for sodium, 2100 mg for potassium, 1.4 mg for rubidium, 78.8 mg for magnesium and 0.2356 mg for strontium. The maximal absolute quantities excreted of all metals determined correspond with the largest volume of urine. The highest amounts of potassium, rubidium and strontium were found in urine during the daytime (8.00-20.00), whilst magnesium was excreted increasingly during the night hours (20.00-8.00). The excretion of lithium and sodium is fairly even over the entire 24 h period. It is noteworthy that similarities in the excretion profile and the concentration course are observed between Li+ and Na+ on one hand and between K+ and Rb+ on the other. Moreover, the lower concentration of Rb+ ions in urine of multiple sclerosis patients, in comparison to healthy individuals and clinical controls as reported previously, was confirmed.

Adult↗

Interatomic potential models for natural apatite crystals: incorporating strontium and the lanthanides.

A comprehensive set of interatomic potential parameters for modeling natural apatite crystals is presented. These potentials build on those previously used in research on apatites with new potentials fitted empirically to crystal structures and their properties using the GULP program. We demonstrate that the new potentials produce good models for the different compounds used for fitting, as well as for several natural apatites. Also presented are predicted enthalpies of mixing of strontium and calcium apatites and predicted cation site preferences in strontium calcium fluorapatite.

Apatites↗

Integrated management of radioactive strontium contamination in aqueous stream systems.

A combination of biomass treatment, fluidized bed/membrane reactor, and a minimum-suspension fluidized bed reactor is proposed to remove strontium cations from aqueous solutions, such as those generated by nuclear reactors. After conducting a series of screening tests, three adsorbents were selected for their suitability and high adsorptive capacity. The proposed combination uses Chlorella vulgaris in a packed column, followed by the fluidized bed/membrane reactor with bentonite powder in suspension. The membrane is primarily used to retain bentonite powder in the reactor. However, the same can be designed to remove additional amount of contaminant from the aqueous stream. The final separation is carried out in a fluidized bed containing resins that are suspended with minimal airflow. In laboratory scale, a flow rate of 600 ml/h was achieved for 30 min during which period the inlet concentration of 100 mg/l was reduced to 2.5 mg/l at the outlet. Bio-encapsulation with thermophilic bacteria and subsequent separation is proposed at this point in order to reduce the concentration to an even lower level. The proposed separation scheme offers an acceptable solution to removing strontium while minimizing the generation of secondary waste.

Adsorption↗

The effect of lactose and iron on strontium absorption.

In rats fed on a milk diet with or without the addition of lactose and/or iron the transileal strontium-85 transfer was higher by 14-38% and the intestinal strontium retention lower by 6-23% than in control rats fed on standard laboratory food.

Animals↗

Effect of 1,25-dihydroxycholecalciferol on sarcoplasmic reticulum calcium transport in strontium-fed chicks.

Feeding of chicks with strontium, an inhibitor of 1,25-dihydroxycholecalciferol synthesis in kidney, during 7 days, significantly depressed the initial rate of calcium uptake and calcium storing capacity of sarcoplasmic reticulum membranes from skeletal muscle. Oral administration of 1,25(OH)2D3 to strontium-fed animals returned calcium transport values to normal. The changes observed could not be related to differences in the relative proportions of transport ATPase and calcium binding proteins. The results are consistent with a role of 1,25(OH)2D3 in muscle function.

Animals↗

Lattice parameters and cation distribution of solid solutions of calcium and strontium hydroxyapatite.

Solid solutions of strontium and calcium hydroxyapatite were synthesized by solid-state reaction. Lattice parameters of these compounds were determined using two types of Guinier cameras. They vary linearly with the molar percentage of strontium hydroxyapatite. The distribution of Ca and Sr ions over the fourfold and sixfold positions in the apatite structure was determined by comparing experimental and calculated values for the intensity ratios of suitable reflections. A slight, although significant, preference of Sr for the sixfold position was found. An ideal behavior is predicted for these solid solutions.

Calcium↗

The assessment of intestinal calcium absorption using stable strontium.

The availability of currently used methods of measuring intestinal calcium absorption is limited by their expense and complexity. Since this measurement may be important in selecting appropriate therapies for patients with osteoporosis, a simpler procedure is required. This paper describes a test which measures the intestinal absorption of stable strontium. A comparison of this test with the single-isotope radio-calcium absorption test in the same group of patients showed a close correlation between the fractional absorption rates of the two elements (r = 0.93, P less than 0.001). Subjects were correctly categorized as having normal or low absorption in 12 out of 13 cases (92%) and the value in the misclassified subject was at the borderline between normal and low calcium absorption. The convenience, low cost, and freedom from radioactivity of stable strontium make it suitable for routine clinical use and, if necessary, repeated testing. If these early results are confirmed, this test will make the assessment of calcium absorption much more widely available.

Aged↗

Strontium supports synaptic transmission and long-lasting potentiation in the hippocampus.

(1) Synaptic transmission was studied in isolated transverse hippocampal slices from guinea pigs. Extracellular evoked potentials were recorded in the region CA1. (2) Changing the normal perfusion solution (containing 2 mM Ca2+) to calcium-free Ringer abolished synaptic transmission which was again restored by adding strontium. A synaptic efficacy of 25--50% ofn normal was obtained for 10 mM Sr2+. (3) Two different synaptic inputs to CA1 pyramidal cells were tested with respect to their ability to produce long-lasting synaptic potentiation after tetanization in strontium Ringer. Following a brief tetanus the field EPSP and, especially, the population spike were greatly enhanced. (4) The potentiation so produced was similar to the long-lasting potentiation seen in the normal slice, because it (i) had a very long duration (hours), (ii) was specific for the tetanized pathway, (iii) showed potentiation of both 'volley-EPSP' and 'EPSP-spike' relations, and (iv) was accompanied by short-lasting (less than 5 min) generalized depression.

Animals↗

Uptake and retention of strontium, iodine and caesium in lowland pasture following continuous or short-term deposition.

Data from the extensive routine environmental monitoring programme around the nuclear reprocessing plant at Sellafield, West Cumbria, are analysed for soil to plant uptake of strontium, iodine and caesium. Relative to the top 10 cm of soil, dry weight concentration ratios derived for lowland pastures for strontium, caesium and iodine are 9, 3 and 2 respectively. Long-term trends indicate a 'spring flush' of activity in vegetation, although this is not statistically significant. Uptake of caesium and iodine is highest generally for mosses and lichen and lowest for grass. The vegetational field loss of these elements over the first 50 days following deposition, is described by: Sr: Reff(t) = 0.7e-0.15t + 0.25e-0.049t + 0.05e-0.011t I: Reff(t) = 0.7e-1.26t + 0.25e-0.17t + 0.05e-0.092t Cs: Reff(t) = 0.6e-0.87t + 0.2e-0.20t + 0.16e-0.065t + 0.04e-0.011t where t is in days. The functions are consistent with the effects of washoff and grazing. Equilibrium plant:soil concentration ratios are established for caesium within about 8 months following short-term deposition. Soil distribution profiles for caesium imply a half-time for transfer through the surface layers of about 6 years.

Cesium Radioisotopes↗