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Mechanism of uptake of strontium isotopes in aspergillus lesions.

Observations on experimental aspergillosis of chorioallantoic membranes confirmed that strontium-85 uptake in aspergillus lesions was directly due to infection by the fungus. Such uptake was not found in normal or in Toxoplasma gondii-infected control membranes. Further, the avidity of radionuclide uptake was proportional to the mycelial mass, as previously observed clinically. Investigations on 85Sr containing malt extract broth Aspergillus fumigatus cultures revealed that fungal hyphas did not contain the major proportion of radioactivity, but culture filtrates did, and suggested that a fungal metabolite may be responsible for radiostrontium binding. Subsequent radiochromatography of filtrates obtained from A. fumigatus cultures confirmed the existence of such a metabolite. Several clinical and laboratory observations support the concept that an aspergillus metabolite at foci of infection binds 85Sr and 87mSr.

Aspergillosis

Palliation of bone metastases in prostate cancer. Hemibody irradiation or strontium-89?

The palliation of bone pain is a common clinical problem once metastatic prostate cancer has escaped from hormonal control. This retrospective study compares the results of treatment using hemibody irradiation (HBI) at the Royal Marsden Hospital (27 cases) with isotope therapy using the bone-seeking isotope strontium-89 (89Sr) at Southampton General Hospital (51 cases). Prior to analysis patients were matched for potential prognostic factors (performance status, bone scan extent of disease, age, histology and duration of hormone response) to minimize the effect of treatment selection bias. Pain control assessed at 3 months was similar for HBI and matched 89Sr cases, with 63% and 52% respectively showing some benefit. Median survival was similar for these groups at 20 and 21 weeks respectively. The unmatched 89Sr group, which had more favourable prognostic factors, had a better outcome with 96% showing improvement in pain and with a median survival of 59 weeks. Subsequent univariate analysis demonstrated that performance status and extent of disease on bone scan were of overriding importance in determining outcome. Transfusion requirements were higher for the HBI group than for the matched 89Sr group (50% and 25% respectively) but other bone marrow toxicity was similar. Despite routine anti-emetic therapy 37% of patients treated with HBI had some nausea or vomiting. Although expensive, 89Sr appears as effective a treatment option as HBI. Response is most likely with either approach when patients have a good performance status and a limited extent of disease.

Actuarial Analysis

Bone scanning: principles, technique and interpretation.

Bone scanning is most useful in the detection of bone metastases. The recent introduction of new radiopharmaceuticals and instrumentation has reduced the time needed to perform the study and its relative cost, while increasing the usefulness of the study in detecting roentgenographically occult diseases. Metastatic disease is used as the pathophysiologic model for understanding the principles of bone scanning. When a tumor invades bone, in addition to causing bone destruction, it also causes reactive bone formation or repair. It is here that radioisotopes are of considerable value, since some radionuclides are incorporated into the hydroxyapatite crystals of reactive bone. Bone repair is described as occurring in three phases. In Phase I, the roentgenogram shows no change in bone density, but the scan is abnormal. In Phase II, both scintigraphic and roentgenographic abnormalities increase, and in Phase III, when the osteoid has calcified completely, the roentgenogram shows radiodensities and the scan appears almost normal. Fewer than 5 per cent of patients have a normal scan in the presence of an abnormal roentgenogram. Presently, most bone scans are performed with phosphate compounds labeled with -99m-Tc. In the past, 85-Sr, 87M-Sr, and 18-F were more broadly used. Scanning may be performed on either a rectilinear scanner or a scintophoto (gamma) camera. Areas which are abnormal on bone scan should be interpreted with current roentgenograms in the light of clinical findings.

Autopsy

Bone scintiscanning updated.

Use of modern materials and methods has given bone scintiscanning a larger role in clinical medicine, The safety and ready availability of newer agents have led to its greater use in investigating both benign and malignant disease of bone and joint. Present evidence suggests that abnormal accumulation of 99mTc-polyphosphate and its analogues results from ionic deposition at crystal surfaces in immature bone, this process being facilitated by an increase in bone vascularity. There is, also, a component of matrix localization. These factors are in keeping with the concept that abnormal scintiscan sites represent areas of increased osteoblastic activity, although this may be an oversimplification. Increasing evidence shows that the bone scintiscan is more sensitive than conventional radiography in detecting focal disease of bone, and its ability to reflect the immediate status of bone further complements radiographic findings. The main limitation of this method relates to nonspecificity of the results obtained.

Bone Diseases

Bone scanning.

Scanning is based on the uptake of a nuclide by the crystal lattice of bone and is related to bone blood flow. Cancer cells do not take up the tracer. Normally, the scan visualizes the highly vascular bones. Scans are useful and are indicated in metastatic bone disease, primary bone tumors, hematologic malignancies and some non-neoplastic diseases. The scan is more sensitive than x-ray in the detection of malignant diseases of the skeleton.

Adult

The clinical role of skeletal scanning.

Malignant disease very often spreads to the skeleton. This is particularly true for carcinomas of the breast, the lungs, the prostate, and the thyroid. Knowledge of the state of the skeleton in these disorders is therefore desirable since patient management will largely depend on the early detection of bony deposits. Primary bone disease often spreads to soft tissue (lungs), and the early detection of this may alter significantly the therapeutic approach to the primary lesion. Traditionally, X-ray skeletal surveys and serum enzyme measurements provide indices which can be used in the staging of these disorders. Complementary techniques such as mammography, xeroradiography, thermography, and radionuclide imaging have been used to provide further relevant information. A number of benign bone diseases need early assessment in order to institute the best form of treatment. It is of importance to assess the circulation in localized areas of bone and to predict the appearance of avascular necrosis, to understand the healing mechanisms involved in fractures, and to predict the outcome of bone grafting. In this paper the clinical role of bone scanning is reviewed, particular attention being given to the recent advances brought about by the introduction of the 99mTc compounds. It is important that the non-specialist should be aware of the great improvement in the results obtained and in the help they can give him in deciding on the best management of each patient as an individual.

Bone Diseases

[Skeletal scintigraphy in otolaryngology (author's transl)].

Close relation of non osseus facial skull portions to the skeleton cause rapidly the bone to become co-involved in presence of various diseases. Early diagnosis is of decisive importance for therapeutic measures. For localisation scintigraphy has proved particularly reliable in aids to early determination. This can be shown clearly in inflammatory diseases and tumour infiltrations with various tumour affections. Technical requirements and the use of skeletal scinitgraphy are demonstrated on hand of 6 cases.

Adult

[Aims and limits of nuclear medicine methods in investigation of malignant and benign bone lesions (author's transl)].

In primary bone tumors the possibilities of bone scans are discussed. Exact differentiation between malignant and benign disease by this method is impossible. However, scanning provides important information about extent of the disease, metastases, multiplicity of benign lesions and influence of adjoining diseases to the bone. A special indication exists in cases of cerebral meningiomas and an absolute indication for searching osteoplastic metastases, e.g. in carcinomas of the breast and the prostate gland.

Bone Diseases

Chromaffin cell calcium channel kinetics measured isotopically through fast calcium, strontium, and barium fluxes.

Fast Ca2+ uptake into K+-depolarized cultured bovine adrenal chromaffin cells has been isotopically measured in a time scale of 1-10 s. Depolarized cells retained as much as 80-fold 45Ca2+ taken up by resting cells; Ca2+ was not taken up by fibroblasts or endothelial-like cells. Because Ca2+ entry was inhibited by inorganic (La3+, Co2+, Mg2+) and organic (nifedipine) Ca2+ channel antagonists and enhanced by the Ca2+ channel activator Bay-K-8644, it seems clear that Ca2+ gains access to the chromaffin cell cytosol mainly through specific voltage-dependent Ca2+ channels. Ca2+ uptake evoked by 59 mM K+ was linear during the first 5 s of stimulation and continued to rise at a much slower rate up to 60 s. The rate of Ca2+ entry became steeper as the external [Ca2+] increased; initial rates of Ca2+ uptake varied from 0.06 fmol/cells . s at 0.125 mM Ca2+ to 2.85 fmol/cell . s at 7.5 mM Ca2+. The early 90Sr2+ uptake was linear but faster than Ca2+ uptake and later on was also saturated; 133Ba2+ was taken up still at a much faster rate and was linear for the entire depolarization period (2-60 s). Increased [K+] gradually depolarized chromaffin cells; Ca2+ and Sr2+ uptakes were not apparent below 30 mM K+ but were linear for 30 to 60 mM K+. In contrast, substantial Ba2+ uptake was seen even in K+-free solutions; and in 5.9 mM K+, Ba2+ uptake was as high as Ca2+ uptake obtained in 60 mM K+. Five to ten-second pulses of 45Ca2+, 90Sr2+, or 133Ba2+ given at different times after pre-depolarization of chromaffin cells served to analyze the kinetics of inactivation of the rates of entry of each divalent cation. Inactivation of Ca2+ uptake was faster than Sr2+, and Ba2+ uptake inactivated very little. Neither voltage changes nor Ca2+ ions passing through the channels seems to cause their inactivation; however, experiments aimed to manipulate the levels of internal Ca2+ using the cell-permeable chelator Quin-2 or the ionophore A23187 strongly suggest that intracellular Ca2+ levels determine the rates of inactivation of these channels.

Adrenal Gland Neoplasms

Nickel and strontium distribution in some mouse tissues. Passage through placenta and mammary glands.

Radioactive isotopes of strontium or nickel (89Sr and 63Ni) were injected ip as chlorides on adult female mice and the distribution and retention studied in several soft and hard tissues, including tissues of fetuses and sucklings. The strontium concentration was comparable in liver, kidney and heart and higher than that of brain tissue. The acid soluble part of the mineralized tissues showed a strontium concentration 100-1000 times that of the soft tissues. Progeny receiving strontium through placenta or through mammary glands showed a distribution pattern similar to that of their mother, with retention of strontium in mineralized tissue. The nickel concentration was larger in the kidney than in other organs investigated. No nickel affinity was found for mineralized tissues. Nickel was readily passed through placenta and mammary glands. Contrary to findings for strontium, the nickel concentration in tissues of fetuses was higher than that of their mother.

Animals

Changes in 87mSr concentractions in skeletal metastases in patients responding to cyclical combination chemotherapy for advanced breast cancer.

Serial 87mSr bone scintigrams were performed on a series of patients being treated by cyclical combination chemotherapy for metastatic breast cancer. All the patients investigated responeded to the chemotherapy, but initially the scintigrams showed an apparent deterioration, in that the tumor-to-normal isotope uptake ratios increased. Following this initial "flare" the scintigram appearance improved with a decrease in the tumor-to-normal uptake ratio. It is suggested that deterioration in the scintigram in the early stages of treatment should not be regarded as an indication that the patient is failing to respond.

Bone Neoplasms

Strontium 87mSr bone scanning for the evaluation of total hip replacement.

In a series of seventeen patients with unilateral osteoarthritis of the hip a scintiscanning follow-up study was made before and after total hip replacement for the assessment of the normal course of the 87mSr-scintiscan. In another series of twenty-eight patients with total hip replacement a photoscan was made as a supplement for the diagnosis of loosening of one or both components of a total hip implant. In most of these cases it proved to be a useful method, especially when clinical and raidological examination was inconclusive. It is concluded that up to six months after operation increased osteoblastic activity exists; the scintiscan became normal after that time. 87mSr scintiscanning offers a safe and simple technique for the assessment of the success and stability of total hip arthroplasty. It is also a useful aid for the early detection of loosening and infection. The procedure can help in the differential diagnosis of complaints after total hip replacement.

Arthroplasty

Strontium-87m lung scans in pulmonary aspergillosis.

Experimental observations have indicated that radioactive strontium localizes in lesions infected with Aspergillus species. Preliminary clinical studies have recommended use of strontium lung scanning to evaluate patients thought to have pulmonary manifestations of aspergillosis. In view of the difficulty in accurately interpreting the clinical significance of recovery of Aspergillus species from sputum of patients with pulmonary disorders as well as the varied clinical presentations of pulmonary aspergillosis, we have attempted to confirm these reports. Ten patients with proven pulmonary aspergillosis and five selected control subjects without aspergillosis but with other pulmonary disorders were scanned after the injection of 2-3 mCi 87mSr citrate. The strontium lung scan correlated with the chest radiograph in four of 10 patients with aspergillosis; false positive scans were found in three of five patients with other pulmonary disorders. We conclude that strontium lung scans at present have no role in the diagnostic evaluation of patients suspected of clinically significant infections with aspergillus.

Adult