Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153690 (bone metastases)
6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The dynamics of uptake of osteotropic radionucleides in normal and abnormal bone were studied by means of sequential and functional scans. Various phosphate and phosphonate complexes were compared in vivo and in vitro. Only phosphonates were considered as suitable for bone scanning. In normal bones in beagles, radioactivity after HEDP fell to 65% after two hours, but was 105% with 18F. In relation to healing fractures, the curves differ quantitatively and qualitatively. In this situation, functional curves derived from dynamic scans provide a better parallel with histological findings than does static scintigraphy with an uptake quotient. Sequential and functional scanning are able to document the therapeutic effect of irradiation of bone metastases.
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PMID:[Comparative investigations of osteotropic radionucleides. IV. The dynamics of uptake in normal and abnormal bone (author's transl)]. 13 45

We have established an animal model of bone metastasis using the PC-3 human prostate tumor cell line. In order to assess whether inhibition of bone resorption would prevent the development of bone metastasis, the diphosphonate etidronate (EHDP) was administered to 20 mice at a dose of 30 mg/kg subcutaneously daily starting 2 days prior to injection of tumor cells. Control mice received daily injections of the saline vehicle. In the EHDP-treated mice, there was no significant reduction in the incidence of bone metastasis, the size of the lesions, or the number of bone lesions per mouse. Approximately 50% of the mice developed bone metastasis, which was similar to the control group and similar to what was observed in earlier studies with this animal model. Histomorphometric analysis of bones showed marked inhibition of mineralization in EHDP-treated mice, thus indicating biological effect on the bone. Therefore, the use of EHDP in biologically effective doses failed to reduce the incidence, size, or number of bone metastases in this animal model.
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PMID:Effect of etidronate disodium on the development of bone lesions in an animal model of bone metastasis using the human prostate cancer cell line PC-3. 192 62

A 77-year-old man with prostate cancer was serially evaluated for bone metastases using Tc-99m methylene disphosphonate (Tc-99m MDP) both on and off treatment with etidronate disodium (EHDP). While the patient was receiving the medication only minimal bony uptake of the tracer was seen with the majority remaining in the soft tissues. The similarly structured EHDP probably saturated the binding sites that the radioactive MDP usually adheres to. Physicians should be aware of this interaction and may have to wait until the EHDP has been discontinued for several months before performing bone imaging on these patients.
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PMID:False-negative bone imaging due to etidronate disodium therapy. 313 Oct 57

The beta emitting isotopes 186Re and 188Re are logical choices on which to base therapeutic radiopharmaceuticals that might be expected to be analogous to diagnostic radiopharmaceuticals based on 99mTc. However, the chemistry of rhenium is sufficiently different from that of technetium so that the development of Re radiopharmaceuticals often cannot be predicated on the known chemistry and biological behavior of 99mTc radiopharmaceuticals. The relevant chemical differences involve the greater stability of the higher oxidation states of Re (and thus the greater tendency of reduced Re radiopharmaceuticals to undergo re-oxidation to perrhenate), and the greater substitution inertness of reduced Re complexes. These differences are illustrated in the preparation and use of 186Re (Sn)-HEDP and 99mTc(Sn)-HEDP diphosphonate radiopharmaceuticals designed, respectively, for palliative therapy and diagnosis of metastatic cancer to bone, and in the preparation and biodistribution of tr[186Re(DMPE)2Cl2]+ and [186Re(DMPE)3]+, analogs to the potential myocardial perfusion imaging agents tr-[99mTc(DMPE)2Cl2]+ and [99mTc(DMPE)3]+. [HEDP = (1-hydroxyethylidene)diphosphonate; DMPE = 1,2-bis(dimethylphosphino)ethane].
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PMID:The chemistry of rhenium and technetium as related to the use of isotopes of these elements in therapeutic and diagnostic nuclear medicine. 379 4

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.
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PMID:Dose escalation study of rhenium-186 hydroxyethylidene diphosphonate in patients with metastatic prostate cancer. 753 Jan 99

Bone metastases can have a devastating effect on a patient's quality of life due to pain and pathologic fractures. Local external beam radiotherapy is very effective for patients with only a few involved areas. Systemic therapy consisting of chemotherapy and hormonal therapy is extremely useful until the patient becomes refractory to treatment. Systemic radionuclide therapy using Strontium-89 has been shown to be very valuable, specifically in patients with bone metastases from hormonally-resistant prostate cancer. Studies have shown a significant improvement in analgesic requirement, time to further radiotherapy, and a reduction in tumor markers with this treatment. The use of Strontium-89 in the treatment of other bone neoplasms and the use of other radionuclides, such as Rhenium-186 HEDP and Samarium-153 EDT-MP, are still investigational.
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PMID:Systemic radionuclide therapy of bone metastases with strontium-89. 816 90

Rhenium-186 (tin) hydroxyethylidene diphosphonate (186Re-HEDP), a bone-seeking radiopharmaceutical, has been successfully used in the treatment of patients with painful bone metastases. Toxicity is usually limited to reversible thrombocytopenia. An infrequent but clinically significant side effect is the occurrence of transient cranial neuropathy. We report on two prostatic cancer patients with metastatic bone cancer. Both patients developed transient cranial neuropathy shortly after treatment with 186Re-HEDP. Transient neuropathy of cranial nerves needs to be distinguished from neurological abnormalities caused by disease progression.
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PMID:Transient cranial neuropathy in prostatic cancer with bone metastases after rhenium-186-HEDP treatment. 877 46

Bone pain is a common symptom in disseminated malignancy and may be difficult to manage effectively. Radiation is of proven benefit for pain palliation and there is growing interest in the therapeutic potential of bone-seeking radiopharmaceuticals. Clinical data relating to the use of phosphorus-32, strontium-89, samarium-153 EDTMP, rhenium-186 HEDP and tin-117m DTPA are reviewed in the context of the pathophysiology of metastatic bone pain. Possible mechanisms of action of palliative radiotherapy and, in particular, the theoretical role of early response genes are discussed. The application of Monte Carlo simulation to targeted radiotherapy for bone metastases may provide the basis for a clearer understanding of the microdosimetry and radiobiology of bone pain palliation and for reliable prediction of clinical response and toxicity.
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PMID:Cancer therapy using bone-seeking isotopes. 891 78

Prostate carcinoma is the most commonly associated with osseous metastases malignancy in males. The lesions, being usually of a mixed sclerotic/lytic variety and less often of the pure sclerotic type, need to be treated by a bone seeking radioactive element with an as low as possible radiobiological burden on the surrounding (peritumoral) tissues. Rhenium-186-HEDP was used to treat these osseous metastatic lesions due to its bone seeking kinetics attractive radiochemical properties. Of a total of 16 prostate cancer patients. 3 experiment loss of pain, 8 experienced obvious and 2 some improvement. No change was observed in 3 patients. Ten patients manifested a flare syndrome increasing pain approximately 2 to 6 days, after Re-186-HEDP i.v. application. Six patients showed a definite and 9 a slight decrease in platelet levels and absolute number of polymorphonuclear white blood cells, up to fourth week following treatment. One patient underwent a whole blood transfusion and in 2 peripheral neuropathy was observed lasting about 9 to 12 days. Re-186-HEDP appears to be a promising new metal ion complex for the palliation of painful bone metastases in prostate cancer. Compared to Sr-89 therapy, it shows a longer analgetic efficacy and has the advantage of emitting gamma rays, a fact which facilitates dosimetric calculations.
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PMID:Rhenium-186-HEDP palliative treatment in disseminated bone metastases due to prostate cancer. 917 22

Recent advances in radionuclide therapy offer a new approach for the management of metastatic bone pain. This paper reports the results of dosage escalation studies with 186Re-HEDP as a bone-seeking radiopharmaceutical in patients with bone metastases originating from breast or prostate cancer with regard to toxicity, pharmacokinetics and bone marrow dosimetry and the palliating effect on bone pain. Thrombocytopenia proved to be the dose limiting factor and 186Re-HEDP showed a considerable efficacy in end-stage patients with metastatic bone pain.
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PMID:Treatment of metastatic bone pain using the bone seeking radiopharmaceutical Re-186-HEDP. 917 33


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