Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 59-year-old man with prostate cancer and pain from multiple bone metastases was treated with 1,424 MBq (38.5 mCi) rhenium-186 hydroxyethylidene diphosphonate (Re-186 HEDP). In addition, he had nonsteroidal antiandrogen, progestagen, and an analog-luteinizing hormone. Neither chemotherapy nor external-beam radiotherapy was administered. Bisphosponate therapy was stopped 4 weeks before the administration of Re-186 HEDP. The Tc-99m HMDP whole-body scan obtained 6 weeks after therapy showed the same results as before therapy. However, 1 year after therapy, a significant reduction of the mass of the metastases was visible on bone scan. The bone scan index decreased from 34 before therapy to 10 after 1 year. The patient described significant pain relief and stopped his analgesic intake 3 weeks after therapy.
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PMID:Significant reduction of the mass of bone metastasis 1 year after rhenium-186 HEDP pain palliation therapy. 1107 88

In high-activity rhenium-186 hydroxyethylidene diphosphonate ((186)Re-HEDP) treatment of bone metastatic disease from prostate cancer the dose-limiting factor is haematological toxicity. In this study, we examined the correlation of the injected activity and the whole-body absorbed dose with treatment toxicity and response. Since the best response is likely to be related to the maximum possible injected activity limited by the whole-body absorbed dose, the relationship between pre-therapy biochemical and physiological parameters and the whole-body absorbed dose was studied to derive an algorithm to predict the whole-body absorbed dose prior to injection of the radionuclide. The whole-body retention of radioactivity was measured at several time points after injection in a cohort of patients receiving activities ranging between 2,468 MBq and 5,497 MBq. The whole-body absorbed dose was calculated by fitting a sequential series of exponential phases to the whole-body time-activity data and by integrating this fit over time to obtain the whole-body cumulated activity. This was then converted to absorbed dose using the Medical Internal Radiation Dose (MIRD) committee methodology. Treatment toxicity was estimated by the relative decrease in white cell (WC) and platelet (Plt) counts after the injection of the radionuclide, and by their absolute nadir values. The criterion for a treatment response was a 50% or greater decrease in prostate-specific antigen (PSA) value lasting for 4 weeks. Alkaline phosphatase (AlkPh), chromium-51 ethylene diamine tetra-acetate ((51)Cr-EDTA) clearance rate and weight were measured before injection of the radionuclide. The whole-body absorbed dose showed a significant correlation with WC and Plt toxicity ( P=0.005 and 0.003 for the relative decrease and P=0.006 and 0.003 for the nadir values of WC and Plt counts respectively) in a multivariate analysis which included injected activity, whole-body absorbed dose, pre-treatment WC and Plt baseline counts, PSA and AlkPh values, and the pre-treatment Soloway score. The injected activity did not show any correlation with WC or Plt toxicity, but it did correlate with PSA response ( P=0.005). These results suggest that the administration of higher activities would be likely to generate a better response, but that the quantity of activity that can be administered is limited by the whole-body absorbed dose. We have derived and evaluated a model that estimates the whole-body absorbed dose on an individual patient basis prior to injection. This model uses the level of injected activity and pre-injection measurements of AlkPh, weight and (51)Cr-EDTA clearance. It gave good estimates of the whole-body absorbed dose, with an average difference between predicted and measured values of 15%. Furthermore, the whole-body absorbed dose predicted using this algorithm correlated with treatment toxicity. It could therefore be used to administer levels of activity on a patient-specific basis, which would help in the optimisation of targeted radionuclide therapy. We believe that algorithms of this kind, which use pre-injection biochemical and physiological measurements, could assist in the design of escalation trials based on a toxicity-limiting whole-body absorbed dose, rather than using the more conventional activity escalation approach.
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PMID:A model-based method for the prediction of whole-body absorbed dose and bone marrow toxicity for 186Re-HEDP treatment of skeletal metastases from prostate cancer. 1276 96

Concerning bone and joint diseases therapy of rheumatic synovitis (= radiosynoviorthesis) was introduced in 1952 before clinically relevant diagnostic procedures were developed. Radionuclides of Sr and later on 99mTc phosphonates then started the wide use of bone scintigraphy since > 30 years. The diagnostic methods have an excellent sensitivity for detection of local abnormalities of bone metabolism, the specificity of such studies, however, is low. Modifications of the technique (3-phase-bone-scintigraphy, pinhole collimators, ROI-technique), increasing knowledge of pathological scan patterns and introduction of other radionuclide studies (67Ga, 201Tl, inflammation scans with 99mTc-leukocytes or 99mTc-HIG) as well as 18FDG-PET have increased the specificity significantly in recent years and improvements of imaging systems (SPECT) also increased the accuracy of diagnostic methods in diseases of bone and joints. Therapy of such diseases has made considerable progress: inflamed, swollen joints can effectively be treated with 90Y-, 186Re, 169Er-colloids or with 165Dy-particles by radiosynoviorthesis. Severe pain due to disseminated bone metastases of cancer or polyarthritis can be controlled by radionuclide therapy with 89Sr, 153Sm-EDTMP, 186Re- or 188Re-HEDP and possibly 117mSn-DTPA with an acceptable risk of myelodepression. Possibilities, technical details and limitations of radionuclide applications for diagnostic and therapeutic purposes must be considered if optimal benefit for individual patients should be achieved. Overall Nuclear Medicine can become an essential element in management of bone and joint diseases. The relationship of Nuclear Medicine to bone and joint pathology is peculiar: In 1952 treatment of rheumatic synovitis by radiosynoviorthesis with 198Au Colloid was started by Fellinger and Schmid before diagnostic approaches to bone pathology existed. Bone scintigraphy was introduced only in 1961 using 85Sr but obviously the unfavourable radiation characteristics of this radionuclide limited it's broad application and 87mSr did not improve this situation. Only when 99mTc phosphonates were developed by Subramanian the importance of bone scintigraphy became apparent: The excellent imaging properties of these radiotracers showed, that abnormal bone metabolism could be visualized even before morphological alterations in the skeleton become visible on radiographies or even CT-scans. Moreover, proposals made earlier to use 32P or 89Sr for palliation of pain in patients with disseminated skeletal metastases were picked up again and led also to other radiopharmaceuticals (186Re-HEDP, 153Sm-EDTMP, 117mSn-DTPA) which are applied today for the same purpose with very good success. Therefore Nuclear Medicine today has a broad program for diagnostic and therapeutic approaches to diseases of bone and joints. In bone scanning the high sensitivity led to inclusion of this method for routine staging and re-staging programs in a variety of cancer forms which have a trend to develop bone metastases (e.g. breast, lung, prostate, melanoma) but the low specificity of abnormal patterns on such scans can impair the diagnostic value of the technique. To increase specificity and to define inflammatory lesions, radiotracers used for "inflammation scanning" were introduced such as labeled granulocytes, 99mTc Human Immunoglobulin and others but also a simple modification of bone scanning--triple phase bone scintigraphy--was used. Recently the excellent properties of 18F for PET of the skeleton were rediscovered again and emission CT scanning--possibly with overlay with transmission CT or MRT pictures--can enhance the diagnostic impact of radionuclide bone studies.
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PMID:Nuclear medicine in diagnosis and therapy of bone and joint diseases. 1460 Oct

Rhenium-188-hydroxyethylidine diphosphonate (188Re-HEDP) is a novel and attractive radiopharmaceutical that localizes in areas of osseous metastases and emits beta particles with energy sufficient to be therapeutically useful. The aim of this study is to evaluate the effectiveness of 188Re-HEDP in patients with lung cancer for the palliation of painful osseous metastases. Intravenous administration of activities ranging between 1.15 GBq (31 mCi) and 4.6 GBq (124 mCi) of 188Re-HEDP was given to each of 30 patients with painful osseous metastases from lung cancer. The patients were clinically followed at weekly intervals for the first 2 months, and monthly thereafter up to 1 year. Hematologic testing was performed before treatment and thereafter for 6 weeks. Pain response was scored by a four-point pain-rating scale as complete, marked, mild, and no response. Prompt and significant relief of bone pain occurred in 80% with no significant side-effects or hematopoietic toxicity. Forty-six percent (46%) of the patients discontinued analgesics after treatment. This clinical study indicated that 188Re-HEDP can offer significant pain palliation and is a useful radiopharmaceutical for treating painful osseous metastases from lung cancer.
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PMID:Rhenium-188-HEDP therapy for the palliation of pain due to osseous metastases in lung cancer patients. 1462 20

Patients with skeletal metastases from hormone-refractory prostate cancer have shown variable responses to high-activity therapy with (186)Re-HEDP and peripheral stem cell support. In this paper, we report on the use of a novel technique to compare sequential planar images acquired post-(186)Re-HEDP therapy administration with pretherapy diagnostic (99m)Tc-MDP scans, to evaluate the turnover of the radiopharmaceutical in normal and abnormal bone. It was found that the activity in normal (i.e., disease-free) segments of the spine demonstrates a faster effective decay than that of the metastases, with the latter showing only physical decay. This study showed, for the first time, a detailed correlation in the behavior of the (99m)Tc-MDP and (186)Re-HEDP images, encouraging the possibility of using the pretherapy 99mTc-MDP scan for estimations of absorbed doses to be delivered by prescribed activities of (186)Re-HEDP.
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PMID:The potential use of 99mTc-MDP bone scans to plan high-activity 186Re-HEDP targeted therapy of bony metastases from prostate cancer. 1586 54

Etidronate is an oral bisphosphonate compound that is known to reduce bone resorption through the inhibition of osteoclastic activity. The efficacy of etidronate for involutional (postmenopausal and senile) and glucocorticoid-induced osteoporosis, as well as that for other skeletal diseases, was reviewed in Japanese patients. Cyclical etidronate treatment (200 mg or 400mg/day for 2 weeks about every 3 months) increases the lumbar bone mineral density (BMD) in patients with involutional osteoporosis and prevents incident vertebral fractures in patients with glucocorticoid-induced osteoporosis. The losses of the lumbar BMD in patients with liver cirrhosis and the metacarpal BMD in hemiplegic patients after stroke are prevented, and the lumbar BMD is possibly increased, preventing fragile fractures in adult patients with osteogenesis imperfecta type I. Furthermore, proximal bone resorption around the femoral stem is reduced and some complications may be prevented in patients who undergo cementless total hip arthroplasty. Oral etidronate treatment may also help to transiently relieve metastatic cancer bone pain followed by a decrease in abnormally raised bone resorption in patients with painful bone metastases from primary cancer sites, such as the lung, breast and prostate. Thus, oral etidronate treatment is suggested to be efficacious for osteoporosis, as well as other skeletal diseases associated with increased bone resorption, in Japanese patients. Randomized controlled trials needed to be conducted on a large number of patients to confirm these effects.
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PMID:Efficacy of oral etidronate for skeletal diseases in Japan. 1598 1

Many patients with cancer develop symptomatic skeletal metastases at an advanced stage of their disease. Skeletal metastases are often complicated by pain. They cause considerable morbidity and mortality. Besides analgesics, treatment options include external beam radiotherapy, bisphosphonates, chemotherapy, surgery and bone seeking radiopharmaceuticals. Pain palliation with bone seeking radiopharmaceuticals has proved to be an effective treatment modality in patients with metastatic bone pain. Radiopharmaceuticals bind to the bone matrix in areas of increased bone turnover, due to a metastatic response. Beta rays from the specific radionuclide, bound to its carrier ligand, result in the therapeutic effect. Various radiopharmaceuticals have been developed for this purpose. All have their own characteristics. The radiopharmaceuticals Samarium-153-ethylenediaminetetramethylenephosphonic acid ((153)Sm-EDTMP) and Strontium-89-Chloride, which are approved in the USA and Europe, as well as the not universally approved Rhenium-186-hydroxyethylidenediphosphonic acid ((186)Re-HEDP), will be discussed in greater detail. Depending on the half-life and radiation energy of the specific radionuclide, they exert a different effect and toxicity profile. In most cases, bone marrow toxicity is limited and reversible, which makes repetitive treatment relatively safe. Several studies have shown encouraging clinical results of palliative therapy using bone seeking radiopharmaceuticals, with an overall reported pain response rate in the order of +/- 70-80% of patients. This systemic form of radionuclide therapy is simple to administer and complements other treatment options. It has been associated with marked pain reduction, improved mobility in many patients, reduced dependence on analgesics, and improved performance status and quality of life. Additionally, new therapeutic strategies hold the promise of enhancement of the palliative and anticancer effects of this form of therapy.
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PMID:Bone seeking radiopharmaceuticals for palliation of pain in cancer patients with osseous metastases. 1763 Sep 15

The skeleton is one of the most common organs affected by metastatic cancer, and bone metastases often cause severe pain, which significantly affects quality of life. Internal radiotherapy using specifically localized bone-seeking radiopharmaceuticals has proven to be an effective alternative and shows fewer side effects than those associated with other forms of treatment. In this review article, we highlight not only radiopharmaceuticals, which have been approved for the palliation of bone metastases but also boneseeking radiolabeled compounds under investigation in basic research. Specifically, we review the efficacy and prospects of phosphorus- 32, strontium-89 chloride, samarium-153-EDTMP, rhenium-186/188-HEDP, rhenium-186/188-complex conjugated bisphosphonate compounds, yttrium-90-DOTA conjugated bisphosphonate, rhenium-186/188-DMSA, radium-223 chloride, thorium-227-EDTMP, thorium-227-DOTMP, and lead/bismuth-212-DOTMP.
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PMID:Bone target radiotracers for palliative therapy of bone metastases. 2266 47


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