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)

Etidronate and medronate have been labelled with technetium-99m (99mTc-HEDP, 99mTc-MDP) for bone scanning and, with rhenium-188 (188Re-HEDP) to palliate the pain resulting from bone metastases. The objective of this study was to label alendronate, ABP, a new bisphosphonate, with SnF2-reduced-188Re. The reagents for the 5 mg ABP kit were SnF2, KReO4 and gentisic acid at acid pH. The chemical, spectroscopic and microscopic characteristics, quality control, rat bone uptake of [188Re]Re-ABP and similarities with 99mTc-ABP are presented. We conclude that this is a promising new radiopharmaceutical for bone metastases pain palliation.
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PMID:Labelling of Re-ABP with 188Re for bone pain palliation. 1121 78

BACKGROUND: A study for pain relief therapy with 188Re-HEDP was done in patients with bone metastases secondary to breast and prostate cancer. MATERIALS AND METHODS: Patients received 1.3 or 2.2 GBq, in single or multiple doses. Platelets, white and red cells were evaluated during 11 weeks. Pharmacokinetic characterization was done from blood and urine samples for 5 patients along 24 hours. Urinary excretion was evaluated in other 16 patients during 6 hours. Bone uptake was estimated as remaining activity in whole body. Scintigraphic images were acquired at 2 and 24 hs post-administration. Absorbed dose in bone marrow was estimated with Mirdose3. Analgesics intake and pain score were daily recorded. Tumour markers (PSA, and Tn-structure) were monitored in 9 patients during 4 to 6 months. Single doses of low activity (1.3 GBq) were given to twelve patients. Nine patients received multiple doses. RESULTS: All except one patient had normal levels of platelets, white and red cells. Remaining dose in blood at 2 hours was 9%. Urinary elimination was 58%. Bone uptake at 24 hours was 43% (mean value; n = 5). No changes of the haematological parameters were detected along follow-up period. Pain relief was evidenced by decrease or supression of opioid analgesic and by subjective index. PSA showed a decrease in prostate cancer patients (n = 4). Tn-structure showed a significant increase after 4 to 8 months. CONCLUSION: Single or multiple dose scheme could be safely used, with administered activity of 188Re-HEDP up to 60 mCi, with low bone marrow absorbed doses.
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PMID:Re-HEDP : pharmacokinetic characterization, clinical and dosimetric evaluation in osseous metastatic patients with two levels of radiopharmaceutical dose. 1173 69

Rhenium-188-HEDP ((188)Re-HEDP) is a new and attractive radiopharmaceutical for the treatment of metastatic bone pain. As a product of (188)W/(188)Re generator, it is convenient for clinical therapeutic use with a short physical half-life of 16.9 h and a maximal beta-energy of 2.1 MeV. We investigated the effect of (188)Re-HEDP on pain relief, analgesic intake and impairment of bone marrow function in 27 patients with bone metastases induced from prostate cancer. All patients were interviewed using a standardised set of questions before, and after therapy for 12 weeks. The patients were treated with 2700-3459 MBq of (188)Re-HEDP. Blood samples were taken weekly for 12 weeks, and a blood count was performed. Patients described an improvement on the Karnofsky performance scale from 74+/-7 to 85+/-9% 12 weeks after therapy (P=0.001). The pain score showed a maximum decrease from 44+/-18 to 27+/-20% in the third to the eight week after therapy (P=0.009). Seventy-six percent of the patients described a pain relief without increase of analgesic intake. Twenty percent of the patients could discontinue their analgesics and were pain free. Mean platelet count decreased from (286+/-75)*10(3) microl(-1) to (215+/-92)*10(3) microl(-1), and mean leucocyte count from (7.7+/-1.5)*10(3) microl(-1) to (6.0+/-1.9)*10(3) microl(-1) in the second to the fourth week after therapy. The maximal differences between the values of platelets and leucocytes before and after therapy were not statistically significant (P=0.021 and 0.094). In conclusion, (188)Re-HEDP is an effective radiopharmaceutical used in the palliative treatment of metastatic bone pain in prostate cancer and shows minimal bone marrow toxicity.
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PMID:Therapeutic efficiency of rhenium-188-HEDP in human prostate cancer skeletal metastases. 1291 68

Radionuclide bone metastases therapy is a major achievement of nuclear medicine. Development of less radiotoxic and more effective radiopharmaceuticals is therefore a challenge for radiopharmacists and industry. This paper reviews the application of rhenium-188 HEDP as a reactor- or generator-produced nuclide for bone metastases therapy.
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PMID:Application of rhenium-188 HEDP in bone metastases therapy. 1460 Sep 35

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

Bone is a preferred site of metastasis for many solid tumors, and the complications associated with bone metastases can result in significant skeletal morbidity including severe bone pain, pathologic fracture, spinal cord compression, and hypercalcemia of malignancy (HCM). Bisphosphonates are the current standard of care for preventing skeletal complications associated with bone metastases. Clinical trials investigating the benefit of bisphosphonate therapy have used a composite end point defined as a skeletal-related event (SRE) or bone event, which typically includes pathologic fracture, spinal cord compression, radiation or surgery to bone, and HCM. Bisphosphonates have been shown to significantly reduce the incidence of these events in patients with bone metastases. Zoledronic acid (Zometa; Novartis Pharmaceuticals Corp.; East Hanover, NJ), pamidronate (Aredia; Novartis Pharmaceuticals Corp.), clodronate (Bonefos; Anthra Pharmaceuticals; Princeton, NJ), and ibandronate (Bondronat; Hoffmann-La Roche Inc.; Nutley, NJ) all have demonstrated efficacy superior to that of placebo in patients with breast cancer. Zoledronic acid is the only bisphosphonate that has been compared directly with pamidronate, and it was shown by multiple event analysis to be significantly more effective at reducing the risk of an SRE. In patients with prostate cancer, clodronate, etidronate (Didronel; Procter and Gamble Pharmaceuticals, Inc.; Cincinnati, OH), and pamidronate have demonstrated transient palliation of bone pain. However, zoledronic acid is the only bisphosphonate to demonstrate both significant and sustained pain reduction and a significantly lower incidence and longer time to onset of SREs compared with placebo. Zoledronic acid is also the only bisphosphonate to demonstrate efficacy in patients with bone metastases from a variety of other solid tumors, including lung cancer and renal cell carcinoma. In conclusion, bisphosphonates effectively reduce skeletal complications in patients with bone metastases from breast cancer, and zoledronic acid has demonstrated the broadest clinical activity in patients with a wide variety of tumor types.
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PMID:Bisphosphonates: clinical experience. 1545 26

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

Several radiopharmaceuticals were investigated to determine their efficacy and toxicity in the palliation of painful bone metastases. Data on the influence of rhenium-188 hydroxyethylidene diphosphonate (188Re-HEDP), rhenium-186 hydroxyethylidene diphosphonate (186Re-HEDP), and strontium-89 (89Sr) on pain symptoms, quality of life, and bone-marrow function were obtained in 64 patients with breast and prostate cancer. Thirty-one patients were treated with 188Re-HEDP (3194 +/- 387 MBq), 15 patients with 186Re-HEDP (1358 +/- 158 MBq), and 18 patients with 89Sr (152 +/- 19 MBq). The 188Re-HEDP group included six breast cancer patients and 25 prostate cancer patients; the 186Re-HEDP group included three breast cancer patients and 12 prostate cancer patients; and the 89Sr group included three breast cancer patients and 15 prostate cancer patients. All subjects participated in an interview using a standardized sets of questions before and after the 12-week term of therapy. Blood counts were taken weekly for six weeks and after 12 weeks. Results showed that 77 percent of patients reported pain relief after treatment with 188Re-HEDP, 67 percent after treatment with 186Re-HEDP, and 72 percent after treatment with 89Sr. Sixteen percent of patients treated with 188Re-HEDP, 13 percent treated with 186Re-HEDP, and 17 percent treated with 89Sr were able to discontinue their analgesics and were pain-free. Patients described an improvement on Karnofsky performance status (KPS) from 73 +/- 7 percent to 85 +/- 8 percent 12 weeks after 188Re-HEDP (p < 0. 05), from 72 +/- 13 percent to 79 +/- 12 percent after 186Re-HEDP (p = 0.251), and from 62 +/- 14 percent to 69 +/- 16 percent after 89Sr (p = 0.415). Only three patients undergoing 188Re-HEDP therapy, one undergoing 186Re-HEDP therapy, and three undergoing 89Sr therapy had thrombocytopenia (platelet count below 100 x 10(3)/microl) following treatment. The maximum nadir of platelet and leukocyte counts was observed between the second and fifth week after treatment for all radionuclides and was reversible within 12 weeks. The nadir was earlier for 188Re-HEDP with a shorter physical half-life compared with 89Sr. There were no significant differences in bone marrow toxicity (p = 0.123-0.421). Results of this study indicate that all evaluated radiopharmaceuticals were effective in pain palliation without induction of severe side effects. The increase in KPS after 188Re-HEDP was the only statistically significant finding (p = 0.001).
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PMID:Systemic radionuclide therapy in pain palliation. 1632 16

The aim of this work was to estimate tumor-absorbed doses delivered from the administration of fixed activities of (186)Re-HEDP for the treatment of bone metastases from prostate cancer. The variations and reproducibility in the estimated absorbed dose owing to the reconstruction algorithm used (OSEM vs. FBP) were also analysed. For this aim, correction methods for scatter and attenuation were kept identical, whereas the same calibration data and thresholding techniques were used to obtain quantification. This study was carried out in spinal and pelvic lesions of 7 patients. For comparison, the absorbed doses, based upon the maximum and the mean voxel count, were calculated, resulting in the absorbed dose (maximum): 60 Gy (sigma = 30 Gy) and 33 Gy (sigma = 15 Gy) for OSEM and FBP, respectively, and absorbed dose (mean): 26 Gy (sigma = 12 Gy) and 17 Gy (sigma = 7 Gy) with OSEM and FBP, respectively. We concluded that the administration of fixed activity resulted in a range of absorbed doses, and we showed that, despite using the same approach, the choice of the reconstruction algorithm can result in differences higher than 50% in the estimated tumor-absorbed doses. In conclusion, the need for a standardization of the methodology used for the calculations is emphasized by this work, especially when comparisons between patients and different centers are of interest.
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PMID:Tumor dosimetry on SPECT (186)Re-HEDP scans: variations in the results from the reconstruction methods used. 1762 20

Men with prostate cancer initiating androgen-deprivation therapy (ADT) may have multiple factors that threaten their skeletal health, including increased fracture risk from bone loss during ADT and the propensity to develop bone metastases, which may lead to skeletal-related events (SREs). Bisphosphonates have utility in oncology for patients with bone metastases to prevent bone loss during hormonal therapy and in the benign setting to treat osteoporosis. These agents have an emerging role in patients with hormone-sensitive prostate cancer (HSPC). Etidronate, alendronate, pamidronate, and zoledronic acid have all shown efficacy in preventing ADT-related bone loss. Alendronate and zoledronic acid have also been shown to increase bone mineral density vs baseline during ADT. Patients with bone metastases from HSPC who received 4 mg zoledronic acid every 3 or 4 weeks had a low incidence of skeletal complications, although controlled study data have not been reported. Bisphosphonate treatment in men with HSPC may be effective for the prevention of ADT-related bone loss, underscoring the importance of treating early to avoid SREs and potentially delay disease progression to metastatic bone disease.
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PMID:Preserving bone health in patients with hormone-sensitive prostate cancer: the role of bisphosphonates. 2005 88


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