Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

188Re is a radionuclide in which there is widespread interest for therapeutic purposes because of its favourable physical characteristics. Moreover, it can be eluted from an on-site installable 188W/188Re generator, which has a useful shelf-life of several months. Most of the clinical experiences gained with 188Re concern the use of 188Re-1,1-hydroxyethylidenediphosphonate (188Re-HEDP) for bone pain palliation in patients suffering prostate cancer. The maximum tolerated activity was 3.3 GBq 188Re-HEDP and if the platelet count exceeded 200 x 10(9) l(-1), the administration of 4.4 GBq appeared safe. Evidence for repeated administrations of 188Re-HEDP rather than single injections was established. In general, pain palliation occurs in 60-92% of patients with only moderate transient toxicity, mainly related to changes in blood counts. Also in haematology, radioimmunotherapy by means of 188Re might play a role by selectively targeting the bone marrow in patients undergoing conditioning prior to haematopoetic stem cell transplantation. The feasibility of such an approach was proven using a Re-labelled monoclonal antibody directed toward the CD66-antigen. More recently, encouraging safety data on locoregional treatment of primary liver tumours using 188Re-labelled lipiodol were reported. The normal organs at greatest risk for toxicity are the normal liver and the lungs. About 50% of the patients reported mild and transient side effects, mainly consisting of low grade fever, right hypochondrial discomfort or aggravation of pre-existing liver impairment. Besides the applications in oncology 188Re-based therapies have also been pioneered for benign condition such as prevention of re-stenosis following angioplasty and for radiosynovectomy in cases of refractory arthritis.
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PMID:Clinical applications of 188Re-labelled radiopharmaceuticals for radionuclide therapy. 1647 41

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

Many patients suffering from urological or non-urological malignancies develop bone metastases. One symptom often found is severe skeletal pain which siginificantly lowers the quality of life. Further symptoms are pathological fractures, spinal cord compression and hypercalcemia. The systemic radiopharmaceutical therapy represents an important systemic treatment option, in addition to chemotherapy, hormone therapy, external beam radiation, bisphosphonates and analgesics. The radionuclide therapy is rarely used and often used in a later phase of disease, mainly known for the bone pain palliation. This review article should help remind physicians to use this interesting therapy. It focuses on the common radionuclides Strontium-89-chloride, Samarium-153-EDTMP (ethylene-diamine-tetra-methylene-phosphonate) and Rhenium-186-HEDP (hydroxyethylidene-diphosphonate), their physical characteristics and differences, contraindications of the therapy like spinal cord compression and side effects. Additionally, potential tumoricidal activity and improvement of survival are discussed when using the radionuclides repetitively or in combination. The European and German guidelines are included. Furthermore, the combination of radionuclides and bisphosphonates or chemotherapy are briefly discussed, based on available clinical studies. Additionally, alpharadin (radium-223 chloride) is discussed, an experimental radiopharmaceutical under clinical evaluation, which emits alpha-radiation. In phase III clinical trials, it was shown to significantly increase the median overall survival in patients with bone metastases from advanced prostate cancer.
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PMID:[Radionuclide therapy for the treatment of skeletal metastases of urological malignancies: a forgotten therapy?]. 2287 92

Bone-targeting therapeutic radiopharmaceuticals are effective agents for treatment of painful bone metastases. Rhenium-188-HEDP is such a therapeutic radiopharmaceutical and has advantages over commercially available alternatives in terms of efficacy, safety and the ability to be produced on-site, allowing rapid treatment upon presentation of patients with pain. Unlike many other radiopharmaceuticals, there are no standardized preparation methods for Rhenium-188-HEDP. It is known, however, that drug composition may not only affect stability of the final drug product, but it may also influence bone affinity and, thus, efficacy. Furthermore, for support of clinical studies with Rhenium-188-HEDP as an investigational medicinal product, preparation of this radiopharmaceutical has to be performed under GMP conditions. To our knowledge, no group has reported on the preparation of Rhenium-188-HEDP under GMP conditions or on stock production of sterile non-radioactive starting materials. We present the production of GMP grade Rhenium-188-HEDP for application of this therapeutic radiopharmaceutical in routine clinical practice and for support of clinical studies. In addition, bio-distribution data of Rhenium-188-HEDP in mice and in patients with bone metastases originating from prostate cancer are presented.
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PMID:Bench to bedside development of GMP grade Rhenium-188-HEDP, a radiopharmaceutical for targeted treatment of painful bone metastases. 2456 Jun 35

The systemic radionuclide therapy with bone affinity substances is an effective therapy in bone palliative treatment. Studies with radiolabeled Bisphosphonate or strontium-89 show reduction of pain in 70-80% and about 20% of treated patients are pain-free. The generator product rhenium-188 represents an interesting radionuclide for bone pain palliation. It is readily available and with appropriate patient numbers is very cost-effective. Radiopharmaceuticals with Re-188 show a comparable effectiveness in bone pain palliation and bone marrow toxicity as the other known radioactive Bisphosphonate. Repeat courses of treatment with rhenium-188 HEDP even a slightly increased survival could be observed. Using therapy with alpha emitters Radium-223 in prostate cancer patients with bone metastases there was observed a prolongation of survival by 3,6 months compared with placebo. Two drugs are created in Russia on the basis of Re-188. Phosphoren is an analog of Re-188-HEDP. It showed properties similar to them in clinical studies. Complex Re-188-zoledronic acid (Zoleren) is a unique development that combines the therapeutic effect of zoledronic acid and Re-188.
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PMID:Radionuclide therapy for bone metastases by drugs based on Re-188. 3047 46


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