Europium radionuclides in samarium-153-Ethylene Diamine Tetramethylene phosphonic acid (153Sm-EDTMP) radiopharmaceutical waste.

153Sm-EDTMP is widely used as a palliative radiopharmaceutical for treatment of metastatic bone pain. It is produced by neutron activation of enriched 152Sm targets in a nuclear reactor. The long-lived europium radionuclides are co-produced along with production of 153Sm and it give rise to radioactive waste in 153Sm-EDTMP production. The gamma radiation dose rate was found significant on the radioactive waste generated during the production of 153Sm-EDTMP. Residual activity in six waste samples generated in different batches of 153Sm-EDTMP production were analysed for percentage contributions of 152,154,155Eu using gamma-ray spectrometry. 154Eu was a major contributor with around 62%, and the other radioisotopes, viz. 152Eu &155Eu contribution were ∼29% & ∼9% respectively. The activity concentration of these long-lived europium radionuclides in samarium radiopharmaceutical production waste may be utilised for the dose rate estimation, and vice versa.

In silico dosimetry of low-dose rate brachytherapy using radioactive nanoparticles.

PURPOSE: Nanoparticles (NPs) with radioactive atoms incorporated within the structure of the NP or bound to its surface, functionalized with biomolecules are reported as an alternative to low-dose-rate seed-based brachytherapy. In this study, authors report a mathematical dosimetric study on low-dose rate brachytherapy using radioactive NPs. METHOD: Single-cell dosimetry was performed by calculating cellular S-values for spherical cell model using Au-198, Pd-103 and Sm-153 NPs. The cell survival and tumor volume versus time curves were calculated and compared to the experimental studies on radiotherapeutic efficiency of radioactive NPs published in the literature. Finally, the radiotherapeutic efficiency of Au-198, Pd-103 and Sm-153 NPs was tested for variable: administered radioactivity, tumor volume and tumor cell type. RESULT: At the cellular level Sm-153 presented the highest S-value, followed by Pd-103 and Au-198. The calculated cell survival and tumor volume curves match very well with the published experimental results. It was found that Au-198 and Sm-153 can effectively treat highly aggressive, large tumor volumes with low radioactivity. CONCLUSION: The accurate knowledge of uptake rate, washout rate of NPs, radio-sensitivity and tumor repopulation rate is important for the calculation of cell survival curves. Self-absorption of emitted radiation and dose enhancement due to AuNPs must be considered in the calculations. Selection of radionuclide for radioactive NP must consider size of tumor, repopulation rate and radiosensitivity of tumor cells. Au-198 NPs functionalized with Mangiferin are a suitable choice for treating large, radioresistant and rapidly growing tumors.

Knee radiosynovectomy with 153Sm-hydroxyapatite compared to 90Y-hydroxyapatite: initial results of a prospective trial.

INTRODUCTION: Radiosynovectomy (RS) with 90Y-hydroxyapatite (90Y-HyA) aims to control knee hemarthrosis in hemophiliac patients to prevent secondary arthropathy. However, knee RS using 153Sm-hydroxyapatite (153Sm-HyA) is considered less suitable due to the lower average soft tissue range and energy of 153Sm for large joints, such as the knees. PURPOSE: The objective of this investigation was to assess the efficacy and safety of knee RS with 153Sm-HyA, compared to 90Y-HyA. METHODS: Forty patients were prospectively assigned to undergo knee RS with 153Sm-HyA (n = 19) or with 90Y-HyA (n = 21). The frequency of hemarthrosis episodes before and after treatment were compared. RESULTS: After six months of knee RS, 153Sm-HyA and 90Y-HyA promoted a similar reduction of hemarthrosis episodes (50% and 66.7%, respectively). However, after 12 months of knee RS, the reduction of hemarthrosis episodes was significantly (p = 0.037) higher using 153Sm-HyA (87.5%) compared to 90Y-HyA (50.0%). This discrepancy was more pronounced (p = 0.002) for 153Sm-HyA compared to 90Y-HyA in adults/adolescents. CONCLUSION: Knee radiosynovectomy with 153Sm-HyA is safe, reduces hemarthrosis episodes after 12 months of treatments, especially in adults/adolescents and even with grades III/IV arthropathy, similar to 90Y-HyA. 90Y-HyA seems to promote better hemarthrosis control in small children.

Osteochondrodysplasia in a Scottish Fold Cat Treated with Radiation Therapy and Samarium-153-1,4,7,10-Tetraazacyclododecane-1,4,7,10-Tetramethylene-Phosphonic Acid.

Osteochondrodysplasia is a painful, progressive clinical syndrome unique to Scottish fold cats because of a heritable missense mutation in the TRPV4 gene. An 8 yr old male neutered Scottish fold cat was presented for a mass on his hind paw. The mass caused decreased mobility in the metatarsal region and digits and resulted in significant discomfort. Because of extensive skeletal abnormalities attributed to breed-related osteochondrodysplasia, the owner was reluctant to pursue amputation. Radiation therapy was pursued for palliation of pain. After coarsely fractionated external beam radiotherapy resulted in stabilization of the mass with eventual progression after 14 mo, samarium-153-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid was administered systemically, and the cat showed immediate, whole-body improvement in mobility. Concurrent intestinal and respiratory disease was evaluated and managed. Samarium-153-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid administration was repeated approximately every 6 mo for three treatments until the cat succumbed to thromboembolic disease attributed to previously diagnosed cardiac disease. Radiation therapy administered using either external beam or bone-seeking radioisotopes can be effective at palliating clinical signs associated with the skeletal abnormalities that accompany this disease.

Bone-targeted therapies to reduce skeletal morbidity in prostate cancer.

Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA. Denosumab has shown enhanced delay in skeletal-related events compared to zoledronic acid in patients with metastatic castration-resistant prostate cancer (mCRPC). Data are mixed with regard to pain control as a primary measure of efficacy. New data call into question dosing frequency, with quarterly dosing strategy potentially achieving similar effect compared to monthly dosing for zoledronic acid. In the case of radium-223, there are data for both pain palliation and improved overall survival in mCRPC. Further studies are needed to optimize timing and combination strategies for bone-targeted therapies. Ongoing studies will explore the impact of combining bone-targeted therapy with investigational therapeutic agents such as immunotherapy, for advanced prostate cancer. Future studies should strive to develop biomarkers of response, in order to improve efficacy and cost-effectiveness of these agents.

An electrochemical approach for removal of radionuclidic contaminants of Eu from 153Sm for effective use in metastatic bone pain palliation.

INTRODUCTION: Thermal neutron activation of 152Sm [152Sm(n,γ)153Sm] using natural or isotopically enriched (by 152Sm) samarium target is the established route for production of 153Sm used for preparation of 153Sm-EDTMP for pain palliation in cancer patients with disseminated bone metastases. However, some long-lived radionuclidic contaminants of Eu, such as, 154Eu (t½=8.6y) are also produced during the target activation process. This leads to detectable amount of Eu radionuclidic contaminants in patients' skeleton even years after administration with therapeutic doses of 153Sm-EDTMP. Further, the presence of such contaminants in 153Sm raises concerns related to radioactive waste management. The aim of the present study was to develop and demonstrate a viable method for large-scale purification of 153Sm from radionuclidic contaminants of Eu. METHODS: A radiochemical separation procedure adopting electroamalgamation approach has been critically evaluated. The influence of different experimental parameters for the quantitative removal radionuclidic contaminants of Eu from 153Sm was investigated and optimized. The effectiveness of the method was demonstrated by purification of ~37 GBq of 153Sm in several batches. As a proof of concept, 153Sm-EDTMP was administered in normal Wistar rats and ex vivo γ-spectrometry of bone samples were carried out. RESULTS: After carrying out the electrolysis under the optimized conditions, the radionuclidic contaminants of Eu could not be detected in purified 153Sm solution by γ-spectrometry. The overall yield of 153Sm obtained after the purification process was >85%. The reliability of this approach was amply demonstrated in several batches, wherein the performance remained consistent. Ex vivo γ-spectrometry of bone samples of Wistar rats administered with 153Sm-EDTMP (prepared using electrochemically purified 153Sm) did not show photo peaks corresponding to radionuclidic contaminants of Eu. CONCLUSIONS: A viable electrochemical strategy for the large-scale purification of 153Sm from radionuclidic contaminants of Eu has been successfully developed and demonstrated.

Efficacy and safety of 153Sm-EDTMP as treatment of painful bone metastasis: a large single-center study.

PURPOSE: The purpose of this study is to assess the efficacy of 153Sm-EDTMP (Quadramet®) in a clinical setting. METHODS: We have conducted a retrospective study of all consecutive patients (pts) treated with 153Sm-EDTMP for painful bone metastases. At each visit (before and after treatment), four parameters were collected: (i) pain assessment according to the 10-step visual analogue scale (VAS), (ii) sleep disturbance related to pain, (iii) dose of analgesic medication, and (iv) answer to the following closed question "Do you think you obtained a benefit from treatment?" Success of treatment was defined by the combination of these four parameters. RESULTS: Three hundred seventy consecutive 153Sm-EDTMP treatments for painful bone metastases were given. Patients had the following primary tumors: breast carcinoma (153), prostate carcinoma (155), lung carcinoma (27), or other cancers (35). Fifty-eight percent of the patients had received previous external osseous radiotherapy. Ninety-seven percent of the patients were treated with concomitant analgesics and 61% were treated with diphosphonates. A clinical benefit was described in 55.0% of cases at D30. Treatment was more effective in cases of breast and prostate cancers compared with other types of primary cancers. Patients described a benefit at D30 in 62, 58, 6, and 38% of cases of breast, prostate, lung, and other cancers. The subjective efficacy was accompanied by a decrease in analgesic intake in 35.0% of cases. CONCLUSION: 153Sm-EDTMP therapy is an effective supportive treatment in patients who suffer from bone metastases, especially in patients with breast or prostate cancer.

Dosimetry in Radiosynoviorthesis: 90Y VS. 153Sm.

Although there are several radionuclides suitable for radiosynoviorthesis (RSO), not all of them can irradiate deeper synovium. Yttrium-90 (Y) is the beta radionuclide with more penetration range; therefore, it is predominantly used to treat knees. The aim of this paper is to highlight several dosimetry concepts to compare Y and Sm, also discussing the feasibility of implementing a dose planning methodology for both in RSO. The MCNPX Monte Carlo nuclear code version 2.6 was used for calculating S-values from which the activity to be injected into the joint was obtained. This activity is considered sufficient to deliver a 100-Gy absorbed dose in 1 mm of synovial tissue. The simulated mathematical model consisted of a system formed by several cylindrical slabs of 1-mm thickness, aligned consecutively. The different areas of the cylinder base simulate several synovial membrane sizes. The effective treatment range for each radionuclide was also calculated. Quantification of the synovial joint features (synovial thickness and synovial surface) by diagnostic imaging, such as magnetic resonance (MRI) combined with a Monte Carlo simulation, can be used to achieve a treatment planning strategy in RSO with the available radionuclides.

WITHDRAWN: Radioisotopes for metastatic bone pain.

BACKGROUND: This is an update of the review published in Issue 4, 2003. Bone metastasis cause severe pain as well as pathological fractures, hypercalcaemia and spinal cord compression. Treatment strategies currently available to relieve pain from bone metastases include analgesia, radiotherapy, surgery, chemotherapy, hormone therapy, radioisotopes and bisphosphonates. OBJECTIVES: To determine efficacy and safety of radioisotopes in patients with bone metastases to improve metastatic pain, decrease number of complications due to bone metastases and improve patient survival. SEARCH METHODS: We sought randomised controlled trials (RCTs) in MEDLINE, EMBASE, CENTRAL, and the PaPaS Trials Register up to October 2010. SELECTION CRITERIA: Studies selected had metastatic bone pain as a major outcome after treatment with a radioisotope, compared with placebo or another radioisotope. DATA COLLECTION AND ANALYSIS: We assessed the risk of bias of included studies by their sequence generation, allocation concealment, blinding of study participants, researchers and outcome assessors, and incomplete outcome data. Two review authors extracted data. We performed statistical analysis as an "available case" analysis, and calculated global estimates of effect using a random-effects model. We also performed an intention-to-treat (ITT) sensitivity analysis. MAIN RESULTS: This update includes 15 studies (1146 analyzed participants): four (325 participants) already included and 11 new (821 participants). Only three studies had a low risk of bias. We observed a small benefit of radioisotopes for complete relief (risk ratio (RR) 2.10, 95% CI 1.32 to 3.35; Number needed to treat to benefit (NNT) = 5) and complete/partial relief (RR 1.72, 95% CI 1.13 to 2.63; NNT = 4) in the short and medium term (eight studies, 499 participants). There is no conclusive evidence to demonstrate that radioisotopes modify the use of analgesia with respect to placebo. Leucocytopenia and thrombocytopenia are secondary effects significantly associated with the administration of radioisotopes (RR 5.03; 95% CI 1.35 to 18.70; Number needed to treat to harm (NNH) = 13). Pain flares were not higher in the radioisotopes group (RR 0.74; 95% CI 0.27 to 2.06). There are scarce data of moderate quality when comparing Strontium-89 (89Sr) with Samarium-153 (153Sm), Rhenium-186 (186Re) and Phosphorus-32 (32P). We observed no significant differences between treatments. Similarly, we observed no differences when we compared different doses of 153Sm (0.5 versus 1.0 mCi). AUTHORS' CONCLUSIONS: This update adds new evidence on efficacy of radioisotopes versus placebo, 89Sr compared with other radioisotopes, and dose-comparisons of 153Sm and 188Re. There is some evidence indicating that radioisotopes may provide complete reduction in pain over one to six months with no increase in analgesic use, but severe adverse effects (leucocytopenia and thrombocytopenia) are frequent.

The importance of BMI in dosimetry of 153Sm-EDTMP bone pain palliation therapy: A Monte Carlo study.

Using digital phantoms as an atlas compared to acquiring CT data for internal radionuclide dosimetry decreases patient overall radiation dose and reduces the required analysis effort and time for organ segmentation. The drawback is that the phantom may not match exactly with the patient. We assessed the effect of varying BMIs on dosimetry results for a bone pain palliation agent, 153Sm-EDTMP. The simulation was done using the GATE Monte Carlo code. Female XCAT phantoms with the following different BMIs were employed: 18.6, 20.8, 22.1, 26.8, 30.3 and 34.7kg/m2. S-factors (mGy/MBq.s) and SAFs (kg-1) were calculated for the dosimetry of the radiation from major source organs including spine, ribs, kidney and bladder into different target organs as well as whole body dosimetry from spine. The differences in dose estimates from different phantoms compared to those from the phantom with BMI of 26.8kg/m2 as the reference, were calculated for both gamma and beta radiations. The relative differences (RD) of the S-factors or SAFs from the values of reference phantom were calculated. RDs greater than 10% and 100% were frequent in radiations to organs for photon and beta particles, respectively. The relative differences in whole body SAFs from the reference phantom were 15.4%, 7%, 4.2%, -9.8% and -1.4% for BMIs of 18.6, 20.8, 22.1, 30.3 and 34.7kg/m2, respectively. The differences in whole body S-factors for the phantoms with BMIs of 18.6, 20.8, 22.1, 30.3 and 34.7kg/m2 were 39.5%, 19.4%, 8.8%, -7.9% and -4.3%, respectively. The dosimetry of the gamma photons and beta particles changes substantially with the use of phantoms with different BMIs. The change in S-factors is important for dose calculation and can change the prescribed therapeutic dose of 153Sm-EDTMP. Thus a phantom with BMI better matched to the patient is suggested for therapeutic purposes where dose estimates closer to those in the actual patient are required.

Palliative treatment of metastatic bone pain with radiopharmaceuticals: A perspective beyond Strontium-89 and Samarium-153.

PURPOSE: The present review article aims to provide an overview of the available radionuclides for palliative treatment of bone metastases beyond (89)Sr and (153)Sm. In addition, it aims to review and summarize the clinical outcomes associated with the palliative treatment of bone metastases using different radiopharmaceuticals. MATERIALS AND METHODS: A literature search was conducted on Science Direct and PubMed databases (1990 - 2015). The following search terms were combined in order to obtain relevant results: "bone", "metastases", "palliative", "care", "therapy", "treatment", "radiotherapy", "review", "radiopharmaceutical", "phosphorus-32", "strontium-89", "yttrium-90", "tin-117m", "samarium-153", "holmium-166", "thulium-170", "lutetium-177", "rhenium-186", "rhenium-188" and "radium-223". Studies were included if they provided information regarding the clinical outcomes. RESULTS AND CONCLUSIONS: A comparative analysis of the measured therapeutic response of different radiopharmaceuticals, based on previously published data, suggests that there is a lack of substantial differences in palliative efficacy among radiopharmaceuticals. However, when the comparative analysis adds factors such as patient's life expectancy, radionuclides' physical characteristics (e.g. tissue penetration range and half-life) and health economics to guide the rational selection of a radiopharmaceutical for palliative treatment of bone metastases, (177)Lu and (188)Re-labeled radiopharmaceuticals appear to be the most suitable radiopharmaceuticals for treatment of small and medium/large size bone lesions, respectively.

Neutron Activated Samarium-153 Microparticles for Transarterial Radioembolization of Liver Tumour with Post-Procedure Imaging Capabilities.

INTRODUCTION: Samarium-153 (153Sm) styrene divinylbenzene microparticles were developed as a surrogate for Yttrium-90 (90Y) microspheres in liver radioembolization therapy. Unlike the pure beta emitter 90Y, 153Sm possess both therapeutic beta and diagnostic gamma radiations, making it possible for post-procedure imaging following therapy. METHODS: The microparticles were prepared using commercially available cation exchange resin, Amberlite IR-120 H+ (620-830 µm), which were reduced to 20-40 µm via ball mill grinding and sieve separation. The microparticles were labelled with 152Sm via ion exchange process with 152SmCl3, prior to neutron activation to produce radioactive 153Sm through 152Sm(n,γ)153Sm reaction. Therapeutic activity of 3 GBq was referred based on the recommended activity used in 90Y-microspheres therapy. The samples were irradiated in 1.494 x 10(12) n.cm(-2).s(-1) neutron flux for 6 h to achieve the nominal activity of 3.1 GBq.g(-1). Physicochemical characterisation of the microparticles, gamma spectrometry, and in vitro radiolabelling studies were carried out to study the performance and stability of the microparticles. RESULTS: Fourier Transform Infrared (FTIR) spectroscopy of the Amberlite IR-120 resins showed unaffected functional groups, following size reduction of the beads. However, as shown by the electron microscope, the microparticles were irregular in shape. The radioactivity achieved after 6 h neutron activation was 3.104 ± 0.029 GBq. The specific activity per microparticle was 53.855 ± 0.503 Bq. Gamma spectrometry and elemental analysis showed no radioactive impurities in the samples. Radiolabelling efficiencies of 153Sm-Amberlite in distilled water and blood plasma over 48 h were excellent and higher than 95%. CONCLUSION: The laboratory work revealed that the 153Sm-Amberlite microparticles demonstrated superior characteristics for potential use in hepatic radioembolization.

Estimated human absorbed dose of a new (153)Sm bone seeking agent based on biodistribution data in mice: Comparison with (153)Sm-EDTMP.

PURPOSE: The main goal in radiotherapy is to deliver the absorbed dose within the target organs in highest possible amount, while the absorbed dose of the other organs, especially the critical organs, should be kept as low as possible. In this work, the absorbed dose to human organs for a new (153)Sm bone-seeking agent was investigated. METHODS: (153)Sm-(4-{[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl) acetic acid ((153)Sm-BPAMD) complex was successfully prepared. The biodistribution of the complex was investigated in male Syrian mice up to 48 h post injection. The human absorbed dose of the complex was estimated based on the biodistribution data of the mice by radiation absorbed dose assessment resource (RADAR) method. The target to non-target absorbed dose ratios for (153)Sm-BPAMD were compared with these ratios for (153)Sm-EDTMP. RESULTS: The highest absorbed dose for (153)Sm-BPAMD was observed in bone surface with 5.828 mGy/MBq. The dose ratios of the bone surface to the red marrow and to the total body for (153)Sm-BPAMD were 5.3 and 20.0, respectively, while these ratios for (153)Sm-EDTMP were 4.4 and 18.3, respectively. This means, for a given dose to the bone surface as the target organ, the red marrow (as the main critical organ) and the total body would receive lesser absorbed dose in the case of (153)Sm-BPAMD. CONCLUSIONS: Generally, the human absorbed dose estimation of (153)Sm-BPAMD indicated that all other tissues approximately received insignificant absorbed dose in comparison with bone surface and therefore can be regarded as a new potential agent for bone pain palliation therapy.

Samarium-153Sm-EDTMP as an equivalent variant to pharmaceutical analgesic treatment.

PURPOSE: Cancer pain is the most serious symptom for patients, especially during their terminal phase, when palliative medicine is needed. Our study tried to verify the usefulness of single-shot intravenous administration of Samarium (Sm)-153EDTMP in patients with bone metastases (group-A, N=53, males=25, females=28, age range: 30-69 years), as well as to compare a series of variables, using as a control group (group-B, N=37, males=17, females=20, age range: 30-69 years) with patients who were under drug treatment given from a physician specialized in palliative medicine. METHODS: Both groups answered the following questionnaires: Greek Brief Pain Inventory (GBPI), Brief Multidimensional Life Satisfaction Scale (BMLSS), Hospital Anxiety Depression Scale (HADS) and ECOG performance status. RESULTS: Pain severity and pain interference improvement p=0.0005 for both groups. HADS-anxiety: Samarium group, p= 0.397, drugs group p= 0.031. HADS-depression improvement for both groups p=0.031 and p=0.003, respectively. BMLSS improvement p=0.029 and p=0.265, while EGOG PS improvement was p=0.005 and p=0.014, respectively (numeric values). CONCLUSION: Intravenous administration of Sm-153EDTMP was equivalent to drug treatment against cancer pain for patients with multiple bone metastasis, an option for those patients who are intolerant or resistant to drug treatment. Samarium-treated patients needed less or not at all pain killers, having a better cost-effective result.

Comparative analysis of 11 different radioisotopes for palliative treatment of bone metastases by computational methods.

PURPOSE: Throughout the years, the palliative treatment of bone metastases using bone seeking radiotracers has been part of the therapeutic resources used in oncology, but the choice of which bone seeking agent to use is not consensual across sites and limited data are available comparing the characteristics of each radioisotope. Computational simulation is a simple and practical method to study and to compare a variety of radioisotopes for different medical applications, including the palliative treatment of bone metastases. This study aims to evaluate and compare 11 different radioisotopes currently in use or under research for the palliative treatment of bone metastases using computational methods. METHODS: Computational models were used to estimate the percentage of deoxyribonucleic acid (DNA) damage (fast Monte Carlo damage algorithm), the probability of correct DNA repair (Monte Carlo excision repair algorithm), and the radiation-induced cellular effects (virtual cell radiobiology algorithm) post-irradiation with selected particles emitted by phosphorus-32 ((32)P), strontium-89 ((89)Sr), yttrium-90 ((90)Y ), tin-117 ((117m)Sn), samarium-153 ((153)Sm), holmium-166 ((166)Ho), thulium-170 ((170)Tm), lutetium-177 ((177)Lu), rhenium-186 ((186)Re), rhenium-188 ((188)Re), and radium-223 ((223)Ra). RESULTS: (223)Ra alpha particles, (177)Lu beta minus particles, and (170)Tm beta minus particles induced the highest cell death of all investigated particles and radioisotopes. The cell survival fraction measured post-irradiation with beta minus particles emitted by (89)Sr and (153)Sm, two of the most frequently used radionuclides in the palliative treatment of bone metastases in clinical routine practice, was higher than (177)Lu beta minus particles and (223)Ra alpha particles. CONCLUSIONS: (223)Ra and (177)Lu hold the highest potential for palliative treatment of bone metastases of all radioisotopes compared in this study. Data reported here may prompt future in vitro and in vivo experiments comparing different radionuclides for palliative treatment of bone metastases, raise the need for the careful rethinking of the current widespread clinical use of (89)Sr and (153)Sm, and perhaps strengthen the use of (223)Ra and (177)Lu in the palliative treatment of bone metastases.

Comparison of the effect of knee synovectomy in haemophilic patients with 153Sm- and 90Y-labelled hydroxyapatite 1 year after.

To compare the use of 740 Mbq (20 mCi) of (153) Sm and 185 Mbq (5mCi) of (90) Y, both labelling hydroxyapatite (HA), for knee synovectomy in haemophilic patients, 1 year after the intervention. Thirty three men (36 knees) were studied, divided into two groups: 1 - treatment using 740 Mbq of (153) Sm-HA: 20 knees of 18 patients, with mean age of 21.4 ± 13.3 years (ranging from 7 to 56 years) and mean Pettersson score of 5.3; 2 - treatment using 185 Mbq of (90) Y-HA: 16 knees of 15 patients, with mean age of 26.3 ± 10.3 (ranging from 7 to 51 years) and mean Pettersson score of 6.3. The following criteria were adopted for the evaluation before and 1 year after synovectomy: reduction in haemarthrosis episodes and pain using a visual analogue scale, as well as improved joint mobility. The occurrence of adverse events in the treatment was also considered. The chi-square, Wilcoxon and Mann-Whitney tests were used with P ≤ 0.05 set as significant. The occurrence of haemarthrosis declined by 65.7% with the use of (153) Sm-HA and 82.6% for (90) Y-HA, with no statistical difference between the groups (P = 0.632); pain reduction was 42.5% in group 1 and 30.7% in group 2, once again with no statistical difference (P = 0.637). Improvement in joint mobility was not significant for both groups. Two cases of mild reactive synovitis were observed in group 1 and one in group 2, which cleared up without medical intervention. Although the beta energy from (90) Y is the gold standard for knee synovectomy, higher activities of (153) Sm may be used in places which have only production of this material.

Palliative treatment of bone metastases with samarium-153 EDTMP at onset of pain.

We evaluated the pain response and daily discomfort in patients suffering from a borderline degree of bone pain due to breast or lung cancer bone metastases, who had undergone early palliative radionuclide treatment. The results were compared with those from patients who had received standard analgesic therapy. Twenty-one patients (65.7 ± 3 years; 17 women) with metastatic bone cancer underwent samarium-153 (Sm-153) ethylene diamine tetramethylene phosphonate (EDTMP) administration (group A) and 18 patients (64.3 ± 8 years; 16 women)continued to receive standard analgesics (group B; control group). The patients kept a daily pain diary assessing both their discomfort and the pain at specific sites by means of a visual analog scale, rating from 0 (no discomfort­no pain)to 10 (worst discomfort­pain). These diaries were reviewed weekly for 2 months and three physicians rated the pain response on a scale from -2 (considerable deterioration) to +2 (considerable improvement). Baseline characteristics were similar in both groups. The reduction of total discomfort and of bone pain in group A was significantly greater compared to group B (p < 0.0001). A significant improvement of clinical conditions was observed in group A, where the physician rate changed from -1 to 1, compared to group B in which the rate changed from -1 to 0. Sm-153 EDTMP therapy can be considered for patients with bone pain from breast and lung cancer in advance, i.e.,before the establishment of severe pain syndrome.

Radioactive synovectomy with (90) yttrium and (153) samarium hydroxyapatite in haemophilic joints: preliminary study on radiation safety.

Most countries still do not achieve 1 IU of factor VIII/capita sufficient for survival. Although primary prophylaxis prevents synovitis, is not universally used. Chronic synovitis is treated with arthroscopy at expense of considerable amount of coagulation factors, and specialized surgeons. Radioactive synovectomy (RS) is a minimally invasive and cost effective alternative to arthroscopy, often considered first the option for persistent synovitis. Even without established causation with cancer, RS is avoided by some, due to this concern. We aim contributing to the understanding of RS safety regarding malignancy, presenting a large number of treated patients, and a single case of cancer. Three centres in Brazil applied RS with (90) Yttrium Citrate, (90) Yttrium hydroxyapatite or (153) Samarium hydroxyapatite in haemophilic joints and performed a survey addressing cancer in these patients. Four hundred and eighty eight patients (ages 3-51) received 1-3 RS (total 842) and follow-up was 6 months to 9 years. One patient aged 14 years presented Ewing sarcoma, 11 months after RS. The tumour was treated successfully with surgery and chemotherapy. Causality of cancer by RS is improbable in this case. Accordingly, latency here is far below minimum 5-10 years for radio-induction of solid tumours. Moreover, ES is not a typically radio-induced tumour, even at high doses. In agreement with others, though recognizing limitations, this study suggests RS is safe regarding cancer induction. Synovitis is a known burden for patients. The decision of making reasonable usage of RS should be outweighed with the risks of leaving synovitis untreated.

A prospective randomized trial: a comparison of the analgesic effect and toxicity of 153Sm radioisotope treatment in monotherapy and combined therapy including local external beam radiotherapy (EBRT) among metastatic castrate resistance prostate cancer (mCRPC) patients with painful bone metastases.

Bone metastases in prostate cancer constitute the most frequent cause of systemic failure in treatment, which results in numerous complications and finally leads to patient's death. Pain is one of the first and most important clinical symptoms of bone metastases and can be found among more than 80% of patients. Therefore, the most analgetic effective and simultaneously the least toxic treatment is an important point of therapeutic management in this group of patients. The aim of this prospective clinical trial was a comparison of analgetic effectiveness and toxicity of monotherapy with 153Sm isotope to combined therapy (153Sm + EBRT) among patients diagnosed with multiple painful bone metastases due to CRPC (mCRPC). 177 patients with mCRPC were included into the prospective randomised clinical trial in which 89 patients were assigned to the 153Sm isotope monotherapy, while 88 patients were assigned to the combined therapy including 153Sm isotope therapy and EBRT. All patients were diagnosed (bone scan and X-ray or/and CT or/and MRI) with painful bone metastases (bone pain intensity >= 6 according to VAS classification). The following additional inclusion criteria were established: histologically confirmed adenocarcinoma of prostate, multifocal bone metastases, no prior chemotherapy or palliative radiotherapy to bone. All patients signed informed consent.The combination of the isotope therapy with EBRT was more effective analgetic treatment than isotope therapy alone. The highest pain decline was noticed in the first weeks after treatment termination. In the whole group, a total or partial analgesic effect was observed among 154 (87%) patients while among 23 (13%) patients there was a lack of analgesic effect or even pain intensification. The results of this clinical trial demonstrated that for patients with multiple mCRPC it is recommended to combine the 153Sm isotope therapy with local EBRT because of a greater analgetic effect. It is important to note that combined therapy did not intensify the toxicity of treatment.