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PubMed2002

Samarium-153-EDTMP bone uptake rate and its relation to therapeutic effect.

OBJECTIVE: To evaluate the measurement of Samarium-153 ethylenediaminetetramethylene phosphonic acid ((153)Sm-EDTMP) bone uptake rate using whole-body scintigraphy and analyze the relationship between bone uptake rate and therapeutic effect. METHODS: Sixty-six patients with painful bony metastases from prostate (n = 15), lung (n = 20), breast (n= 18), nasopharyngeal carcinoma (NPC) (n=5), colon (n=2), kidney (n=2) and unknown cause (n=4) carcinoma were examined with whole-body scintigraphy 10 min and 5 h post administration of (153)Sm-EDTMP. Bone uptake rate was then calculated. (1 ) Complete response (CR): disappearance of > 2 metastases, Karnofsky Performance Score (KPS) increase > 20, moderate or complete remission of bone pain 7 d post injection of (153)Sm-EDTMP. (2) Partial response (PR): disappearance of 1-2 metastases, KPS increase 10-20, moderate remission of bone pain in 3 wk. (3) Non-response (NR): no disappearance or shrinkage of metastases, KPS increase < 10, no or slight remission of bone pain. RESULTS: The range of bone uptake rate in 66 patients was 31 .9% - 86.6% (mean = 56. 0%). The bone uptake rate in the CR group (17 cases, 25.7%), PR group (24 cases, 36.4%), and NR group (25 cases, 37.9%) was 52.4% - 86.6% (mean = 68.7%), 43.7% - 70.4% (mean = 58.3%), and 31.9%- 51 .5% (mean = 41 . 0%) respectively. Statistical analysis showed that there was a significant difference between the CR and PR groups ( t = 4.258, P = 0.001 ) as well as between PR and NR groups ( t = 8.48,P = 0.001 ). CONCLUSIONS: Using a simple and reliable whole-body scintigraphic technique to calculate prospectively the bone uptake rate, we have, for the first time in China, reported the relationship between bone uptake rate and therapeutic effect. This allows nuclear medicine physicians to calculate a safe and effective dose of (153)Sm-EDTMPin individual patients to palliate bone cancer pain without myelotoxicity.

Bone Neoplasms↗
PubMed1992

Samarium-153-EDTMP: pharmacokinetic, toxicity and pain response using an escalating dose schedule in treatment of metastatic bone cancer.

Samarium-153 emits medium-energy beta particles and an imageable gamma photon with a physical half-life of 46.3 hr. When chelated to ethylenediaminetetramethylenephosphonic acid (EDTMP), it is remarkably stable in vitro and in vivo. In this study, we administered escalating amounts of 153Sm-EDTMP, from 0.1 to 1.0 mCi/kg (3.7-37 MBq/kg), to 22 patients with painful metastatic bone cancer. A complete concordance was found when the scintigrams of 153Sm-EDTMP were compared qualitatively to 99mTc-HDP bone images. Moreover, the skeletal uptake of the 153Sm-EDTMP related to the number of metastatic sites (r = 0.65; p = 0.001) showed an inverse proportion to the plasma radioactivity at 30 min following injection (r = -0.79; p = 0.0001) and was unaffected by the administered (mCi/kg), (r = 0.33; p = 0.13). Myelotoxicity was observed in 10 of the 29 treatment courses and leukopenia occurred in two. Thrombocytopenia occurred in patients who had low pretreatment platelet counts, albeit within the normal range (p = 0.001), most suffered from prostate cancer (p = 0.007) and retained a higher percentage of the 153Sm-EDTMP in their skeleton (p = 0.057). In four patients an exacerbation of the pre-existing pain ("flare reaction") was recorded. Pain palliation occurred in 65% of the treated patients (mean: 3.8 mo, range: 1-11 mo). Retreatment in first time responder patients was quite effective. Our preliminary results indicate that 153Sm-EDTMP is a promising radiotherapeutic agent for palliative treatment of metastatic bone cancer pain, and further study is necessary to ascertain its optimal dose, efficacy and toxicity.

Adult↗
PubMed2000

Systemic radionuclide therapy with Samarium-153-EDTMP for painful bone metastases.

METHODS: We introduced in 33 patients intravenous systemic administration of Samarium-153-EDTMP. Average age of patients was 61 years, range from 29 to 83 years. Mean application activity was 39 MBq per kg of patient's body weight. RESULTS: One month after this administration we observed a significant analgetic effect in 37% of patients, partial analgetic effect in 37% and we noticed no effect in 26% of patients. Three months after administration we observed a significant analgetic effect in 45% of patients, a partial effect in 26% and no effect in 29% of patients. The withdrawal of bone pain was joined with an improvement of the patient's mobility and with the decrease of the necessary dose of anodynes and nonsteroid analgetics.

Journal Article↗
PubMed1998

[Determination of non-rare earth impurities including Cu, Fe, Ca and Ni in samarium oxide by ICP-AES].

The direct determination of non-rare earth trace impurities including Cu, Fe, Ca and Ni in high purity Samarium oxide by means of ICP-AES is presented in this paper. By using orthogonality experimentation, we studied main factors of influential determination and selected compromise condition of simultaneous determination of Cu, Fe, Ca and Ni. Influence of matrix concentration was discussed. We used the method of matrix match and subtraction background. For the sample solution containing 5mg/mL of Sm2O3 the determination limits were 0. 0003% for Cu, 0.003% for Ni, 0.001% for Ca and Fe, respectively. The relative standard deviation was in the range of 2.6-9.2%. The recovery ratio of these elements was in the range of 90-110%. The method is simple and rapid. It was fit to productive control analysis and determination of production.

English Abstract↗
PubMed1997

[Study on atomic emission spectrum and spectral interferences of rare earth elements with a high resolution inductively coupled plasma atomic emission spectrometer.--II. Spectral intererences of Samarium matrix].

The rare earth elements play a very important role in today's manufacture and life. For their complex spectra it is difficult to determine the trace elements in rare earth element matrix. This work investigated the spectral interferences of samarium matrix on other rare earth elements with a high resolution inductively coupled plasma atomic emission spectrometer. A lots of spectrum information and spectral interferences were obtained, which are quite useful in the selection of analytical lines that free of spectral interferences and the elimination of the concomitant's interferences.

English Abstract↗
PubMed2003

Mass spectrometric studies of cyclopentanol derivatives in the reductive coupling of alpha,beta-unsaturated ketones assisted by samarium diiodide.

The mass spectrometric fragmentations of a series of cyclopentanol derivatives in positive fast-atom bombardment (FAB(+)) mode were investigated. The corresponding pathways proposed were confirmed by MS/MS data obtained using linked scans at constant B/E, high-resolution accurate mass data, and comparisons with corresponding information for a specifically deuterated molecule.

Cyclopentanes↗
PubMed1989

Samarium-153 EDTMP therapy of disseminated skeletal metastasis.

153Sm-EDTMP (ethylenediaminetetramethylene phosphonate), prepared from a kit, was administered to 28 patients in a clinical trial of therapy for painful skeletal metastases unresponsive to all conventional treatment. The 103 keV gamma emission of 153Sm was utilized for prospective individual estimation of beta radiation absorbed dose to red marrow to minimize myelotoxicity and provide optimum internal radiotherapy to skeletal metastases in each patient. Pain relief occurred within 14 days of administration of 153Sm-EDTMP in 15 of 19 patients (79%) who could be evaluated at 6 weeks, when clinical response was maximal. Duration of response ranged from 4 to 35 weeks. Recurrence of pain responded to retreatment with 153Sm-EDTMP in five of eight cases. No dose-response relationship was apparent for pain relief but reversible myelotoxicity was frequently observed at radiation absorbed doses to bone marrow greater than or equal to 270 cGy. Dosimetry calculation was based on pharmacokinetic studies of a tracer administration of 153Sm-EDTMP in each patient. Assumptions inherent in this prospective method of predicting dose to bone marrow were validated experimentally. Biodistribution studies in rats demonstrated rapid skeletal uptake and long term retention of 153Sm-EDTMP in bone over 5 days. Urinary clearance accounted for 40% of injected dose, and less than 1.0% of administered activity was retained in non osseous tissue. Microdensitometry of autoradiographs of sheep vertebra and femur confirmed surface uptake of 153Sm-EDTMP in cortical bone and demonstrated relatively high trabecular bone activity which is the major component of radiation absorbed dose to bone marrow. Haematological studies in rabbits showed 153Sm-EDTMP-induced myelotoxicity to be transient and no histopathological abnormalities were demonstrable with doses ten times greater than those administered to patients.

Animals↗
PubMed1987

Samarium-153 chelate localization in malignant melanoma.

153Sm, a radiolanthanide of half life 46.27 h, has a gamma emission of 0.103 MeV which is well suited to imaging, it is also a moderate energy beta emitter and tumour localization of various 153Sm chelates was evaluated in B16 murine melanoma to assess their endoradiotherapeutic potential. 153Sm was prepared from enriched 152Sm in the Australian Nuclear Science and Technology Organization reactor. 153Sm chelates were prepared from 153Sm-chloride and their chromatographic behaviour characterized. Tumour and organ uptake of 153Sm-chloride, 153Sm-citrate and the 153Sm chelates, DTPA, HEDTA, HIDA, BZ, PBH, PIH and NTA were measured at 1, 6, 24 and 48 h after intravenous administration to C57 black mice bearing either melanotic or amelanotic B16 melanoma of mean size 0.75 cm3. Histopathological examination of the tumours at each passaging assured comparability of the degree of melanogenesis and the absence of necrosis. 153Sm-chloride was immobile on chromatography and the rapid hepatic accumulation of both 153Sm-chloride and 153Sm-citrate was attributed to in vivo formation of a colloid. In contrast, 153Sm-DTPA, moving at the solvent front on chromatography, showed no reticuloendothelial accumulation in vivo and was rapidly excreted by the kidneys without tumour uptake. The other 153Sm chelates were of intermediate stability and all localized in both melanotic and amelanotic tumours, although to a significantly lesser degree than 67Ga-citrate. The relatively high 153Sm-HIDA activity in liver and 153Sm-NTA activity in bone impaired tumour definition, but on imaging of all the 153Sm chelates only 153Sm-DTPA failed to demonstrate the B16 melanoma and the best tumour delineation was obtained using 153Sm-HEDTA.

Animals↗
PubMed1984

Sectional prostheses connected by samarium-cobalt magnets.

Large acquired defects with undercuts can be restored with sectional prostheses. Sections of the prosthesis can be connected with small Sm-Co magnet pairs. The advantages of Sm-Co magnets are that (1) sections of prostheses can be connected by magnets less than 1 cm in size, (2) they can be embedded in thin sections of acrylic resin, (3) they are easy to place, (4) insertion is easy (magnetic attraction enhances), (5) hollow obturators can be used, and (6) tissue undercuts can be used for additional retention of prostheses.

Cobalt↗
PubMed2005

Highly functionalised cyclobutanols via samarium(II) iodide-induced pinacol cyclisations of carbohydrate-derived 1,4-diketones.

D-Ribofuranose and D-arabinofuranose derivatives were converted in a few steps into their 1,4-diketone derivatives, which were pinacol cyclised under the action of SmI2 to form the corresponding chiral cyclobutanediol products. These products can potentially be applied to the synthesis of anti-viral agents, some of whose structures incorporate chiral cyclobutanediol moieties.

Antiviral Agents↗
PubMed2004

Influence of trans-1,2-diaminocyclohexane structure and mixed carboxylic/phosphonic group combinations on samarium-153 chelation capacity and stability.

A simple procedure was developed to compare chelating agents for (153)Sm complexes as a preliminary step to synthesise bifunctional analogues. Several variables affecting the efficiency of complex stability were investigated, such as the pre-organisation concept, cavity size, and the nature of coordination sites. Four semi-rigid agents incorporating carboxylic and/or phosphonic groupings fixed at trans-1,2-diaminocyclohexane were evaluated for their (153)Sm chelation properties, and competition studies were performed. Data on the stability of the best chelating agent compound 3: trans-cyclohexane-1,2-bis(aminomethylphosphonic)-N,N'-bis(ethyl-2-iminodiacetic acid) in human serum are presented.

Carboxylic Acids↗
PubMed2006

Fluorimetric determinations of nucleic acids using iron, osmium and samarium complexes of 4,7-diphenyl-1,10-phenanthroline.

New sensitive, reliable and reproducible fluorimetric methods for determining microgram amounts of nucleic acids based on their reactions with Fe(II), Os(III) or Sm(III) complexes of 4,7-diphenyl-1,10-phenanthroline are proposed. Two complementary single stranded synthetic DNA sequences based on calf thymus as well as their hybridized double stranded were used. Nucleic acids were found to react instantaneously at room temperature in Tris-Cl buffer pH 7, with the investigated complexes resulting in decreasing their fluorescence emission. Two fluorescence peaks around 388 and 567 nm were obtained for the three complexes using excitation lambda(max) of 280 nm and were used for this investigation. Linear calibration graphs in the range 1-6 microg/ml were obtained. Detection limits of 0.35-0.98 microg/ml were obtained. Using the calibration graphs for the synthetic dsDNA, relative standard deviations of 2.0-5.0% were obtained for analyzing DNA in the extraction products from calf thymus and human blood. Corresponding Recovery% of 80-114 were obtained. Student's t-values at 95% confidence level showed insignificant difference between the real and measured values. Results obtained by these methods were compared with the ethidium bromide method using the F-test and satisfactory results were obtained. The association constants and number of binding sites of synthetic ssDNA and dsDNA with the three complexes were estimated using Rosenthanl graphic method. The interaction mechanism was discussed and an intercalation mechanism was suggested for the binding reaction between nucleic acids and the three complexes.

Animals↗
PubMed2000

Studies on the preparation and stability of samarium-153 propylene diamine tetramethylene phosphonate (PDTMP) complex as a bone seeker.

Propylene diamine tetra methylene phosphonate (PDTMP) was synthesised by modifying a method reported for the synthesis of EDTMP. Complexation of the synthesised phosphonate ligand with 153Sm was carried out by varying the experimental parameters and the complex was radiochemically characterized. Biodistribution studies showed that the uptake by bone in rats was 2% per g of bone, which was retained upto 48 h. The uptake by other organs was insignificant, except by the liver which showed a slightly higher absorption.

Animals↗