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In this study, the radiocomplexation of risedronic acid, a potent bisphosphonate with a no carrier added (NCA) 177Lu, was investigated and followed by quality control studies, biodistribution evaluation, and dosimetry study for human based on biodistribution data in Wistar rats. The moderate energy β− emitter, 177Lu ( T½ = 6.7 days, Eβmax = 497 keV), has been considered as a potential agent for development of bone-seeking radiopharmaceuticals. Because the specific activity of the radiolabeled carrier molecules should be high, the NCA radionuclides have an effective role in nuclear medicine. Many researchers illustrated an NCA 177Lu production; among these separation techniques, extraction chromatography has been considered more capable than other methods. The NCA 177Lu was produced with specific activity of 48 Ci/mg and radionuclidic purity of 99.99% by the irradiation of enriched 176Yb target in thermal neutron flux of 4 × 1013 n·cm−2·s−1 for 14 days. The NCA 177Lu was mixed to a desired amount of sodium risedronate (15 mg/mL, 200 μL) and incubated with stirring at 95°C for 30 minutes. The radiochemical purity of 177Lu-risedronate was determined by radio thin-layer chromatography, and high radiochemical purities (>97%) were obtained under optimized reaction conditions . The complex was injected to Wistar rats, and complex biodistribution was performed 4 hours to 7 days postinjections showing high bone uptake (9.8% ± 0.24% ID/g at 48 hours postinjection). Also, modeling the radiation dose delivery by RADAR software for the absorbed dose evaluation of each human organ showed a major accumulation of the radiocomplex in bone tissue. [ABSTRACT FROM AUTHOR]

Aim: Various phosphonate ligands labeled with β--emitting radionuclides have shown good efficacy for bone pain palliation. In this study, a new agent for bone pain palliation has been developed.Materials and Methods: Samarium-153-(4-[((bis(phosphonomethyl))carbamoyl)methyl]-7,10-bis (carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl) acetic acid (153Sm-BPAMD) complex was prepared using BPAMD ligand and samarium-153 chloride. The effect of various parameters on the labeling yield of 153Sm-BPAMD including ligand concentration, pH, temperature, and reaction time were studied. Production of 153Sm was performed at a research reactor using 152Sm (n, γ)153Sm nuclear reaction. The radiochemical purity of the radiolabeled complex was checked by instant thin layer chromatography. Stability studies of the complex in the final preparation and the presence of human serum were performed up to 48 h. Partition coefficient and hydroxyapatite (HA) binding of the complex were investigated and biodistribution studies using single photon emission computed tomography (SPECT) and scarification were performed after injection of the complex to wild-type mice.Results: 153Sm-BPAMD was prepared in a high radiochemical purity >98% and specific activity of 267 GBq/mmol at the optimal conditions. The complex demonstrated significant stability at the room temperature and in human serum at least for 48 h. HA binding assay demonstrated that at the amount of more than 5 mg, approximately, all radiolabeled complex was bind to HA. At the pH 7.4, log Po/w was - 1.86 ± 0.02. Both SPECT and scarification showed major accumulation of the labeled compound in the bone tissue.Conclusions: The results show that 153Sm-BPAMD has interesting characteristics as an agent for bone pain palliation, however, further biological studies in other mammals are still needed. [ABSTRACT FROM AUTHOR]

Objective: Various phosphonate ligands labeled with β(-)-emitting radionuclides have shown good efficacy for bone pain palliation. In this study, a new agent for bone pain palliation has been developed.Methods: ¹⁵³Sm-(4-{[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl) acetic acid (¹⁵³Sm-BPAMD) complex was prepared using BPAMD ligand and ¹⁵³SmCl3. The effect of various parameters on the labeling yield of ¹⁵³Sm-BPAMD including ligand concentration, pH, temperature and reaction time were studied. Radiochemical purity of the radiolabeled complex was checked by instant thin layer chromatography (ITLC). Stability studies of the complex in the final preparation and in the presence of human serum were performed up to 48 h. Partition coefficient and hydroxyapatite (HA) binding of the complex were investigated and biodistribution studies (SPECT imaging and scarification) were performed after injection of the complex to Syrian mice up to 48 h post-injection. The biodistribution of the complex was compared with the biodistribution of the ¹⁵³Sm cation in the same type mice.Results: ¹⁵³Sm-BPAMD was prepared in high radiochemical purity >98% and specific activity of 267 GBq/mmol at the optimal conditions. The complex demonstrated significant stability at room temperature and in human serum at least for 48 h. HA binding assay demonstrated that at the amount of more than 5 mg, approximately, all radiolabeled complex was bound to HA. At the pH 7.4, LogP o/w was -1.86 ± 0.02. Both SPECT and scarification showed major accumulation of the labeled compound in the bone tissue.Conclusion: The results show that ¹⁵³Sm-BPAMD has interesting characteristics as an agent for bone pain palliation; however, further biological studies in other mammals are still needed. [ABSTRACT FROM AUTHOR]

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Particle emitter 1,4,7,10-tetraazacyclododecane-1,4,7,10 tetraethylene phosphonic acid complexes (DOTMP) are used for delivering high doses to bone marrow as well as palliative therapy. In this research production, quality control and biodistribution studies of [In]-DOTMP with respect to its radiochemical and in vivo biological characteristics have been presented for imaging as well as dosimetry studies of therapeutic analogs. [In]-DOTMP complex was obtained in high radiochemical purity (>99 %, ITLC) under at optimized conditions. This complex exhibited excellent in vitro stability at room temperature and human serum. Biodistribution studies in rats showed favorable selective skeletal uptake with rapid clearance from blood along with insignificant accumulation of activity in other non-target organs using tissue dissection and single-photon emission computed tomography (SPECT). This tracer can be used in the long term skeletal studies in SPECT procedures as well as presenting a dosimetry probe for therapeutic DOTMP analogs. [ABSTRACT FROM AUTHOR]

177Lu-ethylenediaminetetramethylene phosphonic acid (EDTMP) is presently suggested as an excellent bone seeking radionuclide for developing metastatic bone pain (MBP) palliation agent owing to its suitable nuclear decay characteristics. To find the exact dosage and its efficiency, this clinical study was performed on the human being, using 177Lu-EDTMP for MBP palliation. 177Lu-EDTMP was prepared by Iran, atomic energy organization. Thirty consecutive patients with determined tumors, incontrollable MBP, and positive bone scan at 4 weeks before the beginning of the study participated in this study in the nuclear medicine ward. 177Lu-EDTMP in the form of sterile slow IV injection was administered with a dose of 29.6 MBq/kg. Short form of brief pain inventory questionnaire was used to evaluate the efficiency of the intervention. Questionnaires were filled out by an expert nuclear physician every 2 weeks while the cell blood count was also checked every 2 weeks up to 12 weeks for evaluation of bone marrow suppression and hematological toxicity. Furthermore, whole body scan was done at days 1, 3, and 7. Twenty-five patients showed a significant pain relief since 2 weeks after the injection, and continued until the end of the follow up period (12 weeks). There were no significant early complications such as bone marrow suppression, hematological toxicity, and no systemic adverse effects. No complication was observed in renal function. Twenty one patients showed flare phenomenon that was started after the 12.2 ± 1.78 h lasting for 38.4 ± 23.08. Sixteen patients (53%) were completely treated; nine patients (30%) showed a partial response, and five patients (17%) had no response to treatment. Total response to treatment was achieved in 25 patients (83%). At the end of the evaluation, no bone marrow suppression or hematologic toxicity was observed. 177Lu-EDTMP has shown suitable physical and biological properties with good results in long term bone pain relief for patients with bone metastasis. [ABSTRACT FROM AUTHOR]

In this work, the cocktail complex Sm/Lu-EDTMP was prepared in high radiochemical purity (more than 99 %) using in house synthesized EDTMP ligand for obtaining a possible synergistic wide range palliative agent. The mixture was administered to wild-type rats and biodistribution data collected after 2 h to 7 days showed at least 70 % accumulation of the radioactivity in the bone tissues. Scintigraphic images were taken from wild-type rats injected with Sm/Lu-EDTMP after 24 h and the biodistribution was shown to be consistent with post-mortem data. A comparative accumulation study was performed for vital organs up to 7 days. Sm/Lu-EDTMP seemed a promising agent for bone pain palliation therapy in skeletal metastases in humans as a novel combined radiopharmaceutical. [ABSTRACT FROM AUTHOR]

Developing new bone pain palliation agents are a mandate in handling end-stage cancer patient's around the world. Lu (1-hydroxy-2-imidazol-1-yl-phosphonoethyl)phosphonic acid (Lu-ZLD) is a possible therapeutic agent which can be used in bone palliation therapy. In this study, Lu-ZLD complex was prepared successfully using commercial ZLD ligand and LuCl at 25 and 60 °C at various ligand:metal ratios for 60-360 min. Lu chloride was obtained by thermal neutron irradiation (4 × 10 n cms) of natural LuO samples. Radiochemical purity of Lu-ZLD was checked by ITLC and HPLC. Stability studies of final preparation in the presence of human serum were performed as well as protein binding studies and hydroxyapatite (HA) binding test. The biodistribution of Lu-ZLD and LuCl in mice were determined for 7 days. A comparative accumulation study for Lu-ZLD and Lu-EDTMP was performed for vital organs up to 7 days. The complex was obtained in high radiochemical purity ITLC (>97 %) and HPLC (>99.9 %) and satisfactory stability in presence of human serum and final formulations were obtained (≈90 % in 48 h). HA binding assay demonstrated >95 % binding from 5 to 20 mg of HA in 24 h at room temperature. The complex protein binding was about 55-58 %. The high bone uptake ratios at all time intervals was obtained (>9 % at day 7), bone:kidney and bone:liver uptake ratios were significantly high for ZLD at 7 day post injection but not superior to Lu-EDTMP. Due to longer physical half life of Lu compared to Sm and comparable ratios for Lu-ZLD compared to Lu-EDTMP, Lu-ZLD can be an interesting new candidate for clinical trials for bone pain palliation therapy. [ABSTRACT FROM AUTHOR]

In this study, the 166Ho-triethylene tetramine hexa (methylene phosphonic acid) (166Ho-TTHMP) complex was prepared as a bone palliation agent. The complex was successfully prepared using an in-house synthesized TTHMP ligand and [166Ho]HoCl3. Ho-166 chloride was obtained by thermal neutron irradiation (1×1013 n cm−2 s−1) of natural Ho(NO3)3 samples, followed by radiolabeling and stability studies. Biodistribution studies were also performed in wild type rats. The complex was prepared with the specific activity of 3-5 GBq/mg and a high radiochemical purity > 99%, (checked by ITLC). The 166Ho-TTHMP complex was stable in the final preparation and in the presence of human serum (> 90%) up to 72 h. The biodistribution of 166Ho-TTHMP in wild-type rats demonstrated significant bone uptake compared to 166HoCl3 up to 48 h. SPECT imaging of the radiolabeled compound was demonstrated to be in complete accordance with the biodistribution data. The major uptake was observed for long bones including thigh bones as well as skull and also knee and vertebrae. Primary properties of 166Ho-TTHMP demonstrate that this new therapeutic agent can be a good choice for metastatic bone pains. [ABSTRACT FROM AUTHOR]

Objective(s): In this work a new possible agent for radiosynovectomy has been targeted for articular pain palliation. Materials and Methods: Lu-177 of 2.6-3 GBq/mg specific activity was obtained by irradiation of natural Lu2O3 sample with thermal neutron flux of 4 × 1013 n.cm-2.s-1. The product was converted into chloride form which was further used for labeling of 177Lu-phytate complex and checked using ITLC (MeOH: H2O: acetic acid, 4: 4: 2, as mobile phase). The complex stability and viscosity were checked in the final solution up to seven days. The prepared complex solution (100 μCi/100 μl) was injected intra-articularly to male rat knee joint. Leakage of radioactivity from injection site and its distribution in organs were investigated up to seven days. Results: The complex was successfully prepared with high radiochemical purity (>99.9 %). Approximately, the whole injected dose has remained in injection site seven days after injection. Conclusion: The complex was proved to be a feasible agent for cavital radiotherapy in oncology and rheumatology. [ABSTRACT FROM AUTHOR]

Objective(s): In this study, 166Ho-1,2-propylene di-amino tetra(methy1enephosphonicAcid) (166Ho-PDTMP) complex was prepared as a bone palliation agent. Materials and Methods: The complex was successfully prepared using an in-house synthesized EDTMP ligand and 166HoCl3. Ho-166 chloride was obtained by thermal neutron irradiation (1 × 1013 n.cm-2.s-1) of natural Ho(NO3)3 samples followed by radiolabeling and stability studies. Biodistribution in wild type rats was also peformed. Results: The complex was prepared with the specific activity of 278 GBq/mg and high radiochemical purity (>99%, checked by ITLC). 166Ho-PDTMP complex was stabilized in the final preparation and in the presence of human serum (>90%) up to 72 hr. The biodistribution of 166Ho-PDTMP in wild-type rats demonstrated significant bone uptake was up to 48 hr compared to 166HoCl3. Conclusion: The produced 166Ho-PDTMP properties suggest a possible new bone palliative therapeutic to overcome the metastatic bone pains. [ABSTRACT FROM AUTHOR]

Developing new bone pain palliation agents is a mandate in handling end-stage cancer patients around the world. Possibly, Lu-177 ethylenediaminetetramethylene phosphonic acid (177Lu-EDTMP) is a therapeutic agent which can be widely used in bone palliation therapy. In this study, 177Lu-EDTMP complex was prepared successfully using synthesized EDTMP ligand and 177LuCl3. Lu-177 chloride was obtained by thermal neutron irradiation (4 x 1013 n.cm-2s-1) of natural Lu2O3 samples. Radiochemical purity of 177Lu-EDTMP was determined by ITLC (more than 99%). Stability studies of the final preparations in the presence of human serum were performed. The biodistribution of 177Lu-EDTMP and 177LuCl3 in wild-type rats was studied by SPECT imaging. A comparative accumulation study for 177Lu-EDTMP and 177LuCl3 was performed for vital organs up to 7 days. The complex was obtained in high radiochemical purity (more than 99%). The complex was stable in vitro in presence of human serum as well as final formulation. Significant bone uptake (> 70%) was observed for the radiopharmaceutical. Due to better physical properties of Lu-177 compared to Sm-153 and acceptable biodistribution results of the compound, 177Lu-EDTMP seemed to be an interesting new candidate for clinical trials for bone pain palliation therapy. [ABSTRACT FROM AUTHOR]

Introduction: Various bone palliative therapeutic agents have been developed and widely used for bone metastasis such as 153Sm-EDTMP. In this study, production, quality control and biodistribution studies of a newly developed therapeutic compound have been presented followed by imaging studies in wild-type rodents. Methods: 153Sm-TTHMP was prepared starting from 153Sm-SmCl3, prepared by neutron activation of an enriched 152Sm sample (purity >98%), and in-house synthesized TTHMP in 1h at 25°C followed by stability tests, partition coefficient determination and biodistribution studies of in wild-type rodents using scarification and SPECT imaging. Results: The radiolabled Sm complex was prepared in high radiochemical purity (>99%, ITLC) and specific activity of 278 GBq/mmol and demonstrated significant stability at 4, 25 and 37°C (in presence of human serum). Initial biodistribution data showed significant bone accumulation of the tracer in 48h. Conclusion: 153Sm-TTHMP can be a potential candidate for bone pain palliation therapy in skeletal metastases, although further biological studies in other mammals is still needed. [ABSTRACT FROM AUTHOR]

Background: Production of effective, low-cost, and efficient radiopharmaceuticals is an important task and requires further research and clinical studies. In this clinical trial, safety and efficacy of 177Lu/153Sm-ethylenediamine tetramethylene phosphonic acid (EDTMP) cocktail has been evaluated for pain relief of bone metastases. Materials and Methods: Twenty-five patients with the mean age of 55.5 ± 15.8 years participated in this study. Patients received a total dose of 37 MBq/kg. Pain and performance assessments were followed using a Brief Pain Inventory form. Complete blood count and renal and liver function tests were also performed up to 12 weeks postadministration. Results: Eighteen patients (72%) demonstrated complete pain relief (relief = 100%) and approximately all patients (96%) experienced significant improvement in their quality of life. No grade IV hematological toxicity was observed during the 12-week follow-up period, and grade III toxicity was seen in 1 patient only. In addition, no abnormalities were seen in renal and liver function during the follow-up period. Conclusions: There were no considerable complications after administration of 177Lu/153Sm EDTMP; this cocktail seems to be a safe and effective treatment for bone pain palliation in patients with skeletal metastases and improves the quality of life. [ABSTRACT FROM AUTHOR]