Development of 186/188Re-Chitosan as an Effective Therapeutic Agent for Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory chronic disease characterized by inflammation, pain, swelling and disability, and radiosynovectomy is one of the disease treatment lines. In this study, the possibility of providing rhenium-186/rhenium-188 chitosan radiopharmaceuticals, optimization of conditions for their production and bio-distribution are reported. OBJECTIVE: In order to build perrhenic acid for labeling, natural rhenium was exposed to radiation. Radionuclidic and radiochemical purities of (186/188Re)-NaReO4 were examined by gamma spectroscopy and paper chromatography methods, respectively. METHODS: Labeling of chitosan with rhenium was done in different acidic situations. The radiochemical purity 186/188Re-chitosan was applied by radio thin layer chromatography (RTLC). Lastly, the bio-distribution of the radiolabeled chitosan was studied in various organs after intra articular injection of the complex to lab rats. Gamma spectrometry confirmed the high rhenium radionuclidic purity. Chromatography results showed that perrhenic acid was produced with purity greater than 97% and rhenium chitosan labeling was done over 98% in pH = 3. Dissection results showed a high bio-distribution of 186/188Re-chitosan after injection into the joint with no leakage to surrounding organs. CONCLUSION: According to the results, there is a possibility of labeling rhenium with chitosan in very high radiochemical purity. Regarding the high retention of these radiopharmaceuticals in joints with no leakage to surrounding organs, 186/188Re-chitosan can be applied as new radiosynovectomy drugs for rheumatoid arthritis treatment.

ESTIMATION OF HUMAN DOSE OF 188/186RE-HEDP COCKTAIL BASED ON OLINDA/EXM AND DISTRIBUTION DATA IN RATS.

188Re and 186Re are two applicable rhenium medical radioisotopes with complementary features that make them beneficial for different sizes of tumours. The aim of this study is to investigate 188/186Re-HEDP efficacy as a cocktail by calculating absorbed radiation dose in human organs based on biodistribution data obtained by injecting it to normal rats. Three rats were sacrificed at different time intervals and the percentage of injected dose per gram of each organ was measured by direct counting from rat data. By calculating accumulated activities in each organ and extrapolating rat data to human data by the radiation dose assessment resource method and by using OLINDA/EXM software, the injected dose in various human organs was obtained. The calculated absorbed dose showed that the 188/186Re-HEDP has noticeable properties that can be more helpful in comparison with using each of the rhenium radioisotopes separately.

177Lu/153Sm-Ethylenediamine Tetramethylene Phosphonic Acid Cocktail: A Novel Palliative Treatment for Patients with Bone Metastases.

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.

Highly Stable 177Lu-Organic Framework as a Potential Agent for Treatment of Metastatic Bone.

In this paper, the metal organic framework (MOF) concept is contributed to rearrange the bone-seeking agent composed of carrier-free lutetium-177 (Lu-177), 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraaminomethylenephosphonate (DOTMP) and cupper (II) (Cu (II)) for preparation of a potential agent for treatment of bone metastases. The product was characterized (infra-red spectroscopy, IR, and X-ray diffraction analysis) and quality-controlled (radio-thin layer chromatography, (RTLC)). The stability and in vitro hydroxyapatite binding was checked up to 1.5 month at 37 °C in human serum. Radio-MOF crystals and radio-MOF particles that were obtained by varying the synthesizing conditions (including pH and temperature) showed similar IR patterns and similar elemental analysis results. The final product was synthesized at pH = 8, stirring at room temperature (yield >99%, RTLC, particle size: 90 ± 20 nm). Biodistribution study experiments showed interesting bone-seeking (%ID/g: 8.5%) affinity of the prepared formula with no significant liver or lung uptake. Also high accumulation of radio-complex in bone tissue was estimated by the modeling of the radiation dose delivery using radiation dose assessment resource software. This novel radio-MOF with promising therapeutic results is the first study of the usage of the MOF concept to provide a high payload of Lu-177 for treatment of bone metastases. As it was expected, the most important outcome of the paper was higher bone-uptake rates rather than conventional 177Lu-DOTMP.

Feasibility study for production and quality control of Yb-175 as a byproduct of no carrier added Lu-177 preparation for radiolabeling of DOTMP.

Skeletal uptake of ß- emitters of DOTMP complexes is used for the bone pain palliation. In this study, two moderate energy ß- emitters, 177Lu (T1/2 = 6.7 days, Eßmax = 497 keV) and 175Yb (T1/2 = 4.2 days, Eßmax = 480 keV), are considered as potential agents for the development of the bone-seeking radiopharmaceuticals. Since the specific activity of the radiolabelled carrier molecules should be high, the non-carrier-added (NCA) radionuclides have an effective role in nuclear medicine. Many researchers have presented the synthesis of NCA 177Lu. Among these separation techniques, extraction chromatography has been considered more capable than other methods. In this study, a new approach, in addition to production of NCA 177Lu by EXC procedure is using pure 175Yb that was usually considered as a waste material in this method but because of high radionuclidic purity of 175Yb produced by this method we used it for radiolabeling as well as NCA 177Lu. To obtain optimum conditions, some effective factors on separation of Lu/Yb by EXC were investigated. The NCA 177Lu and pure 175Yb were produced with radionuclidic purity of 99.99 and 99.97% respectively by irradiation of enriched 176Yb target in thermal neutron flux of 5 × 1013 n/cm2 s for 14 days. 177Lu-DOTMP and 175Yb-DOTMP were obtained with high radiochemical purities (> 95%) under optimized reaction conditions. Two radiolabeled complexes exhibited excellent stability at room temperature. 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 for two radiolabelled complexes.

Absorbed doses in humans from 188Re-Rituximab in the free form and bound to superparamagnetic iron oxide nanoparticles: Biodistribution study in mice.

Absorbed doses to human organs from 188Re-Rituximab in the free form and bound to superparamagnetic iron oxide nanoparticles were predicted from results of the radiopharmaceutical biodistribution studies in mice by the RADAR method. Overall, equivalent and effective doses to human organs from the radiopharmaceutical on the nanoparticles were higher because of the enhanced permeability and retention effect. Liver, spleen and kidneys received higher equivalent doses than other organs (5.29, 3.70 and 3.06mSv/MBq, respectively, for the free radiopharmaceutical and 6.12, 3.96 and 3.93mSv/MBq for the drug on the nanoparticles).

Preparation and evaluation of APTES-PEG coated iron oxide nanoparticles conjugated to rhenium-188 labeled rituximab.

Radioimmuno-conjugated (Rhenium-188 labeled Rituximab), 3-aminopropyltriethoxysilane (APTES)-polyethylene glycol (PEG) coated iron oxide nanoparticles were synthesized and then characterized. Therapeutic effect and targeting efficacy of complex were evaluated in CD20 express B cell lines and tumor bearing Balb/c mice respectively. To reach these purposes, superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized using coprecipitation method and then their surface was treated with APTES for increasing retention time of SPIONs in blood circulation and amine group creation. In the next step, N-hydroxysuccinimide (NHS) ester of polyethylene glycol maleimide (NHS-PEG-Mal) was conjugated to the APTES-treated SPIONs. After radiolabeling of Rituximab antibody with Rhenium-188 (T1/2=16.9h) using synthesized N2S4 chelator, it was attached to the APTES-PEG-MAL-SPIONs surface through thiol-maleimide coupling reaction. In vitro evaluation of the 188ReN2S4-Rituximab-SPION-complex thus obtained revealed that at 24 and 48h post-treatment effective cancer cell killing had been achieved. Bio-distribution study in tumor bearing mice showed capability of this complex for targeted cancer therapy. Active and passive tumor targeting strategies were applied through incorporated anti-CD20 (Rituximab) antibody and also enhanced permeability and retention (EPR) effect of solid tumors for nanoparticles respectively.

Production, quality control, and determination of human absorbed dose of no carrier added 177 Lu-risedronate for bone pain palliation therapy.

In this study, the radiocomplexation of risedronic acid, a potent bisphosphonate with a no carrier added (NCA) 177 Lu, 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 ß- emitter, 177 Lu (T½  = 6.7 days, Eßmax  = 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 177 Lu production; among these separation techniques, extraction chromatography has been considered more capable than other methods. The NCA 177 Lu was produced with specific activity of 48 Ci/mg and radionuclidic purity of 99.99% by the irradiation of enriched 176 Yb target in thermal neutron flux of 4 × 1013  n·cm-2 ·s-1 for 14 days. The NCA 177 Lu 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 177 Lu-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.

Production and quality control 177Lu (NCA)-DOTMP as a potential agent for bone pain palliation.

Skeletal uptake of radiolabeled-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetramethylene phosphoric acid (e.g., 177Lu-DOTMP) complex, is used for bone pain palliation. The moderate energy of ß-emitting 177Lu (T½ = 6.7 d, Eßmax = 497keV) has been considered as a potential radionuclide for development of the bone-seeking radiopharmaceutical. Since the specific activity of the radiolabeled carrier molecules should be high, the "no-carrier-added radionuclides" have sig-nificant roles in nuclear medicine. Many researchers illustrated no-carrier-added 177Lu production; among these separation techniques such as ion exchange chromatography, reversed phase ion-pair, and electrochemical method, extraction chromatography has been considered more capable than other methods. In order to optimize the conditions, some effective factors on separation of Lu/Yb were investigated by EXC. The NCA 177Lu, produced by this method, was mixed with 300 µl of DOTMP solution (20 mg in 1 mL of 0.5 M NaHCO3, pH = 8) and incu-bated under stirring at room temperature for 45 min. Radiochemical purity of the 177Lu-DOTMP complex was determined using radio-thin-layer chromatography (RTLC) method. The complex was injected to wild-type rats and biodistribution was then studied for seven days. The NCA 177Lu was produced with specific activ-ity of 48 Ci/mg and with a radinuclidic purity of 99.99% through irradiation of enriched 176Yb target (1 mg) in a thermal neutron flux of 4 × 1013 n.cm-2.s-1 for 14 days. 177Lu-DOTMP was obtained with high radiochemical purities (> 98%) under optimized reaction conditions. The radiolabeled complex exhibited excellent stability at room temperature. Biodistribution of the radiolabeled complex studies in rats showed favorable selective skeletal uptake with rapid clearance from blood along with insignificant accumulation within the other nontargeted organs.

Development of an electrochemical 188W/188Re generator as a technique for separation and purification of 188Re in radiopharmaceutical applications.

In this study, a simple electrochemical procedure adaptable for using low specific activity 188W for separation and purification of 188Re from 188W to obtain no carrier added (NCA) 188Re is developed. The electrochemical parameters were optimized to maximize the 188Re electrodeposition yield with minimal 188W contamination. Two cycle electrolysis procedure was developed. The first electrochemical cell was used for separation of 188Re and in the second electrochemical cell, separation and purification of 188Re with >90% deposition yield of 188Re and minimal contamination of 188W (<10-4%) was achieved. The overall electrodeposition yield of 188Re was >90% with >99% radionuclidic purity and >99% radiochemical purity suitable for radiopharmaceutical applications. Furthermore, the performance of the generator remained consistent during a period of 69 days, one half-life of 188W, when the electrochemical separation procedure was performed frequently, at least once in 5 days.

Effect of low molecular weight organic acids on the uptake of 226Ra by corn (Zea mays L.) in a region of high natural radioactivity in Ramsar-Iran.

To study the benefit of including citric and oxalic acid treatments for phytoremediation of 226Ra contaminated soils a greenhouse experiment with corn was conducted. A soil was sampled from a region of high natural 226Ra radioactivity in Ramsar, Iran. After cultivation of corn seed and using organic acid treatments at 1, 10 and 100 mM concentrations, plants (shoots and roots) were harvested, digested and prepared to measure 226Ra activity. Simultaneously, sequential selective extraction were performed to estimate the partitioning of 226Ra among geochemical extraction. Results showed that the maximum uptake of 226Ra in plants was observed in citric acid (6.3%) and then oxalic acid (6%) at 100 mM concentration. These treatments increased radium uptake by a factor of 1.5 than the control. Enhancement of radium uptake by plants was related to soil pH reduction of organic acids in comparison to control. Also, the maximum uptake of this radionuclide in all treatments was obtained in roots compared to shoots. 226Ra fractionations results revealed that 91.8% of radium was in the residual phase of the soil and the available fractions were less than 2%. As the main percent of 226Ra was in the residual phase of the soil in this region, it seems that organic acids had not significant effect on the uptake of 226Ra for phytoremediation by corn in this condition.

Samarium-153-(4-[((bis (phosphonomethyl)) carbamoyl) methyl]-7,10-bis (carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl) acetic acid: A novel agent for bone pain palliation therapy.

AIM: Various phosphonate ligands labeled with ß--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.

Preparation, quality control and biodistribution assessment of ¹5³Sm-BPAMD as a novel agent for bone pain palliation therapy.

OBJECTIVE: Various phosphonate ligands labeled with ß(-)-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.

Metastatic Bone Pain Palliation using (177)Lu-Ethylenediaminetetramethylene Phosphonic Acid.

(177)Lu-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 (177)Lu-EDTMP for MBP palliation. (177)Lu-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. (177)Lu-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. (177)Lu-EDTMP has shown suitable physical and biological properties with good results in long term bone pain relief for patients with bone metastasis.

Development of (166)Holmium-1,2 Propylene Di-amino Tetra (Methy1enephosphonicacid) as a Possible Bone Palliation Agent.

(166)Holmium-1,2-propylene di-amino tetra (methy1enephosphonicacid) ((166) Ho-PDTMP) complex was prepared successfully using an in-house synthesized PDTMP ligand and (166) HoCl 3 . Ho-166 chloride was obtained by thermal neutron irradiation (1 × 10 (13) n/cm (2) /s) of natural Ho (NO 3 ) 3 samples (specific activity = 3-5 GBq/mg), dissolved in acidic media. Radiochemical purity of (166) Ho-PDTMP was checked by instant thin layer chromatography (>99%). Stability studies of the complex in the final preparation and in the presence of human serum were performed up to 72 h. The biodistribution of (166) Ho-PDTMP and (166) HoCl 3 in wild-type rats was checked in animal tissues up to 48 h. The produced (166) Ho-PDTMP properties suggest a possible new bone palliative therapeutic to overcome the metastatic bone pains.

Thermoluminescent and Monte Carlo dosimetry of a new 170Tm brachytherapy source.

In this Study characteristics of a new 170Tm brachytherapy seed using thermoluminescent dosimeter and also the Monte Carlo simulations to evaluate between calculated and measured values was determined. Titanium tube contained Tm(NO3)3 powders bombardment at the Tehran Research Reactor (TRR) for a period of 7 days at a flux of 2-3 × 10(13) neutrons/cm2 s. To obtain the radial dose function, g(r), and the anisotropy function, F(r, θ), according to the AAPM TG-43U1 recommendations, 30 cm × 30 cm × 15 cm phantoms of Perspex slabs were used. Brachytherapy dose distributions were simulated with the MCNP5 Monte Carlo (MC) radiation transport code. The MCPLIB04 photon cross-section library was applied using data from ENDF/B-VI. Cell-heating tally, F6 was employed to calculate absorbed dose in two separate runs for both beta and gamma particles. The calculated dose rate constant for the HDR source was found to be 1.113 ± 0.021 cGyU(-1) h(-1). Nominal uncertainty in the measured and calculated radial dose functions, g(r), for the IR-(170)Tm source in Perspex is tabulated is approximately 6% (ranging from 2% to 9%). The anisotropy function, F(r, θ), of the IR-(170)Tm source was measured at radial distances of r = 1.5, 2, 3, 5 cm relative to the seed center, and polar angles θ ranging from 0° to 330° in 30° increments.

Development of (177)Lu-phytate Complex for Radiosynovectomy.

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 × 10(13) n.cm(-2).s(-1). The product was converted into chloride form which was further used for labeling of (177)Lu-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.

Production, Quality Control and Biological Evaluation of (166)Ho-PDTMP as a Possible Bone Palliation Agent.

OBJECTIVE(S): In this study, (166)Ho-1,2-propylene di-amino tetra(methy1enephosphonicAcid) ((166)Ho-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 (166)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 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). (166)Ho-PDTMP complex was stabilized in the final preparation and in the presence of human serum (>90%) up to 72 hr. The biodistribution of (166)Ho-PDTMP in wild-type rats demonstrated significant bone uptake was up to 48 hr compared to (166)HoCl3. CONCLUSION: The produced (166)Ho-PDTMP properties suggest a possible new bone palliative therapeutic to overcome the metastatic bone pains.

Optimization of 90 Y-antiCD20 preparation for radioimmunotherapy.

CONTEXT: The advent of monoclonal antibodies such as Rituximab, in recent years, has brought about decisive progress in the treatment of aggressive and indolent non-Hodgkin's lymphoma. AIMS: A further tried and tested improvement to the unmodified antibody has been its coupling to the beta-emitters Y-90. The optimization of 90 Y-antiCD20 radioimmunoconjugate production and quality control methods for future clinical studies in the country was targeted in this work. MATERIALS AND METHODS: The antibody was labeled with 90 Y-yttrium chloride (185 MBq) after conjugation with freshly prepared ccDTPA. Y-90 chloride was obtained by thermal neutron flux (4 × 10 13 n/cm 2 /s) of a natural Y 2 O 3 sample, dissolved in acidic media. Radiolabeling was completed in 24 h by the addition of DTPA-Rituximab conjugate at room temperature. STATISTICAL ANALYSIS USED: All values were expressed as mean ± standard deviation (mean ± SD), and the data were compared using Student's t-test. Statistical significance was defined as P < 0.05. RESULTS: Radiochemical purity of 96% was obtained by using ITLC method for the final radioimmunoconjugate (specific activity = 440-480 MBq/mg). The final isotonic 90 Y-Rituximab complex was checked by gel electrophoresis for protein integrity retention. Biodistribution studies in normal rats were carried out to determine the radioimmunoconjugate distribution up to 72 h. CONCLUSION: The results showed that 90 Y-DTPA-Rituximab could be considered for further evaluation in animals and possibly in humans as a radiopharmaceutical for use in radioimmunotherapy against non-Hodgkin's lymphomas. Because of the importance of developing anti-lymphoma B agents in nuclear medicine for country use, an optimized radiolabeling method has been introduced.

Production, Quality Control and Pharmacokinetic Studies of (177)Lu-EDTMP for Human Bone Pain Palliation Therapy Trials.

Developing new bone pain palliation agents is a mandate in handling end-stage cancer patients around the world. Possibly, Lu-177 ethylenediaminetetramethylene phosphonic acid ((177)Lu-EDTMP) is a therapeutic agent which can be widely used in bone palliation therapy. In this study, (177)Lu-EDTMP complex was prepared successfully using synthesized EDTMP ligand and (177)LuCl3. Lu-177 chloride was obtained by thermal neutron irradiation (4 × 10(13) n.cm(-2)s(-1)) of natural Lu2O3 samples. Radiochemical purity of (177)Lu-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 (177)Lu-EDTMP and (177)LuCl3 in wild-type rats was studied by SPECT imaging. A comparative accumulation study for (177)Lu-EDTMP and (177)LuCl3 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, (177)Lu-EDTMP seemed to be an interesting new candidate for clinical trials for bone pain palliation therapy.