Introduction: Bone metastases are a frequent complication of cancer that frequently causes intense pain. Pain palliation of these cancers is one of important goals in nuclear medicine. Therapeutic radiopharmaceuticals are widely used to palliate pain of bone metastases. Among some radiopharmaceuticals which are useful for radiotherapy, holmium-166 ethylenediamine-tetramethylenephosphonicacid (166Ho-EDTMP) is of particular interest for larger tumors.166Ho is a beta and gamma emitter with a high beta energy and appropriate halflife and gamma ray (81 keV) for imaging studies.Methods: 166Ho was prepared by neutron activation of natural 165Ho sample (purity >99/8%) and complex was obtained in room temperature by adding EDTMP ligand. In this research radiochemical purity was checked by paper chromatography and radionuclidic purity by recording the gamma ray spectra using a gamma spectrometer with an HPGe detector. The biodistribution studies of radiopharmaceutical, then was performed using wild type rats. In addition, the image was taken at 4 hours after administration of the radiopharmaceutical by a dual-head SPECT system.Results: 166Ho-EDTMP was prepared in excellent purity (above 99% in 30 minutes) and with high in-vitro stability. The major deposition of radiopharmaceutical (>70%) was found in bone, while radiopharmaceutical did not practically accumulate in other organs.Conclusion: 166Ho-EDTMP is a promising agent for bone pain palliation therapy in skeletal metastases in human with low undesired dose to other organs in rodents.

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.

Introduction: In this research, [166Ho] Holmium chitosan complex production is described in details, followed by determination of complex radiochemical purity, stability and biodistribution (after intra-articular injection) in wild-type male rats. Finally a Ho-166 based chitosan kit for ultimate radiosynovectomy as well as radiotherapy applications was developed.Methods: 166Ho-chitosan complex was prepared using chitosan concentrations and 166HoCl3 followed by intra-articular injection and biodistribution studies in wild-type rats including and excluding injected knee.Results: The [166Ho] Holmium chitosan complex was prepared with high radiochemical yield (>95 %) in the optimized condition (35mg/3ml of chitosan  in %1 AcOH, pH. 3, >98%, ITLC) was injected to wild-type rats followed by the biodistribution studies of the compound among the tissues excluding the injected knee data. Intra-articular injection of [166Ho] holmium chitosan complex to male wild-type rats and investigation of leakage of activity in the body showed that most of injected dose has remained in injection site 144 h after injection. Conclusion: Successful development and formulation of 166Ho-chitosan kit is described. This kit has the potential for use in clinical setting namely for radiosynovectomy and cancer radiochemotherapy.

Introduction: Recently, due to the special characteristics of 166Ho and chitosan, 166Ho-chitosan complex was developed for treatment of tumors such as hepatocellular carcinoma. This complex has been lately prepared with high radiochemical purity in our lab. The preclinical studies of the complex however should be performed to evaluate the tracer concentration in target and normal tissues before human use.Methods: In this study, 166Ho-chitosan was prepared and its preclinical studies for treatment of hepatocellular carcinoma was carried out by injection of the radiopharmaceutical into the rabbit`s liver via two different methods, surgery and venography. Leakage of the injected activity from the injection site in the rabbit organs was investigated using SPECT and SPECT-CT imaging up to 24 hours.Results: Both SPECT and SPECT-CT imaging of the rabbits showed that there was no significant leakage of the injected activity. Almost all the activity would remain in the injection site at least 24 h post injection.Conclusion: Considering all of the excellent features of the complex, this radiopharmaceutical is suggestive for treatment of hepatocellular carcinoma by radioembolization method.

177Lu-EDTMP complex is proposed as a proper alternatives to other radiopharmaceuticals as the relatively long half-life (T1/2=6.71 days), maximum energyb- particle Eb-=498keV (78.6%), low abundance gamma emission 208keV (11%), 111keV (6.4%) and easy production are considered advantageous in the wider use of this product. In this study, 177Lu was produced by thermal neutron bombardment on 176Lu2O3 target in the 5MW Tehran Research Reactor. Radionuclide purity of the 177Lu was ascertained by recording the gamma ray spectra using a gamma spectrometer with an HPGe detector. 177Lu-EDTMP complex was prepared at room temperature. The radiochemical purity of the preparation was determined by thin layer chromatography which showed high purity of more than 98% for the resulted complex. The quality control and biodistribution studies of 177Lu-EDTMP were performed in wild-type rats. The result showed favorable biodistribution features of 177Lu-EDTMP, indicating significant accumulation in bone. Also, it was observe that clearance of the activity from other organs happens after 7 days. This research presents 177Lu-EDTMP as a suitable therapeutic radiopharmaceutical with proper half-life and low dose for bone palliation of skeletal metastases.

Introduction: Involvement of the skeleton can cause an excruciating pain in two-thirds of terminal patients with a history of malignancy. Due to several limitations of other therapies, such as analgesics, bisphosphonates, chemotherapy, hormonal therapy and external beam radiotherapy; bone-seeking radiopharmaceuticals have an important role in palliation of pain from bone metastases. Although these kinds of therapies have many advantages including the ability to treat multiple sites of tumoral involvement simultaneously, no significant confliction with other treatments, ease of administration and the potential to be used repetitively; in Iran using of this modality is not widely practiced. In this study we evaluated the clinical usefulness of Sm-153 lexidronamfor pain management of bone metastases.Methods: 28 patients (14 males and 14 females) aged 38-77 years with a history of painful bone metastases caused by different cancers, not responding to conventional treatments were included in the study. All patients had a recent whole body bone scan indicating multiple bone metastases.1 mCi/Kg Sm-153 lexidronam was injected intravenously to the patients. Whole body scintigraphy was done 3 or 18 hours post injection. Pain relief and quality of life have been evaluated by analog pain scale and Karnofsky index every week, respectively. Also, all patients were evaluated for hematological toxicity every two weeks. Active follow ups were performed.Results: 43% of patients showed the presence of the flare phenomenon during the first three days after Sm injection with a mean duration of 2.2 days. The pain relief began between 2 and 16 days post injection and the duration of pain palliation was in the range of 4 to 32 weeks (mean±SD=15.22±7.8).64.3% of patients showed complete relief of pain and 21.4% achieved partial response to therapy. (Over all response to therapy was 85.7%). The lowest amount of peripheral blood cells was detected in the fourth week for RBCs and in the 6th week for WBCs and PLTs. No one experienced hematological toxicity induced problems.Conclusion: Sm-153 lexidronam is an effective treatment for painful bone metastases. The complication rate is low and the quality of life of the patients after treatment would be significantly improved.

Introduction: The importance of existence and application of radiolabeled anti-CD20 monoclonal antibodies at nonmyeloablative doses in treating B-cell NHL is well recognized throughout the world. In this work, anti-CD20 was successively labeled with beta-particle emitting radionuclide, Ho-166, for ultimate radioimmunotherapy applications.Methods: Ho-166 chloride was obtained by thermal neutron flux (1 × 1013 n.cm-2.s-1) of natural Ho2 (NO3) 3 sample, dissolved in acidic media.166Ho-holmium chloride (185 MBq) was added to the conjugated antibody after ccDTPA residulation at room temperature. Radiochemical purity was determined using HPLC and ITLC. The final isotonic 166Ho-rituximab complex was checked by gel electrophoresis for protein integrity retention. Biodistribution studies of Ho-166 chloride and radioimmunoconjugate were performed in wild-type rats to determine the biodistribution.Results: The radioimmunoconjugate was prepared with a radiochemical purityof 95% (ITLC) and 98% (HPLC) (Specific activity=3-3.5 GBq/mg). The final compound was stable in presence of human serum at 37°C and at room temperature. The samples were showed to have similar pattern of migration in the gel electrophoresis. The accumulation of the radiolabeled antibody in lungs, liver and spleen demonstrates a similar pattern to the other radiolabeled anti-CD20 immunoconjugates.Conclusion: 166Ho-rituximab is a potential compound for therapy of lymphoma B patients. The experiments on lymphoma animal models should be performed for this radioimmunoconjugate before human use.

Introduction: Targeted radionuclide therapy (TRT) has been demonstrated to be an effective therapeutic tool in patients with disseminated bone metastasis. TRT is generally performed with a single radionuclide. In this study we investigated the feasibility of combined TRT with a high-energy beta emitter (153Sm) and a low energy beta emitter (177Lu) in wistar rats.Methods: The cocktail complex of 153Sm/177Lu-EDTMP was prepared. To determine the effect of metal-to-ligand (Me: EDTMP) molar ratio on labeling yield, several complex were analyzed after changing Me: EDTMP molar ratio from 1: 1 to 1: 50.153Sm/177Lu-EDTMP was administered intravenously through the tail vein of wistar rats. Biodistribution data were collected at 2 hours to 7 day post injection and scintigraphic images were taken at 24 hours and 1, 2 week after administration of radiopharmaceutical.Results: The results revealed high skeletal uptake (3.5% and 3.4% ID/g at 24 hours post injection for 153Sm and 177Lu, respectively) with rapid blood clearance and minimal uptake in any of the major organs. Scintigraphic images verified high skeletal uptake.Conclusion: Our results indicate that the combination of 153Sm and 177Lu is feasible and safe. This study suggests that the combination of different radionuclides with different radiation energies and half-life, such as 153Sm and 177Lu, could be advantageous in patients with tumoral lesions of different sizes.