ABSTRACT
Objective[s]: recently, bone-avid radiopharmaceuticals have been shown to have potential benefits for the treatment of widespread bone metastases. Although 177Lutriethylene tetramine hexa methylene phosphonic acid [abbreviated as 177Lu- TTHMP], as an agent for bone pain palliation, has been evaluated in previous studies, there are large discrepancies between the obtained results. In this study, production, quality control, biodistribution, and dose evaluation of 177Lu-TTHMP have been investigated and compared with the previously reported data
Methods: TTHMP was synthesized and characterized, using spectroscopic methods. Radiochemical purity of the 177Lu-TTHMP complex was determined using instant thin-layer chromatography [ITLC] and high performance liquid chromatography [HPLC] methods. The complex was injected to wild-type rats and biodistribution was studied for 7 days. Preliminary dose evaluation was investigated based on biodistribution data in rats
Results: 177Lu was prepared with 2.6-3 GBq/mg specific activity and radionuclide purity of 99.98%. 177Lu-TTHMP was successfully prepared with high radiochemical purity [>99%]. The complex showed rapid bone uptake, while accumulation in other organs was insignificant. Dosimetric results showed that all tissues received almost insignificant absorbed doses in comparison with bone tissues
Conclusion: based on the obtained results, this radiopharmaceutical can be a good candidate for bone pain palliation therapy in skeletal metastases
ABSTRACT
Rheumatoid arthritis [RA] is the most common autoimmune disease, leading to the destruction of the joints and causing pain, disability, and immobility in the patients. Radiosynovectomy [RSV] has been applied as an effective treatment for the patients with resistant synovitis after failure of long-term pharmacotherapy and intra-articular steroid injection for more than 50 years. Several radiopharmaceuticals have been developed for RSV so far, but still development of new radiophamaceuticals is of crucial interest. In this research, the [177]Lu-chitosan complex [[177]Lu-CHITO] was introduced as a new agent for RSV. [177]Lu was produced by irradiation of a natural Lu2O3 target at a thermal neutron flux of approximately 4 x 10[13] n/cm[2]s. [177]Lu-CHITO was prepared in the diluted acetic acid solution. The radiochemical yield was checked by ITLC method. The biodistribution of the complex was investigated by intra-articular injection to rabbits' and rats' knee joints. The leakage of injected dose from the injection site in the rabbit organs was investigated using SPECT imaging up to 48 hours. [177]Lu was prepared with a specific activity of 2.6-3 GBq.mg[-1] and radionuclide purity of 99.98%. [177]Lu-CHITO was prepared successfully with high radiochemical purity [95%] and specific activity of 888 TBq/mmol. Both the biodistribution data in rats and SPECT imaging of the rabbit showed that there was no significant leakage of the injected activity even after 192 h. Considering all of the excellent features of the complex, this radiopharmaceutical can be used for effective management of synovial inflammation
ABSTRACT
Due to the anti-proliferative properties of platinum group-thiosemicarbazone complexes, the production of [191]Os-labeled 2-acetyl pyridine 4-N-methylthiosemicarbazone [[191]Os-APMTS] was investigated. [[191]Osmium [T[1/2]= 15.4d] was produced via the [190]Os[n,gamma][191]Os nuclear reaction using enriched target irradiated with thermal neutrons. Reaction of in-house synthesized 2-acetylpyridine thiosemicarbazone [APMTS] with [191]Os yielded [[191]Os]APMTS checked by ITLC followed by stability, partition co-efficient and biodistribution determination. Following synthesis and spectroscopic determination of the ligand [>99% chemical purity], the complex was prepared with a radiochemical purity of more than 95% [RTLC] and specific activity of 21.5 GB/mM and was stable in the formulation and presence of human serum at 37[degree sign]C for up to 48h. The partition coefficient was determined [log P. 1.23]. The biodistribution study up to 4 days demonstrated significant tissue uptake differences in the bone, blood, heart and thyroid. This is the first Os-191 labeled thiosemicarbazone designed as an in-vivo therapeutic radionuclide generator. Further investigation is ongoing on the evaluation of the complex in tumor bearing animals
Subject(s)
Animals, Laboratory , Osmium , Radioisotopes , Radionuclide GeneratorsABSTRACT
Due to interesting therapeutic properties of [46]Sc and antineoblastic antibiotic, bleomycin [BLM], 46Scbleomycin [[46]Sc-BLM] was developed as a possible therapeutic compound. In this work, Sc-46 chloride was obtained by thermal neutron flux [4 × 10[13] n.cm[-2].s[-1]] of natural metallic scandium sample followed by dissolution in acidic media as a substitute for [47]Sc in radiolabeling studies which was further used for labeling of bleomycin [BLM] followed by stability studies as well as biodistribution in wild-type rats. Sc-46 was obtained in high radiochemical purity [ITLC, >99%, two systems] as well as acceptable specific activity. At optimized conditions a radiochemical purity of 98% was obtained for [46]Sc-BLM shown by ITLC [Specific activity, 740 GBq/mmole]. The accumulation of the radiolabeled compound in lungs, liver and spleen demonstrates a similar pattern to the other radiolabeled bleomycins. Sc-BLM is a possible therapeutic agent in human malignancies and the efficacy of the compound should be tested in various tumor-bearing models
Subject(s)
Animals, Laboratory , Radioisotopes , Scandium , Drug Compounding , Quality Control , RatsABSTRACT
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]LuCl[3]. Lu-177 chloride was obtained by thermal neutron irradiation [4 _ 10[13] n.cm[-2]s[-1]] of natural Lu[2]O[3] 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]LuCl[3] in wild-type rats was studied by SPECT imaging. A comparative accumulation study for [177]Lu-EDTMP and [177]LuCl[3] 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
ABSTRACT
Therapeutic radiopharmaceuticals are radiolabeled molecules to deliver sufficient doses of ionizing radiation to specific disease sites such as bone metastases, brain and liver tumors and bone marrows malignancies including multiple myeloma. Among some therapeutic radiopharmaceuticals, 166Ho-1, 4, 7, 10-tetraazacyclo dodecane-1,4,7,10 tetraethylene phosphonic acid [166Ho-DOTMP] is used for delivering high doses to bone marrow. In this research production, quality control, pharmacokinetics and biodistribution studies of 166Ho-DOTMP with respect to its radiochemical and in vivo biological characteristics have been presented. Holmium-166 was produced by irradiation of holmium oxide [Ho2O3, purity>99.8%] at a thermal neutron flux. 166Ho-DOTMP complex was obtained in very high yields [radiochemical purity>99%] under the reaction conditions employed. Radiochemical purity and the stability of the 166Ho-DOTMP complex in human serum were assayed. Wild type rats were used for biodistribution and imaging studies of this agent. 166Ho produced by irradiation of holmium-165 oxide demonstrated high radionuclide purity. 166Ho-DOTMP was obtained in very high yield [radiochemical purity>99%] and the complex exhibited excellent in vitro stability at pH-7 when stored 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. The scintigraphic image recorded in rat at 3 h after the injection of the 166Ho-DOTMP radiopharmaceutical revealed that 166Ho-DOTMP rapidly accumulated in skeleton especially in the thigh bones. Biodistribution, stability, imaging and pharmacokinetics studies of 166Ho-DOTMP radiopharmaceutical in this research showed favorable features such as; rapid and selective skeletal uptake, fast clearance from blood and almost no uptake in any other major organs. Our research demonstrated that 166Ho-DOTMP has promising features suggesting good potential for efficient use of this radiopharmaceutical for bone marrow ablation in different hematologic malignancies including multiple myeloma
ABSTRACT
Various bone palliative therapeutic agents have been developed and widely used for bone metastasis such as [153]Sm-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. [153]Sm-TTHMP was prepared starting from [153]Sm-SmCl[3], prepared by neutron activation of an enriched [152]Sm sample [purity >98%], and in-house synthesized TTHMP in 1h at 25[degree sign] C followed by stability tests, partition coefficient determination and biodistribution studies of in wild-type rodents using scarification and SPECT imaging. The radiolabled Sm complex was prepared in high radiochemical purity [>99%, ITLC] and specific activity of 278 GBq/mmol and demonstrated significant ability at 4, 25 and 37 [degree sign] C [in presence of human serum]. Initial biodistribution data showed significant bone accumulation of the tracer in 48h. [153]Sm-TTHMP can be a potential candidate for bone pain palliation therapy in skeletal metastases, although further biological studies in other mammals is still needed
Subject(s)
Animals, Laboratory , Rats , Bone Neoplasms/secondary , Quality Control , Neoplasm Metastasis , Palliative Care , Radioisotopes , Organometallic Compounds/chemical synthesisABSTRACT
Developing new radiosynovectomy agents is of great importance due to the aging of human populations around the world and increasing the incidence of inflammatory diseases. In this work, Sm-153 chitosan agent was developed for the first time in our country and preparation and quality control of the compound is described. Sm-153 chloride was obtained by thermal neutron flux [4-5 x 10[13] n.cm [-2]. S[-1] of natural Sm[2]O[3] sample, dissolved in acidic media. [153] Sm-samarium chloride [370 MBq] was used in preparation of [153] Sm-chitosan complex followed by quality control using MeOH: H[2]O: acetic acid [4: 4: 2] as mobile phase. The complex stability and viscosity were checked in the final solution up to 2 days. The complex solution and [153]Sm[3+] [80 micro Ci/100 micro l] were injected intra-articularly into male rat knee joint followed by scarification studies 6d post injection. Sm-153 chitosan was prepared successfully with high radiochemical purity [>99%, ITLC] at room temperature after 10-30 min followed by autoclave sterilization. The complex was stable at room temperature and 37 [degree sign] C up to 2 days. No significant leackage of dose from injection site and its distribution in organs were observed up to 6 days for [153] Sm-chitosan. Approximately, more than 90% of injected dose remained in injection site after 6d. The complex is a dedicated agent for radiosynovectomy. The experience from this study would lead to the development of more sophisticated radiosynovectomy radiopharmaceuticals for human use in the country
ABSTRACT
Iranian scorpion species are classified in Buthidae and Scorpionidae with 16 genera and 25 species. In Iran, similar to other parts of the world, there are a few known species of scorpions responsible for severe envenoming. Mesobuthus eupeus is the most common species in Iran. Its venom contains several toxin fractions which can affect the ion channel. In this study purification, labeling and biological evaluation of Mesobuthus eupeus scorpion venom are described. To separate different venom fractions, soluble venom was loaded on a chromatography column packed with sephadex G50 gel then the fractions were collected according to UV absorption at 280 nm wavelength. Toxic fraction [F3] was loaded on anionic ion exchanger resin [DEAE] and then on a cationic resins [CM]. Finally toxic fraction F319 was labeled with [99m]Tc and radiochemical analysis was determined by paper chromatography. The biodistribution was studied after injection into normal mice. Toxic fraction of venom was successfully obtained in purified form. Radiolabeling of venom was performed at high specific activity with radiochemical purity more than 95% which was stable for more than 4 h. Biodistribution studies in normal mice showed rapid clearance of compound from blood [2.64% ID at 4 h] and tissues except the kidneys [27% ID at 4 h]. As tissue distribution studies are very important for clinical use, results of this study suggest that [99m]Tc labeling of venom can be a useful tool for in vivo studies and is an excellent approach to follow the process of biodistribution and kinetics of toxins
ABSTRACT
In this research, [[166]Ho]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. [166]Ho-chitosan complex was prepared using chitosan concentrations and [166]HoCl[3] followed by intra-articular injection and biodistribution studies in wild-type rats including and excluding injected knee. The [[166]Ho]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 [[166]Ho]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. Successful development and formulation of [166]Ho-chitosan kit is described. This kit has the potential for use in clinical setting namely for radiosynovectomy and cancer radiochemotherapy
ABSTRACT
It has been shown that some primary human tumors and their metastases, including prostate and breast tumors, over-express gastrin-releasing peptide [GRP] receptors. Bombesin is a neuropeptide with a high affinity for these GRP receptors. The purpose of this study was to prepare and evaluate the characteristics of a new Freeze-dried kit, [6-hydrazinopyridine-3-carboxylic acid [HYNIC]]-GABA-Bombesin [7-14] NH[2] designed for the labeling with 99mTc using tricine and EDDA as coligand. Synthesis was performed on a solid phase using a standard Fmoc strategy and HYNIC precursor coupled at the N-terminus. Purified peptide conjugate was labeled with [99m]Tc at 100°C for 10 min. Radiochemical analysis involved ITLC and high-performance liquid chromatography methods. Peptide conjugate stability and affinity to human serum was challenged for 24 hours. The internalization rate was studied in GRP receptor expressing PC-3 cells. Biodistribution of radiopeptide was studied in rats. Radiolabeling was performed at high specific activities, and radiochemical purity was >98%. The stability of radiolabeled peptide in human serum was excellent. In vitro studies showed >14% of activity was specific internalized into PC-3 cells up to 4 h. After injection into rat biodistribution data showed a rapid blood clearance, with renal excretion and specific binding towards GRP receptor-positive tissues such as pancreas [1.15 +/- 0.19% ID/g after 4 h]. [[99m]Tc-HYNIC]-GABA-Bombesin [7-14] NH[2] showed favorable radiochemical and biological characteristics which make our new designed labeled peptide conjugate as a very suitable agent for diagnostic purposes in malignant tumors
ABSTRACT
[[64]Cu]diacetyl-bis[N[4]-methylthiosemicarbazone] [[[64]Cu]ATSM] is a well-established hypoxia imaging tracer with reproducible production and significant specifity. In this work the high yield production and quality control as well as imaging studies in healthy rabbits is reported. Copper-64 produced via the [68]Zn[p, alpha n] [64]Cu nuclear reaction [30 MeV protons at 180 micro A] was used for the preparation of [[64]Cu]diacetyl-bis[N4-methylthiosemicarbazone][[ [64]Cu]ATSM]. Followed by quality control and administration to healthy rats as well as healthy rabbits for biodistribution and imaging studies respectively. [64]Cu[2+] [500 mCi, separation yield> 95%, radionuclide purity>96%] was used for [[64]Cu]ATSM production [radiochemical purity>99%, specific activity of 300 Ci/mmol] followed by administration to healthy rabbits and coincidence imaging demonstrating uptake in liver, kidney and bowel as shown by other reports in various rodents and human. [[64]Cu]ATSM radiopharmaceutical is produced and now available in large quantities for research and/or clinical trials in the country
ABSTRACT
Nowadays various bone pain palliative therapeutic agents have been developed for bone metastases. Among those, [153]Sm-ethylenediamine tetramethylene phosphonic acid [[153]Sm-EDTMP] is the major therapeutic agent which is widely used in the world. In this study, production, quality control and biodistribution studies of this therapeutic radiopharmaceutical have been presented and followed by imaging studies in a wild-type rabbit for the first time in order to make preparations for this agent to be officially approved in the country. [153]Sm-EDTMP was produced using [153]Sm-SmCl[3], prepared by neutron activation of an enriched [152]Sm sample [purity >98%], and in-house synthesized EDTMP in 4h at 100°C. The analytical data for the structure determination and purity of the ligand was obtained and shown to be identical to an authentic sample from a European vendor. The Radiochemical purity of [153]Sm-EDTMP was checked by RTLC and ITLC. The biodistribution of [153]Sm-EDTMP in wild-type rodents was checked and SPECT imaging as well as following sacrificing the animal. The radiolabeled Sm complex was prepared in high radiochemical purity [>99%, RTLC] followed by initial biodistribution data with the significant bone accumulation [>70%] of the tracer in 48h which is comparable with the reported methods. The produced [153]Sm-EDTMP properties suggest good potential for efficient use of this radiopharmaceutical for bone pain palliation and as substitute for other agents, such as [89]SrCl[2] and [32]P, currently used in the country