Preclinical studies of [68]Ga-DOTATOC: biodistribution assessment in Syrian rats and evaluation of absorbed dose in human organs

Objective[s]: Gallium-68 DOTA-DPhe[1]-Tyr[3]-Octreotide [[68]Ga-DOTATOC] has been applied by several European centers for the treatment of a variety of human malignancies. Nevertheless, definitive dosimetric data are yet unavailable. According to the Society of Nuclear Medicine and Molecular Imaging, researchers are investigating the safety and efficacy of this radiotracer to meet Food and Drug Administration requirements. The aim of this study was to introduce the optimized procedure for [68]Ga-DOTATOC preparation, using a novel germanium-68 [[68]Ge]/[68]Ga generator in Iran and evaluate the absorbed doses in numerous organs with high accuracy

Methods: The optimized conditions for preparing the radiolabeled complex were determined via several experiments by changing the ligand concentration, pH, temperature and incubation time. Radiochemical purity of the complex was assessed, using high-performance liquid chromatography and instant thin-layer chromatography. The absorbed dose of human organs was evaluated, based on biodistribution studies on Syrian rats via Radiation Absorbed Dose Assessment Resource Method

Results: [68]Ga-DOTATOC was prepared with radiochemical purity of >98% and specific activity of 39.6 MBq/nmol. The complex demonstrated great stability at room temperature and in human serum at 37[degree]C at least two hours after preparation. Significant uptake was observed in somatostatin receptor-positive tissues such as pancreatic and adrenal tissues [12.83%ID/g and 0.91%ID/g, respectively]. Dose estimations in human organs showed that the pancreas, kidneys and adrenal glands received the maximum absorbed doses [0.105, 0.074 and 0.010 mGy/MBq, respectively]. Also, the effective absorbed dose was estimated at 0.026 mSv/MBq for [68]Ga-DOTATOC

Conclusion: The obtained results showed that [68]Ga-DOTATOC can be considered as an effective agent for clinical PET imaging in Iran

Production, biodistribution assessment and dosimetric evaluation of [177]Lu-TTHMP as a bone pain palliation agent

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

Mismanagement of a huge ovarian serous cystadenoma in a young girl; a case report

While ovarian masses are common findings in gynecology, unusually huge masses are quite rare. However, such cases can still be found today. Mismanagement of common complaints in patients can be a leading cause of facing such findings. Herein, we introduce a case of a giant ovarian cyst, which was mismanaged in a young virgin female patient. The patient had received gastrointestinal medications for months before being admitted to our clinic, given the bloating sensation and lack of any gynecologic problems. Ultrasonography disclosed a giant cyst, probably related to the ovary, originating from the pelvis and extending toward the diaphragm. After a successful surgery, the ovarian cyst, measuring 40 centimeters and weighing 8 kilograms, was removed. Pathology report revealed serous cystadenoma. Existence of such cases can be an alarming sign for physicians to manage prevalent complaints more seriously, particularly those non-responsive to treatment

Preparation and quality control of [177]Lu-chitosan for radiosynovectomy

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

Radiosynthesis and evaluation of ytterbium-175 labeled bleomycin as therepeutic agent

Bleomycins are DNA-binding biomolecules, which can be used as targeted therapy carriers when labeled with particle-emitters such as Yb-175. In this work the development of Yb-175 bleomycin [[175]Yb-BLM] has been reported. Yb-175 chloride was obtained by thermal neutron irradiation [3 × 10[13] n.cm[-2].s[-1]] of natural Yb2O3 samples at various neutron fluxes and irradiation times. The radionuclide dissolved in acidic media [120mCi/mg] was used in the bleomycin [5 mg] labeling in buffer solution and warming at 60[degree sign]C for 48 h. Radiochemical purity was determined by ITLC as well as specific activity calculation followed by stability studies. Biodistribution studies of free Yb-175 and [175]Yb-BLM were performed in wild-type mice up to 8 days. At optimized conditions radiochemical purity of 97 +/- 0.88% and specific activity of 1360 MBq/mM was obtained. Biodistribution studies of free Yb-175 demonstrated liver and bone uptake while in case of [175]Yb-BLM the target tissues were lung, liver and spleen.[175]Yb-BLM complex was prepared at the optimized conditions and suitable characteristics. The accumulation of the radiolabeled compound in lungs, liver and spleen demonstrates a similar pattern to the other radiolabeled bleomycins. Further studies are to be performed for application of this labeled compound in tumor-bearing models

Radiosynthesis of [191]Os-2-acetylpyridine thiosemicarbazone complex, as an in vivo therapeutic radionuclide generator

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

Radiosynthesis and quality control of [[67]GA]-3,4-dimethoxylated porphyrin complex as a possible imaging agent

Radiolabeled porphyrins are potential tumor avid radiopharmaceuticals because of their impersonation in the human body, ability to complex various radionuclides, water solubility, low toxicity etc. In this work a radiogallium porphyrin complex has been developed. [67Ga] labeled 5,10,15,20-tetrakis [3,4-dimethoxyphenyl] porphyrin [[67Ga]-TDMPP] was prepared using freshly prepared [67Ga]GaCl[3] and 5,10,15,20-tetrakis [3,4-dimethoxyphenyl] porphyrin [H[2]TDMPP] for 60 min at 100°C. Stability of the complex was checked in final formulation and human serum for 24 h, followed by biodistribution and imaging studies in wild type rats up to 24 h. The radiocomplex was obtained with radiochemical purity >99% [ITLC] and >98% [HPLC]], specific activity: 12-15 GBq/mmol. The partition coefficient was determined [log P=1.63]. A detailed comparative pharmacokinetic study performed for 67Ga cation and [67Ga]-TDMPP. The complex was mostly washed out from the circulation through kidneys. Myocardial uptake was significantly observed by SPECT and biodistribution studies. Knee and shoulder joints demonstrated significant activity uptake in 2h post injection. Higher water solubility of the complex due to ionic nature of the complex is an advantage for rapid wash-out of the complex from the system, the complex has significant joint uptake compared to other radiolabeled porphyrins which the mechanisms are explained

Preparation and quality control of scandium-46 bleomycin as a possible therapeutic agent

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

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]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

Preparation and biodistribution studies of a radiogallium-acetylacetonatebis [thiosemicarbazone] complex in tumor-bearing rodents

Various radiometal complexes have been developed for tumor imaging, especially Ga-68 tracer. In the present study, the development of a radiogallium bis-thiosemicarbazone complex has been reported. [[67]Ga] acetylacetonate bis[thiosemicarbazone] complex [[[67]Ga] AATS] was prepared starting [[67]Ga]Gallium acetate and freshly prepared acetylacetonate bis [thiosemicarbazone] [AATS] in 30 min at 90°C. The partition co-efficient and the stability of the tracer were determined in final solution [25°C] and the presence of human serum [37°C] up to 24 h. The biodistribution of the labeled compound in wild-type and fibrosarcoma-bearing rodents were determined up to 72 h. The radiolabled Ga complex was prepared in high radiochemical purity [> 97%, HPLC] followed by initial biodistribution data with the significant tumor accumulation of the tracer in 2 h which is far higher than free Ga-67 cation while the compound wash-out is significantly faster. Above-mentioned pharmacokinetic properties suggest an interesting radiogallium complex while prepared by the PET Ga radioisotope, 68Ga, in accordance with the physical half life, for use in fibrosarcoma tumors, and possibly other malignancies

Indium-111 maltolate complex as a cell labeling agent for SPECT imaging

Due to the cell labeling potentials of various metal-maltol complexes, the idea of developing a possible cell labeling imaging agent using single photon emission computed chromatography [SPECT] with [[m]ln]-maltolate complex has been investigated. [[IH]In] labeled 3-hydroxy-2-methyl-4H-pyran-4-onate [[m]In]-maltolate] was prepared using freshly prepared [[IH]In]InCl[3] and 3-hydroxy-2-methyl-4H-pyran-4-onate in a sodium salt form in 25 min at 45°C. Stability of the complex was checked in final formulation and human serum for 48 h. The partition coefficient was calculated for the compound followed by biodistribution and imaging studies. [[IU]In]-maltolate was successively used in the radiolabeling of red blood cells for diagnostic studies. The complex was prepared successfully [radiochemical purity: >98% ITLC, >98% HPLC specific activity: 15-17 GBq/mmol, log P=0.278]. The complex is mostly washed out from the circulation through kidneys in 24h. the cell labeling efficacy was significant at the time of experiment. [[In]ln]-maltolate can be an interesting cell imaging agent, due to stability and cell avidity of metal maltol complexes, however, further biodistribution studies in various cells as well as diagnostic protocols is necessary

Development of Ga-67 maltolate complex as an imaging agent

Due to the antitumor activity of Gallium MAL complex, as well as recent findings on new targeted biomolecules in malignant cells through this complex, the development of radiolabeled gallium complex for future imaging studies was targeted. Ga-67 labeled 3-hydroxy-2-methyl-4H-pyran-4-onate [Ga-67 MAL] was prepared using freshly prepared Ga-67 chloride and 3-hydroxy-2-methyl-4H-pyran-4-onate in a sodium salt form in 25 min at 40°C. The stability of the complex was checked in final formulation and human serum for 24 h followed by the administration in Swiss mice for biodistribution studies. The complex was prepared in high radiochemical purity [> 97% ITLC, > 98% HPLC] and specific activity of 13-14 GBq/mmol and was stable in the presence of serum for 48 h. The partition coefficient was calculated for the compound [log;? = 0.40]. A detailed comparative pharmacokinetic study was performed for Ga-67 cation and Ga-67-MAL. The complex is more rapidly washed out from the circulation through kidneys and liver compared to Ga-67 cation and can be an interesting tumor imaging agent due to the fact that the cold compound is undergoing clinical trials as a safe and potential therapeutic agent for cancer

[Construction of pcDNA3.1+ vector containing FMDV type O/IRN/1/2007-VP1 gene, confirmation of protein expression in BHKT7 cells and evaluation of immune response in mice model]

The aim of this study was to construct a pcDNA3.1+vector containing FMDV type O/IRN/1/2007-VP1 gene, protein expression in BHKT7 cells and evaluation of immune response in BALB/c mice. FMDV type O/IRN/1/2007 was isolated from a cattle in Ray in 2007 and serotyped. The purified VP1 gene was sub-cloned into the PTZ57R/T vector and pcDNA3.1+expression vector. The PCR product of Vp1 gene without stop codon was sub-cloned upstream of EGFP gene into the pEGFP-N1 vector to evaluate VP1-GFP fusion protein expression. The pcDNA3.1-VP1 and pEGFP-VP1 vectors were transfected into BHKT7 cell line. The expression of VP1 protein was evaluated by SDS-PAGE, western blotting and florescent analysis of VP1-GFP fusion protein. The mice were injected subcutaneously by pcDNA3.1-VP1 vector as DNA vaccine and titration of neutralizing antiserum and T cell proliferation assay were done to evaluate the immune response. Insertion of VP1 gene was confirmed by double digestion of sub-cloned PTZ57R/T, pcDNA3.1+and pEGFP-N1 vectors. The specific band in western blotting was also confirmed the VP1 protein expression in BHKT7 cells. The expression of VP1-GFP fusion protein was observed under the immune-florescent inverted microscopy as more green florescent spots versus expression of GFP protein, alone. The neutralizing antiserum titer and T cell proliferation increased significantly in the group of mice vaccinated with pcDNA3.1+-VP1 vector verses control groups [P<0.05]. The results showed that the target gene was amplified, cloned in the cloning and expression vectors and protein expression was confirmed successfully. According to the confirmed VP1 protein expression and increasing neutralizing antiserum titer and T cell proliferation by pcDNA3.1+-VP1 vector [P<0.05], it can be used as DNA vaccine against FMDV type O/IRN/2007

Production of holmium-166 DOTMP: a promising agent for bone marrow ablation in hematologic malignancies

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

Radiosynthesis and biological evaluation of [111]in-tris [8-hydroxy-2-methylquinoline] complex as a possible imaging agent

Due to the interesting pharmacological properties of radiolabeled metal oxine derivatives such as cell internalization, tumor avidity and antiproteosome activity, [111]In-tris[8-Hydroxy-2-methylquinoline] [[111]In-HMQ] was developed in this study. [111]In-HMQ was prepared using [111]InCl[3] and 8-Hydroxy-2-methylquinoline [HMQ] for 60 min at 100[degree sign] C [radiochemical purity: >99% ITLC, >99% HPLC, specific activity: 13-14 GBq/mmol]. Stability of the complex was checked in final formulation and in the presence of human serum for 48 h. The partition coefficient was calculated for the compound [log P=0.68]. The biodistribution of the labeled compound in vital organs of wild-type rats was studied using scarification studies and SPECT up to 24 h. A detailed comparative pharmacokinetic study for [111] In cation and [111]In-HMQ are performed up to 24h. The complex is mostly cleaned from the circulation by kidneys and is a compound rapidly washing from the circulation. The biodistribution of the complex in tumor models is on-going

Preparation and biodistribution study of [67]Ga-gallium calcitonin

In order to develop a radiolabeled calcitonin [CT] derivative for receptor imaging studies, CT was successively labeled with [67]G-gallium chloride. The best results of the conjugation were obtained by the addition of 0.5 ml of a CT nasal pharmaceutical solution [1100 IU] to a glass tube pre-coated with DTPA-dianhydride [0.01 mg] at 25 [degree sign] with continuous mild stirring for 30 min. after solid phase purification of the radiolabeled hormone, instant thin layer chromatography [ITLC] showed radiochemical purity of higher than 95% at optimized conditions [specific activity = 67-134 KBq/IU, labeling efficiency 70%]. [67]Ga-DTPA-CT mainly accumulates in the liver. Preliminary in vivo studies [ID/g%] in male wild-type rats showed significant liver uptake of the tracer after 24 hours. [67]Ga-DTPA-CT can be a suitable probe for biodistribution study of CT receptors in various physiological as well as neoplastic lesions with over-expressed calcitonin receptors

Preliminary imaging studies of [[61]Cu] diacetyl-bis [N[4]-methylthiosemi-carbazone] in normal and hypoxic tumor models

[[61]Cu] diacetyl-bis [N[4] -methylthiosemicarbazone] [[[61]Cu] ATSM] is a well-established hypoxia imaging tracer with simple production and significant specifity. In this work the accumulation of the tracer is studied in wild-type, necrotic and hypoxic fibrosarcoma tumors. [[61] Cu] ATSM was prepared using ATSM ligand and [[61]Cu] CuOAc followed by i.v. administration and imaging studies in wid-type rats and hypoxic fibrosarcoma-bearing mic.e [[61] Cu] ATSM with high radiochemical purity [>99%, HPLC, RTLC] was injected to wild-type rats as well as hypoxic and necrotic fibrosarcoma-bearing mice followed by imaging up to 3 hours. [[61] Cu] ATSM was mainly accumulated in liver, as well as kidney and bladder and less but still significant in brain of wild-type rats. A significant and hypoxia-specific tumor/non tumor ratio in hypoxic models was observed by co-incidence imaging 2h post inection, while in necrotic and 12-week tumor-induced mice very slight tumor uptakes were detected. [[61]Cu] ATSM is a positron emission tomography [PET] radiotracer for selective tumor hypoxia imaging from necrotic and proliferative tumors

Development of sm-153 chitosan for radiosynovectomy

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

[Possibility of production of a novel radiopharmaceutical for identification of hypoxic tissues]

Hypoxia is an important determinant for biological behavior of malignant solid tumors. In vitro and in vivo studies have shown that tumor hypoxia is associated with an increased likelihood of local recurrence and distant metastasis, as well as resistance to radiation therapy and certain types of chemotherapy. Studies have shown that some copper-bis thiosemicarbazones especially, Cu-ATSM accumulates avidly in hypoxic cells, but washes out rapidly from normoxic cell. [[61]Cu]-diacetyl-bis [N4-methylthiosemicarbazone] [[61]Cu]-ATSM] was prepared using house-made ATSM ligand and [[61]Cu]CuCl[2] produced via the [nat]Zn[p,x] [61]Cu [180[1/4]A proton irradiation, 22MeV, 3.2h] and purified by ion chromatography method. [[61]Cu]-ATSM was administered into normal and tumor bearing rodents up to 180 minutes followed by biodistribution and co-incidence imaging studies. Radionuclidic control showed the presence of 67.41[4.23%], 282.96[12.2%], 373[2.15%], 511[122.9%], 656[10.77%], 1186[3.75%] keV-rays from [61]Cu and showed a radionuclidic purity higher than 99%. The rest of activity was attributed to [61]Cu [0.23%]. [[61]Cu]-ATSM radiochemical purity was >99% shown by HPLC and RTLC methods. A significant difference was observed between tumor and non tumor accumulation. The method used in this research for the production and chemical separation of 61Cu was simple and cost effective. [[61]Cu]-ATSM is PET radiopharmaceutical for hypoxia imaging with an intermediate half life, and our experiments on this radiopharmaceutical have shown satisfactory results, suitable for future PET studies in human

Production and quality control of [166]Ho-chitosan for therapeutic applications

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