Hassan Yousefnia - Academia.edu (original) (raw)
Papers by Hassan Yousefnia
Nukleonika, 2009
According to our previous works on the radiosynthesis and evaluation of non-fluorine PET radiopha... more According to our previous works on the radiosynthesis and evaluation of non-fluorine PET radiopharmaceuticals [5, 13], we have been interested in the production and application of Cu-61 tumor seeking radiopharmaceuticals [6]. 61 Cu is a positron emitter (t 1/2 = 3.33 h, β + : 62%, EC: 38%), with excellent potentials for application in PET method and molecular imaging. Few production methods of copper-61 have been reported for radiolabeling of biomolecules and other applications [9, 10] leading to the development of small molecules [3, 8] for various diagnostic purposes. Copper oxinate complex is considered an antineoplastic compound with various mechanisms. Some reports demonstrate anti-proteasome and apoptosis inducing properties for this molecule [1]. These interesting biological activities are not reported for free copper cation as well as oxine ligand by any research group independently. Studies concerning the anti-proteasome activity demonstrated that the Cu-oxinate complex forms an unknown complex with proteasome and, finally, quinoline moiety of the complex inactivates the proteasome by an oxido-redox mechanism. Such a mechanism has
Frontiers in biomedical technologies, Dec 30, 2018
Purpose: 68 Ga is a generator-based radionuclide with suitable characteristics for PET imaging. 6... more Purpose: 68 Ga is a generator-based radionuclide with suitable characteristics for PET imaging. 68 Ga-EDTMP has recently been introduced as a new agent for bone imaging. In this study, the human absorbed dose of this agent was calculated according to RADAR method and based on the bio-distribution data in Wild-type rats. Materials and Methods: 68 Ga was obtained from 68 Ge/ 68 Ga generator. While, the radiolabeled complex was prepared in the optimized conditions, the radiochemical purity was checked by Instant Thin Layer Chromatography (ITLC) method. Absorbed dose of each human organ was calculated following the biodistribution assessment of the complex in the Wild-type rats up to 120 min. Results: 68 Ga was prepared with radionuclidic purity and radiochemical purity of higher than 99%. The results indicated the radiochemical purity of higher than 99% for 68 Ga-EDTMP. As expected, bone surface and bone marrow with 0.112 and 0.053 mSv/MBq, respectively, received the highest absorbed dose. The dose of total body was estimated to be 0.006 mSv/MBq. Conclusion: according to the results, the radiolabeled complex can be considered as a safe agent for bone imaging.
International Journal of Radiation Research
Bone metastases are observed in a wide range of cancers leading to intolerable pain. While early ... more Bone metastases are observed in a wide range of cancers leading to intolerable pain. While early detection can help the physicians in the decision of the type of treatment, various radiopharmaceuticals using phosphonates like <sup>68</sup>Ga-EDTMP have been developed. In this work, due to the importance of absorbed dose, human absorbed dose of this new agent was calculated for the first time based on biodistribution data in Wild-type rats. <sup>68</sup>Ga was obtained from <sup>68</sup>Ge/<sup>68</sup>Ga generator with radionuclidic purity and radiochemical purity of higher than 99%. The radiolabeled complex was prepared in the optimized conditions. Radiochemical purity of the radiolabeled complex was checked by instant thin layer chromatography (ITLC) method using Whatman No. 2 paper and saline. The results indicated the radiochemical purity of higher than 99%. The radiolabelled complex was injected into the Wild-type rats and its bio...
Iranian Journal of Basic Medical Sciences, 2013
Objective(s): In this study, 166Ho-1,2-propylene di-amino tetra(methy1enephosphonicAcid) (166Ho-P... more 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.
Asia Oceania Journal of Nuclear Medicine and Biology, 2018
Objective(s): Studies have indicated advantageous properties of [DOTA-DPhe1, Tyr3] octreotide (DO... more Objective(s): Studies have indicated advantageous properties of [DOTA-DPhe1, Tyr3] octreotide (DOTATOC) in tumor models and labeling with gallium. Breast cancer is the second leading cause of cancer mortality in women, and most of these cancers are often an adenocarcinoma. Due to the importance of target to non-target ratios in the efficacy of diagnosis, the pharmacokinetic of 68Ga-DOTATOC in an adenocarcinoma breast cancer animal model was studied in this research, and the optimized time for imaging was determined. Methods: 68Ga was obtained from 68Ge/68Ga generator. The complex was prepared at optimized conditions. Radiochemical purity of the complex was checked using both HPLC and ITLC methods. Biodistribution of the complex was studied in BALB/c mice bearing adenocarcinoma breast cancer. Also, PET/CT imaging was performed up to 120 min post injection. Results: The complex was produced with radiochemical purity of greater than 98% and specific activity of about 40 GBq/mM at optim...
Asia Oceania journal of nuclear medicine & biology, 2015
Objective(s): Recently, bone-avid radiopharmaceuticals have been shown to have potential benefits... more 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 ...
![Research paper thumbnail of Pharmacokinetic studies and human absorbed dose estimation of 68Ga-(4 {[(bis (phosphonomethyl)) carbamoyl] methyl}-7,10-bis(carboxymethy l) -1,4,7,10-tetraazacyclododec-1-yl) acetic acid](https://attachments.academia-assets.com/119752473/thumbnails/1.jpg)
](Iranian Journal of Radiation Research, 2018
Background: In this study, human absorbed dose of a newly introduced bone imaging agent, 68Ga-(4-... more Background: In this study, human absorbed dose of a newly introduced bone imaging agent, 68Ga-(4-{[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis (carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl) acetic acid (68Ga-BPAMD), was estimated based on the rats data. Materials and Methods: Ga was obtained from the Ge/Ga generator and it's radionuclidic and radiochemical purities were investigated. Ga-BPAMD complex was prepared at optimal conditions and the radiochemical purity was studied using instant thin layer chromatography (ITLC) method. The final preparation was injected to the normal rats and the biodistribution of the complex was followed up to 120 min post injection. The accumulated activity for animal organs was calculated. Finally, the human absorbed dose of the complexes was estimated by RADAR method. Results: Ga-BPAMD complex was prepared in high radiochemical purity (>99%, ITLC) at optimal conditions. The biodistribution of the complex demonstrated that the main remai...
Introduction: Recently, due to the special characteristics of Ho and chitosan, Ho-chitosan comple... more Introduction: Recently, due to the special characteristics of Ho and chitosan, Ho-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, Ho-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 ...
Iranian Journal of Pharmaceutical Research : IJPR, 2017
99mTc-Macroaggregated Albumin (99mTc-MAA) has been used as a perfusion agent. This study describe... more 99mTc-Macroaggregated Albumin (99mTc-MAA) has been used as a perfusion agent. This study described development of the 68Ga-MAA via commercially available kits from Pars-Isotopes Company as a 99mTc-MAA kit. 68Ge/68Ga generator was eluted with suprapure HCl (0.6 M, 6 mL) in 0.5 mL fractions. The two fractions with the highest 68GaCl3 activity were generally used for labeling purposes. After labeling, the final product was centrifuged 2 times to purify the solution. Five rats were sacrificed at each exact time interval (from 15 min to 2 h post injection) and the percentage of injected dose per gram (%ID/g) of each organ was measured by direct counting from 11 harvested organs of rats. The RTLC showed that labeling yields before centrifuges were 90% and 95% for Pars-Isotopes and GE kits, respectively and after centrifuges, they became 100%. The microscopic size examination showed a shift in the particle sizes post centrifuges and the biodistribution data revealed the efficiency and bene...
International Journal of Nanomedicine, 2019
Introduction: Nowadays, nanoparticles (NPs) have attracted much attention in biomedical imaging d... more Introduction: Nowadays, nanoparticles (NPs) have attracted much attention in biomedical imaging due to their unique magnetic and optical characteristics. Superparamagnetic iron oxide nanoparticles (SPIONs) are the prosperous group of NPs with the capability to apply as magnetic resonance imaging (MRI) contrast agents. Radiolabeling of targeted SPIONs with positron emitters can develop dual positron emission tomography (PET)/MRI agents to achieve better diagnosis of clinical conditions. Methods: In this work, N,N,N-trimethyl chitosan (TMC)-coated magnetic nanoparticles (MNPs) conjugated to S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (DOTA) as a radioisotope chelator and bombesin (BN) as a targeting peptide (DOTA-BN-TMC-MNPs) were prepared and validated using fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), and powder X-ray diffraction (PXRD) tests. Final NPs were radiolabeled with gallium-68 (68 Ga) and evaluated in vitro and in vivo as a potential PET/MRI probe for breast cancer (BC) detection. Results: The DOTA-BN-TMC-MNPs with a particle size between 20 and 30 nm were efficiently labeled with 68 Ga (radiochemical purity higher than 98% using thin layer chromatography (TLC)). The radiolabeled NPs showed insignificant toxicity (.74% cell viability) and high affinity (IC 50 =8.79 µg/mL) for the gastrin-releasing peptide (GRP)-avid BC T-47D cells using competitive binding assay against 99m Tc-hydrazinonicotinamide (HYNIC)-gamma-aminobutyric acid (GABA)-BN (7-14). PET and MRI showed visible uptake of NPs by T-47D tumors in xenograft mouse models. Conclusion: 68 Ga-DOTA-BN-TMC-MNPs could be a potential diagnostic probe to detect BC using PET/MRI technique.
Asia Oceania journal of nuclear medicine & biology, 2016
Gallium-68 DOTA-DPhe(1)-Tyr(3)-Octreotide ((68)Ga-DOTATOC) has been applied by several European c... more 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. 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 evalua...
Journal of Radioanalytical and Nuclear Chemistry, 2016
The purpose of this study is to evaluate the biodistribution of polyethylene glycol (PEG) coated ... more The purpose of this study is to evaluate the biodistribution of polyethylene glycol (PEG) coated superparamagnetic iron oxide nanoparticles radiolabeled with 68 Ga in normal mice after intravenous administration of this probe. Three mice were sacrificed at specific time intervals. The biodistribution data revealed high uptake by liver and spleen (60.62 and 12.65 %ID/g at 120 min post injection for liver and spleen, respectively). The clearance of other organs was fast. These results suggest that 68 Ga-PEG-SPIONs has magnificent capabilities for applying in (PET-MRI) as a theranostic agent for detection of liver and spleen malignancies.
Malecular Imaging and Radionuclide Therapy, 2015
İterbiyum-175 (İb-175) işaretli pamidronat ve alendronat komplekslerinin kemik ağrısı palyasyonu ... more İterbiyum-175 (İb-175) işaretli pamidronat ve alendronat komplekslerinin kemik ağrısı palyasyonu için etkin ajanlar olarak optimal üretim ve kalite kontrolü sunulmaktadır. Yöntem: İb-175 işaretli pamidronat ve alendronat (175 İb-PMD ve 175 İb-ALN) kompleksleri kabul edilebilir radyokimyasal saflık, stabilite ve anlamlı hidroksiapatit emilimi ile optimize koşullarda başarıyla hazırlandı. Komplekslerin biyodağılımı 48 saate kadar değerlendirildi ve tüm zaman aralıklarında 175 İb-PAM ile anlamlı kemik tutulum oranı saptandı. Aynı zamanda 175 İb-ALN'nin çoğunlukla böbrekler yoluyla ekskrete edildiği tespit edildi. Bulgular: Bir hayvan modelinde, 175 İb-PAM'ın performansı daha önce bildirilen diğer 175 İb-kemiğe bağlanan kompleksler ile eşit ya da daha iyi olarak bulundu. Sonuç: Hesaplamalara göre, 175 İb-ALN'nin için toplam vücut dozu (özellikle böbreklerde) 175 İb-PAM'dan %40 daha yüksektir. Bu durum, 175 İb-PAM'in 175 İb-ALN'den daha güvenli bir alternatif olduğunu öne sürmektedir. Anahtar kelimeler: İb-175, pamidronik asit, alendronik asit, kemik ağrısı palyatif tedavisi, biodağılım, dozimetre Objective: Optimized production and quality control of ytterbium-175 (Yb-175) labeled pamidronate and alendronate complexes as efficient agents for bone pain palliation has been presented. Methods: Yb-175 labeled pamidronate and alendronate (175 Yb-PMD and 175 Yb-ALN) complexes were prepared successfully at optimized conditions with acceptable radiochemical purity, stability and significant hydroxyapatite absorption. The biodistribution of complexes were evaluated up to 48 h, which demonstrated significant bone uptake ratios for 175 Yb-PAM at all-time intervals. It was also detected that 175 Yb-PAM mostly washed out and excreted through the kidneys. Results: The performance of 175 Yb-PAM in an animal model was better or comparable to other 175 Yb-bone seeking complexes previously reported. Conclusion: Based on calculations, the total body dose for 175 Yb-ALN is 40% higher as compared to 175 Yb-PAM (especially kidneys) indicating that 175 Yb-PAM is probably a safer agent than 175 Yb-ALN.
Annals of Nuclear Medicine, 2015
Introduction: Optimized production and quality control of 68 Ga-DOTATATE as an efficient and pref... more Introduction: Optimized production and quality control of 68 Ga-DOTATATE as an efficient and preferable PET radiotracer for somatostatin receptor imaging in neuroendocrine tumors is of great interest. In this study effort has been made to present a fast, efficient, cost-effective and facile protocol for 68 Ga-DOTATATE productions for clinical trials. Methods: 68 Ga-DOTATATEwas prepared using generator-based [ 68 Ga]GaCl 3 and DOTATATE at optimized conditions for time, temperature, ligand amount, gallium content and column cartridge purification followed by proper formulation. The biodistribution of the tracer in rats was studied using tissue counting and PET/CT imaging up to 120 min. Results: 68 Ga-DOTATATE was prepared at optimized conditions in 7-10 min at 95C followed by SPE using C 18 cartridge (radiochemical purity99±0.88% ITLC, >99% HPLC, specific activity: 1200-1850 MBq/nM). The biodistribution of the tracer demonstrated high kidney uptake of the tracer in 10-20 min consistent with reported somatostatin receptor mappings. Conclusion: The entire production and quality control of 68Ga-DOTATATE is presented including labeling, purification, HPLC analysis, sterilization and LAL test) took 18-20 min with significant specific activity for administration to limited number of patients in a PET center.
![Research paper thumbnail of Preparation and quality control of ¹⁷⁷Lu-[tris(1,10-phenanthroline) lutetium(III)] complex for therapy](https://attachments.academia-assets.com/119752498/thumbnails/1.jpg)
](Nuclear medicine review. Central & Eastern Europe, 2010
The ¹⁷⁷Lu-[tris(1,10-phenanthroline)lutetium(III)] complex (¹⁷⁷Lu-PQ3) was prepared successfully ... more The ¹⁷⁷Lu-[tris(1,10-phenanthroline)lutetium(III)] complex (¹⁷⁷Lu-PQ3) was prepared successfully with high radiochemical purity (> 99%). Lu-177 chloride was obtained by thermal neutron flux (4 × 10¹³ n.cm⁻².s⁻¹) of natural Lu₂(NO₃)₃ sample, dissolved in acidic media. The radiochemical yield was checked by measuring the radiochemical purity of the (177)Lu-PQ complex by ITLC (10 mM DTPA, pH = 5, as mobile phase). The final complex solution was injected intravenously into wild-type male rats and bio-distribution of the complex was checked for up to 48 hours. The dose limiting organs were shown to be the reticulu-endothelial system. The bio-distribution of the labelled compounds in tumour-bearing animals is under investigation.
Nuclear medicine review. Central & Eastern Europe, 2009
Various radiometal complexes have been developed for tumour imaging, especially Ga-68 tracer. In ... more Various radiometal complexes have been developed for tumour imaging, especially Ga-68 tracer. In this work, the development of a radiogallium bis(thiosemicarbazone) complex has been reported. [(67)Ga]acetylacetonate bis(thio-semicarbazone) complex ([(67)Ga]AATS) was prepared starting with [(67)Ga]Gallium acetate and freshly prepared acetylacetonate bis(thiosemicarbazone) (AATS) for 30 min at 90 degreesC. The partition co-efficient and stability of the tracer was determined in final solution (25 degreesC) and the presence of human serum (37 degreesC) for up to 24 hours. The biodistribution of the labelled compound in wild-type and fibrosarcoma-bearing rodents were determined for up to 72 hours. The radiolabelled Ga complex was prepared to a high radiochemical purity (> 97%, HPLC) followed by initial biodistribution data with the significant tumour accumulation of the tracer at two hours, which is far higher than free Ga-67 cation, while the compound wash-out is significantly faste...
![Research paper thumbnail of Evaluation of a [67Ga]-Thiosemicarbazone Complex as Tumor Imaging Agent](https://attachments.academia-assets.com/119752491/thumbnails/1.jpg)
](Scientia Pharmaceutica, 2009
[ 67 Ga]labeled 2-acetylpyridine 4,4-dimethylthiosemicarbazone ([ 67 Ga]-[APTSM 2 ] 2 +) was prep... more [ 67 Ga]labeled 2-acetylpyridine 4,4-dimethylthiosemicarbazone ([ 67 Ga]-[APTSM 2 ] 2 +) was prepared using freshly prepared [ 67 Ga]GaCl 3 and 2-acetylpyridine 4,4-dimethylthiosemicarbazone (APTSM 2) for 30 min at 90°C (radiochemical purity: >97% ITLC, >98% HPLC, specific activity: 15-20 Ci/mmol). Stability of the complex was checked in human serum for 37°C. The biodistribution of the labeled compound in vital organs of normal and fibrosarcoma bearing mice were compared with that of free Ga 3+ cation up to 24h. Initial SPECT images and biodistribution results showed significant tumor uptake in fibrosarcoma-bearing mice after 2 hour post injection.
![Research paper thumbnail of Preparation and quality control of 177 Lu-[tris (1, 10-phenanthroline) lutetium (III)] complex for therapy](https://attachments.academia-assets.com/119752490/thumbnails/1.jpg)
](The 177 Lu-[tris(1,10-phenanthroline)lutetium(III)] complex (177 Lu-PQ3) was prepared successfull... more The 177 Lu-[tris(1,10-phenanthroline)lutetium(III)] complex (177 Lu-PQ3) was prepared successfully with high radiochemical purity (> 99%). Lu-177 chloride was obtained by thermal neutron flux (4 × 10 13 n.cm-2 .s-1) of natural Lu 2 (NO 3) 3 sample, dissolved in acidic media. The radiochemical yield was checked by measuring the radiochemical purity of the 177 Lu-PQ complex by ITLC (10 mM DTPA, pH = 5, as mobile phase). The final complex solution was injected intravenously into wild-type male rats and bio-distribution of the complex was checked for up to 48 hours. The dose limiting organs were shown to be the reticulu-endothelial system. The bio-distribution of the labelled compounds in tumour-bearing animals is under investigation.
Introduction: In this research, [ 166 Ho]Holmium chitosan complex production is described in deta... more Introduction: 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. Methods: 166 Ho-chitosan complex was prepared using chitosan concentrations and 166 HoCl 3 followed by intraarticular injection and biodistribution studies in wild-type rats including and excluding injected knee. Results: 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. Conclusion: 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.
Nukleonika, 2009
According to our previous works on the radiosynthesis and evaluation of non-fluorine PET radiopha... more According to our previous works on the radiosynthesis and evaluation of non-fluorine PET radiopharmaceuticals [5, 13], we have been interested in the production and application of Cu-61 tumor seeking radiopharmaceuticals [6]. 61 Cu is a positron emitter (t 1/2 = 3.33 h, β + : 62%, EC: 38%), with excellent potentials for application in PET method and molecular imaging. Few production methods of copper-61 have been reported for radiolabeling of biomolecules and other applications [9, 10] leading to the development of small molecules [3, 8] for various diagnostic purposes. Copper oxinate complex is considered an antineoplastic compound with various mechanisms. Some reports demonstrate anti-proteasome and apoptosis inducing properties for this molecule [1]. These interesting biological activities are not reported for free copper cation as well as oxine ligand by any research group independently. Studies concerning the anti-proteasome activity demonstrated that the Cu-oxinate complex forms an unknown complex with proteasome and, finally, quinoline moiety of the complex inactivates the proteasome by an oxido-redox mechanism. Such a mechanism has
Frontiers in biomedical technologies, Dec 30, 2018
Purpose: 68 Ga is a generator-based radionuclide with suitable characteristics for PET imaging. 6... more Purpose: 68 Ga is a generator-based radionuclide with suitable characteristics for PET imaging. 68 Ga-EDTMP has recently been introduced as a new agent for bone imaging. In this study, the human absorbed dose of this agent was calculated according to RADAR method and based on the bio-distribution data in Wild-type rats. Materials and Methods: 68 Ga was obtained from 68 Ge/ 68 Ga generator. While, the radiolabeled complex was prepared in the optimized conditions, the radiochemical purity was checked by Instant Thin Layer Chromatography (ITLC) method. Absorbed dose of each human organ was calculated following the biodistribution assessment of the complex in the Wild-type rats up to 120 min. Results: 68 Ga was prepared with radionuclidic purity and radiochemical purity of higher than 99%. The results indicated the radiochemical purity of higher than 99% for 68 Ga-EDTMP. As expected, bone surface and bone marrow with 0.112 and 0.053 mSv/MBq, respectively, received the highest absorbed dose. The dose of total body was estimated to be 0.006 mSv/MBq. Conclusion: according to the results, the radiolabeled complex can be considered as a safe agent for bone imaging.
International Journal of Radiation Research
Bone metastases are observed in a wide range of cancers leading to intolerable pain. While early ... more Bone metastases are observed in a wide range of cancers leading to intolerable pain. While early detection can help the physicians in the decision of the type of treatment, various radiopharmaceuticals using phosphonates like <sup>68</sup>Ga-EDTMP have been developed. In this work, due to the importance of absorbed dose, human absorbed dose of this new agent was calculated for the first time based on biodistribution data in Wild-type rats. <sup>68</sup>Ga was obtained from <sup>68</sup>Ge/<sup>68</sup>Ga generator with radionuclidic purity and radiochemical purity of higher than 99%. The radiolabeled complex was prepared in the optimized conditions. Radiochemical purity of the radiolabeled complex was checked by instant thin layer chromatography (ITLC) method using Whatman No. 2 paper and saline. The results indicated the radiochemical purity of higher than 99%. The radiolabelled complex was injected into the Wild-type rats and its bio...
Iranian Journal of Basic Medical Sciences, 2013
Objective(s): In this study, 166Ho-1,2-propylene di-amino tetra(methy1enephosphonicAcid) (166Ho-P... more 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.
Asia Oceania Journal of Nuclear Medicine and Biology, 2018
Objective(s): Studies have indicated advantageous properties of [DOTA-DPhe1, Tyr3] octreotide (DO... more Objective(s): Studies have indicated advantageous properties of [DOTA-DPhe1, Tyr3] octreotide (DOTATOC) in tumor models and labeling with gallium. Breast cancer is the second leading cause of cancer mortality in women, and most of these cancers are often an adenocarcinoma. Due to the importance of target to non-target ratios in the efficacy of diagnosis, the pharmacokinetic of 68Ga-DOTATOC in an adenocarcinoma breast cancer animal model was studied in this research, and the optimized time for imaging was determined. Methods: 68Ga was obtained from 68Ge/68Ga generator. The complex was prepared at optimized conditions. Radiochemical purity of the complex was checked using both HPLC and ITLC methods. Biodistribution of the complex was studied in BALB/c mice bearing adenocarcinoma breast cancer. Also, PET/CT imaging was performed up to 120 min post injection. Results: The complex was produced with radiochemical purity of greater than 98% and specific activity of about 40 GBq/mM at optim...
Asia Oceania journal of nuclear medicine & biology, 2015
Objective(s): Recently, bone-avid radiopharmaceuticals have been shown to have potential benefits... more 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 ...
Iranian Journal of Radiation Research, 2018
Background: In this study, human absorbed dose of a newly introduced bone imaging agent, 68Ga-(4-... more Background: In this study, human absorbed dose of a newly introduced bone imaging agent, 68Ga-(4-{[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis (carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl) acetic acid (68Ga-BPAMD), was estimated based on the rats data. Materials and Methods: Ga was obtained from the Ge/Ga generator and it's radionuclidic and radiochemical purities were investigated. Ga-BPAMD complex was prepared at optimal conditions and the radiochemical purity was studied using instant thin layer chromatography (ITLC) method. The final preparation was injected to the normal rats and the biodistribution of the complex was followed up to 120 min post injection. The accumulated activity for animal organs was calculated. Finally, the human absorbed dose of the complexes was estimated by RADAR method. Results: Ga-BPAMD complex was prepared in high radiochemical purity (>99%, ITLC) at optimal conditions. The biodistribution of the complex demonstrated that the main remai...
Introduction: Recently, due to the special characteristics of Ho and chitosan, Ho-chitosan comple... more Introduction: Recently, due to the special characteristics of Ho and chitosan, Ho-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, Ho-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 ...
Iranian Journal of Pharmaceutical Research : IJPR, 2017
99mTc-Macroaggregated Albumin (99mTc-MAA) has been used as a perfusion agent. This study describe... more 99mTc-Macroaggregated Albumin (99mTc-MAA) has been used as a perfusion agent. This study described development of the 68Ga-MAA via commercially available kits from Pars-Isotopes Company as a 99mTc-MAA kit. 68Ge/68Ga generator was eluted with suprapure HCl (0.6 M, 6 mL) in 0.5 mL fractions. The two fractions with the highest 68GaCl3 activity were generally used for labeling purposes. After labeling, the final product was centrifuged 2 times to purify the solution. Five rats were sacrificed at each exact time interval (from 15 min to 2 h post injection) and the percentage of injected dose per gram (%ID/g) of each organ was measured by direct counting from 11 harvested organs of rats. The RTLC showed that labeling yields before centrifuges were 90% and 95% for Pars-Isotopes and GE kits, respectively and after centrifuges, they became 100%. The microscopic size examination showed a shift in the particle sizes post centrifuges and the biodistribution data revealed the efficiency and bene...
International Journal of Nanomedicine, 2019
Introduction: Nowadays, nanoparticles (NPs) have attracted much attention in biomedical imaging d... more Introduction: Nowadays, nanoparticles (NPs) have attracted much attention in biomedical imaging due to their unique magnetic and optical characteristics. Superparamagnetic iron oxide nanoparticles (SPIONs) are the prosperous group of NPs with the capability to apply as magnetic resonance imaging (MRI) contrast agents. Radiolabeling of targeted SPIONs with positron emitters can develop dual positron emission tomography (PET)/MRI agents to achieve better diagnosis of clinical conditions. Methods: In this work, N,N,N-trimethyl chitosan (TMC)-coated magnetic nanoparticles (MNPs) conjugated to S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (DOTA) as a radioisotope chelator and bombesin (BN) as a targeting peptide (DOTA-BN-TMC-MNPs) were prepared and validated using fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), and powder X-ray diffraction (PXRD) tests. Final NPs were radiolabeled with gallium-68 (68 Ga) and evaluated in vitro and in vivo as a potential PET/MRI probe for breast cancer (BC) detection. Results: The DOTA-BN-TMC-MNPs with a particle size between 20 and 30 nm were efficiently labeled with 68 Ga (radiochemical purity higher than 98% using thin layer chromatography (TLC)). The radiolabeled NPs showed insignificant toxicity (.74% cell viability) and high affinity (IC 50 =8.79 µg/mL) for the gastrin-releasing peptide (GRP)-avid BC T-47D cells using competitive binding assay against 99m Tc-hydrazinonicotinamide (HYNIC)-gamma-aminobutyric acid (GABA)-BN (7-14). PET and MRI showed visible uptake of NPs by T-47D tumors in xenograft mouse models. Conclusion: 68 Ga-DOTA-BN-TMC-MNPs could be a potential diagnostic probe to detect BC using PET/MRI technique.
Asia Oceania journal of nuclear medicine & biology, 2016
Gallium-68 DOTA-DPhe(1)-Tyr(3)-Octreotide ((68)Ga-DOTATOC) has been applied by several European c... more 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. 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 evalua...
Journal of Radioanalytical and Nuclear Chemistry, 2016
The purpose of this study is to evaluate the biodistribution of polyethylene glycol (PEG) coated ... more The purpose of this study is to evaluate the biodistribution of polyethylene glycol (PEG) coated superparamagnetic iron oxide nanoparticles radiolabeled with 68 Ga in normal mice after intravenous administration of this probe. Three mice were sacrificed at specific time intervals. The biodistribution data revealed high uptake by liver and spleen (60.62 and 12.65 %ID/g at 120 min post injection for liver and spleen, respectively). The clearance of other organs was fast. These results suggest that 68 Ga-PEG-SPIONs has magnificent capabilities for applying in (PET-MRI) as a theranostic agent for detection of liver and spleen malignancies.
Malecular Imaging and Radionuclide Therapy, 2015
İterbiyum-175 (İb-175) işaretli pamidronat ve alendronat komplekslerinin kemik ağrısı palyasyonu ... more İterbiyum-175 (İb-175) işaretli pamidronat ve alendronat komplekslerinin kemik ağrısı palyasyonu için etkin ajanlar olarak optimal üretim ve kalite kontrolü sunulmaktadır. Yöntem: İb-175 işaretli pamidronat ve alendronat (175 İb-PMD ve 175 İb-ALN) kompleksleri kabul edilebilir radyokimyasal saflık, stabilite ve anlamlı hidroksiapatit emilimi ile optimize koşullarda başarıyla hazırlandı. Komplekslerin biyodağılımı 48 saate kadar değerlendirildi ve tüm zaman aralıklarında 175 İb-PAM ile anlamlı kemik tutulum oranı saptandı. Aynı zamanda 175 İb-ALN'nin çoğunlukla böbrekler yoluyla ekskrete edildiği tespit edildi. Bulgular: Bir hayvan modelinde, 175 İb-PAM'ın performansı daha önce bildirilen diğer 175 İb-kemiğe bağlanan kompleksler ile eşit ya da daha iyi olarak bulundu. Sonuç: Hesaplamalara göre, 175 İb-ALN'nin için toplam vücut dozu (özellikle böbreklerde) 175 İb-PAM'dan %40 daha yüksektir. Bu durum, 175 İb-PAM'in 175 İb-ALN'den daha güvenli bir alternatif olduğunu öne sürmektedir. Anahtar kelimeler: İb-175, pamidronik asit, alendronik asit, kemik ağrısı palyatif tedavisi, biodağılım, dozimetre Objective: Optimized production and quality control of ytterbium-175 (Yb-175) labeled pamidronate and alendronate complexes as efficient agents for bone pain palliation has been presented. Methods: Yb-175 labeled pamidronate and alendronate (175 Yb-PMD and 175 Yb-ALN) complexes were prepared successfully at optimized conditions with acceptable radiochemical purity, stability and significant hydroxyapatite absorption. The biodistribution of complexes were evaluated up to 48 h, which demonstrated significant bone uptake ratios for 175 Yb-PAM at all-time intervals. It was also detected that 175 Yb-PAM mostly washed out and excreted through the kidneys. Results: The performance of 175 Yb-PAM in an animal model was better or comparable to other 175 Yb-bone seeking complexes previously reported. Conclusion: Based on calculations, the total body dose for 175 Yb-ALN is 40% higher as compared to 175 Yb-PAM (especially kidneys) indicating that 175 Yb-PAM is probably a safer agent than 175 Yb-ALN.
Annals of Nuclear Medicine, 2015
Introduction: Optimized production and quality control of 68 Ga-DOTATATE as an efficient and pref... more Introduction: Optimized production and quality control of 68 Ga-DOTATATE as an efficient and preferable PET radiotracer for somatostatin receptor imaging in neuroendocrine tumors is of great interest. In this study effort has been made to present a fast, efficient, cost-effective and facile protocol for 68 Ga-DOTATATE productions for clinical trials. Methods: 68 Ga-DOTATATEwas prepared using generator-based [ 68 Ga]GaCl 3 and DOTATATE at optimized conditions for time, temperature, ligand amount, gallium content and column cartridge purification followed by proper formulation. The biodistribution of the tracer in rats was studied using tissue counting and PET/CT imaging up to 120 min. Results: 68 Ga-DOTATATE was prepared at optimized conditions in 7-10 min at 95C followed by SPE using C 18 cartridge (radiochemical purity99±0.88% ITLC, >99% HPLC, specific activity: 1200-1850 MBq/nM). The biodistribution of the tracer demonstrated high kidney uptake of the tracer in 10-20 min consistent with reported somatostatin receptor mappings. Conclusion: The entire production and quality control of 68Ga-DOTATATE is presented including labeling, purification, HPLC analysis, sterilization and LAL test) took 18-20 min with significant specific activity for administration to limited number of patients in a PET center.
Nuclear medicine review. Central & Eastern Europe, 2010
The ¹⁷⁷Lu-[tris(1,10-phenanthroline)lutetium(III)] complex (¹⁷⁷Lu-PQ3) was prepared successfully ... more The ¹⁷⁷Lu-[tris(1,10-phenanthroline)lutetium(III)] complex (¹⁷⁷Lu-PQ3) was prepared successfully with high radiochemical purity (> 99%). Lu-177 chloride was obtained by thermal neutron flux (4 × 10¹³ n.cm⁻².s⁻¹) of natural Lu₂(NO₃)₃ sample, dissolved in acidic media. The radiochemical yield was checked by measuring the radiochemical purity of the (177)Lu-PQ complex by ITLC (10 mM DTPA, pH = 5, as mobile phase). The final complex solution was injected intravenously into wild-type male rats and bio-distribution of the complex was checked for up to 48 hours. The dose limiting organs were shown to be the reticulu-endothelial system. The bio-distribution of the labelled compounds in tumour-bearing animals is under investigation.
Nuclear medicine review. Central & Eastern Europe, 2009
Various radiometal complexes have been developed for tumour imaging, especially Ga-68 tracer. In ... more Various radiometal complexes have been developed for tumour imaging, especially Ga-68 tracer. In this work, the development of a radiogallium bis(thiosemicarbazone) complex has been reported. [(67)Ga]acetylacetonate bis(thio-semicarbazone) complex ([(67)Ga]AATS) was prepared starting with [(67)Ga]Gallium acetate and freshly prepared acetylacetonate bis(thiosemicarbazone) (AATS) for 30 min at 90 degreesC. The partition co-efficient and stability of the tracer was determined in final solution (25 degreesC) and the presence of human serum (37 degreesC) for up to 24 hours. The biodistribution of the labelled compound in wild-type and fibrosarcoma-bearing rodents were determined for up to 72 hours. The radiolabelled Ga complex was prepared to a high radiochemical purity (> 97%, HPLC) followed by initial biodistribution data with the significant tumour accumulation of the tracer at two hours, which is far higher than free Ga-67 cation, while the compound wash-out is significantly faste...
Scientia Pharmaceutica, 2009
[ 67 Ga]labeled 2-acetylpyridine 4,4-dimethylthiosemicarbazone ([ 67 Ga]-[APTSM 2 ] 2 +) was prep... more [ 67 Ga]labeled 2-acetylpyridine 4,4-dimethylthiosemicarbazone ([ 67 Ga]-[APTSM 2 ] 2 +) was prepared using freshly prepared [ 67 Ga]GaCl 3 and 2-acetylpyridine 4,4-dimethylthiosemicarbazone (APTSM 2) for 30 min at 90°C (radiochemical purity: >97% ITLC, >98% HPLC, specific activity: 15-20 Ci/mmol). Stability of the complex was checked in human serum for 37°C. The biodistribution of the labeled compound in vital organs of normal and fibrosarcoma bearing mice were compared with that of free Ga 3+ cation up to 24h. Initial SPECT images and biodistribution results showed significant tumor uptake in fibrosarcoma-bearing mice after 2 hour post injection.
The 177 Lu-[tris(1,10-phenanthroline)lutetium(III)] complex (177 Lu-PQ3) was prepared successfull... more The 177 Lu-[tris(1,10-phenanthroline)lutetium(III)] complex (177 Lu-PQ3) was prepared successfully with high radiochemical purity (> 99%). Lu-177 chloride was obtained by thermal neutron flux (4 × 10 13 n.cm-2 .s-1) of natural Lu 2 (NO 3) 3 sample, dissolved in acidic media. The radiochemical yield was checked by measuring the radiochemical purity of the 177 Lu-PQ complex by ITLC (10 mM DTPA, pH = 5, as mobile phase). The final complex solution was injected intravenously into wild-type male rats and bio-distribution of the complex was checked for up to 48 hours. The dose limiting organs were shown to be the reticulu-endothelial system. The bio-distribution of the labelled compounds in tumour-bearing animals is under investigation.
Introduction: In this research, [ 166 Ho]Holmium chitosan complex production is described in deta... more Introduction: 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. Methods: 166 Ho-chitosan complex was prepared using chitosan concentrations and 166 HoCl 3 followed by intraarticular injection and biodistribution studies in wild-type rats including and excluding injected knee. Results: 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. Conclusion: 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.