H. Yousefnia

Publications

11 Absorbed Dose Estimation of 68Ga-EDTMP in Human Organs

Authors: H. Yousefnia, S. Zolghadri, A. R. Jalilian

Abstract:

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 68Ga-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. 68Ga was obtained from 68Ge/68Ga 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 biodistribution was studied up to 120 min. As expected, major accumulation was observed in the bone. Absorbed dose of each human organ was calculated based on biodistribution in the rats using RADAR method. Bone surface and bone marrow with 0.112 and 0.053 mSv/MBq, respectively, received the highest absorbed dose. According to these results, the radiolabeled complex is a suitable and safe option for PET bone imaging.

Keywords: rats, absorbed dose, EDTMP

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10 Absorbed Dose Estimation of 177Lu-DOTATOC in Adenocarcinoma Breast Cancer Bearing Mice

Authors: H. Yousefnia, S. Zolghadri, M. Mousavi-Daramoroudi, F. Abbasi-Davani

Abstract:

In this study, the absorbed dose of human organs after injection of 177Lu-DOTATOC was studied based on the biodistribution of the complex in adenocarcinoma breast cancer bearing mice. For this purpose, the biodistribution of the radiolabelled complex was studied and compartmental modeling was applied to calculate the absorbed dose with high precision. As expected, 177Lu-DOTATOC illustrated a notable specific uptake in tumor and pancreas, organs with high level of somatostatin receptor on their surface and the effectiveness of the radio-conjugate for targeting of the breast adenocarcinoma tumors was indicated. The elicited results of modeling were the exponential equations, and those are utilized for obtaining the cumulated activity data by taking their integral. The results also exemplified that non-target absorbed-doses such as the liver, spleen and pancreas were approximately 0.008, 0.004, and 0.039, respectively. While these values were so much lower than target (tumor) absorbed-dose, it seems due to this low toxicity, this complex is a good agent for therapy.

Keywords: Dosimetry, Breast Cancer, compartmental modeling

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9 Time Dependent Biodistribution Modeling of 177Lu-DOTATOC Using Compartmental Analysis

Authors: H. Yousefnia, S. Zolghadri, M. Mousavi-Daramoroudi, F. Abbasi-Davani

Abstract:

In this study, 177Lu-DOTATOC was prepared under optimized conditions (radiochemical purity: > 99%, radionuclidic purity: > 99%). The percentage of injected dose per gram (%ID/g) was calculated for organs up to 168 h post injection. Compartmental model was applied to mathematical description of the drug behaviour in tissue at different times. The biodistribution data showed the significant excretion of the radioactivity from the kidneys. The adrenal and pancreas, as major expression sites for somatostatin receptor (SSTR), had significant uptake. A pharmacokinetic model of 177Lu-DOTATOC was presented by compartmental analysis which demonstrates the behavior of the complex.

Keywords: biodistribution, octreotide, compartmental modeling

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8 Estimation of Human Absorbed Dose Using Compartmental Model

Authors: H. Yousefnia, S. Zolghadri, M. Mousavi-Daramoroudi, F. Abbasi-Davani

Abstract:

Dosimetry is an indispensable and precious factor in patient treatment planning to minimize the absorbed dose in vital tissues. In this study, compartmental model was used in order to estimate the human absorbed dose of 177Lu-DOTATOC from the biodistribution data in wild type rats. For this purpose, 177Lu-DOTATOC was prepared under optimized conditions and its biodistribution was studied in male Syrian rats up to 168 h. Compartmental model was applied to mathematical description of the drug behaviour in tissue at different times. Dosimetric estimation of the complex was performed using radiation absorbed dose assessment resource (RADAR). The biodistribution data showed high accumulation in the adrenal and pancreas as the major expression sites for somatostatin receptor (SSTR). While kidneys as the major route of excretion receive 0.037 mSv/MBq, pancreas and adrenal also obtain 0.039 and 0.028 mSv/MBq. Due to the usage of this method, the points of accumulated activity data were enhanced, and further information of tissues uptake was collected that it will be followed by high (or improved) precision in dosimetric calculations.

Keywords: Syrian rats, compartmental modeling, human absorbed dose

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7 Biodistribution Studies of 177Lu-DOTATOC in Mouse Tumor Model: Possible Utilization in Adenocarcinoma Breast Cancer Treatment

Authors: H. Yousefnia, S. Zolghadri, M. Mousavi-Daramoroudi, F. Abbasi-Davani, S. Kakaei

Abstract:

Despite the appropriate characteristics of 177Lu and DOTATOC, to our best knowledge, the therapeutic benefit of 177Lu-DOTATOC complex in breast cancer has not been reported until now. In this study, biodistribution of 177Lu-DOTA-TOC in mouse tumor model for evaluation of possible utilization of this complex in breast cancer treatment was investigated.177Lu was prepared with the specific activity of 2.6-3 GBq.mg-1 and radionuclidic purity higher than 99%. The radiolabeled complex was prepared in the optimized conditions with the radiochemical purity higher than 99%. The final solution was injected to the BALB/c mice with adenocarcinoma breast cancer. The biodistribution results showed major accumulation in the kidneys as the major excretion route and the somatostatin receptor-positive tissues such as pancreas compared with the other tissues. Also, significant uptake was observed in tumor even in longer time after injection. According to the results obtained in this research study, somatostatin receptors expressed in breast cancers can be targeted with DOTATOC analogues especially with 177Lu-DOTATOC as an ideal therapeutic agent.

Keywords: Breast Cancer, adenocarcinoma, BALB/c mice, DOTATOC

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6 A Green Method for Selective Spectrophotometric Determination of Hafnium(IV) with Aqueous Extract of Ficus carica Tree Leaves

Authors: H. Yousefnia, S. Zolghadri, A. Boveiri Monji, M. Haji Hosseini

Abstract:

A clean spectrophotometric method for the determination of hafnium by using a green reagent, acidic extract of Ficus carica tree leaves is developed. In 6-M hydrochloric acid, hafnium reacts with this reagent to form a yellow product. The formed product shows maximum absorbance at 421 nm with a molar absorptivity value of 0.28 × 104 l mol⁻¹ cm⁻¹, and the method was linear in the 2-11 µg ml⁻¹ concentration range. The detection limit value was found to be 0.312 µg ml⁻¹. Except zirconium and iron, the selectivity was good, and most of the ions did not show any significant spectral interference at concentrations up to several hundred times. The proposed method was green, simple, low cost, and selective.

Keywords: Synthetic Reagents, hafnium, spectrophotometric determination, Ficus carica tree leaves

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5 A Comparison between Reagents Extracted from Tree Leaves for Spectrophotometric Determination of Hafnium(IV)

Authors: H. Yousefnia, S. Zolghadri, A. Boveiri Monji, B. Salimi

Abstract:

The main goal of this paper was to make use of green reagents as a substitute of perilous synthetic reagents and organic solvents for spectrophotometric determination of hafnium(IV). The extracts taken from six different kinds of tree leaves including Acer negundo, Ficus carica, Cerasus avium, Chimonanthus, Salix babylonica and Pinus brutia, were applied as green reagents for the experiments. In 6-M hydrochloric acid, hafnium reacted with the reagent to form a yellow product and showed maximum absorbance at 421 nm. Among tree leaves, Chimonanthus showed satisfactory results with a molar absorptivity value of 0.61 × 104 l mol-1 cm-1 and the method was linear in the 0.3-9 µg mL -1 concentration range. The detection limit value was 0.064 µg mL-1. The proposed method was simple, low cost, clean, and selective.

Keywords: Synthetic Reagents, hafnium, spectrophotometric determination, tree leaves

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4 Human Absorbed Dose Estimation of a New IN-111 Imaging Agent Based on Rat Data

Authors: H. Yousefnia, S. Zolghadri

Abstract:

The measurement of organ radiation exposure dose is one of the most important steps to be taken initially, for developing a new radiopharmaceutical. In this study, the dosimetric studies of a novel agent for SPECT-imaging of the bone metastasis, 111In- 1,4,7,10-tetraazacyclododecane-1,4,7,10 tetraethylene phosphonic acid (111In-DOTMP) complex, have been carried out to estimate the dose in human organs based on the data derived from rats. The radiolabeled complex was prepared with high radiochemical purity in the optimal conditions. Biodistribution studies of the complex was investigated in the male Syrian rats at selected times after injection (2, 4, 24 and 48 h). The human absorbed dose estimation of the complex was made based on data derived from the rats by the radiation absorbed dose assessment resource (RADAR) method. 111In-DOTMP complex was prepared with high radiochemical purity of >99% (ITLC). Total body effective absorbed dose for 111In- DOTMP was 0.061 mSv/MBq. This value is comparable to the other 111In clinically used complexes. The results show that the dose with respect to the critical organs is satisfactory within the acceptable range for diagnostic nuclear medicine procedures. Generally, 111In- DOTMP has interesting characteristics and can be considered as a viable agent for SPECT-imaging of the bone metastasis in the near future.

Keywords: Radar, DOTMP, internal dosimetry, In-111

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3 Preliminary Dosimetric Evaluation of a New Therapeutic 177Lu Complex for Human Based on Biodistribution Data in Rats

Authors: H. Yousefnia, S. Zolghadri, A. Golabi Dezfuli

Abstract:

Abstract—[Tris (1,10-phenanthroline) lanthanum(III)] trithiocyanate is a new compound that has shown high ability for stopping the synthesis of DNA and also acting as a photosensitizer. Nowadays, the radiation dose assessment resource (RADAR) method is known as the most common method for absorbed dose calculation. 177Lu was produced by (n, gamma) reaction in a research reactor. 177Lu-PL3 was prepared in the optimized condition. The radiochemical yield was checked by ITLC method. The biodistribution of the complex was investigated by intravenously injection to wild-type rats via their tail veins. In this study, the absorbed dose of 177Lu-PL3 to human organs was estimated by RADAR method. 177Lu was prepared with a specific activity of 2.6-3 GBq.mg-1 and radionuclide purity of 99.98 %. Final preparation of the radiolabelled complex showed high radiochemical purity of > 99%. The results show that liver and spleen have received the highest absorbed dose of 1.051 and 0.441 mSv/MBq, respectively. The absorbed dose values for these two dose-limiting tissues suggest more biological studies special in tumor-bearing animals.

Keywords: Radar, internal dosimetry, Lutetium-177

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2 Estimated Human Absorbed Dose of 111In-BPAMD as a New Bone-Seeking SPECT-Imaging Agent

Authors: H. Yousefnia, S. Zolghadri

Abstract:

An early diagnosis of bone metastasis is very important for making a right decision on a subsequent therapy. One of the most important steps to be taken initially, for developing a new radiopharmaceutical is the measurement of organ radiation exposure dose. In this study, the dosimetric studies of a novel agent for SPECT-imaging of the bone metastasis, 111In-(4- {[(bis(phosphonomethyl))carbamoyl]methyl}7,10bis(carboxymethyl) -1,4,7,10-tetraazacyclododec-1-yl) acetic acid (111In-BPAMD) complex, have been carried out to estimate the dose in human organs based on the data derived from mice. The radiolabeled complex was prepared with high radiochemical purity in the optimal conditions. Biodistribution studies of the complex was investigated in the male Syrian mice at the selected times after injection (2, 4, 24 and 48 h). The human absorbed dose estimation of the complex was made based on data derived from the mice by the radiation absorbed dose assessment resource (RADAR) method. 111In-BPAMD complex was prepared with high radiochemical purity >95% (ITLC) and specific activities of 2.85 TBq/mmol. Total body effective absorbed dose for 111In-BPAMD was 0.205 mSv/MBq. This value is comparable to the other 111In clinically used complexes. The results show that the dose with respect to the critical organs is satisfactory within the acceptable range for diagnostic nuclear medicine procedures. Generally, 111In-BPAMD has interesting characteristics and it can be considered as a viable agent for SPECT-imaging of the bone metastasis in the near future.

Keywords: Radar, BPAMD, absorbed dose, In-111

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1 Design, Construction and Performance Evaluation of a HPGe Detector Shield

Authors: M. Sharifi, M. Akbari, M. Mirzaii, F. Bolourinovin, H. Yousefnia, K. Yousefi-Mojir

Abstract:

A multilayer passive shield composed of low-activity lead (Pb), copper (Cu), tin (Sn) and iron (Fe) was designed and manufactured for a coaxial HPGe detector placed at a surface laboratory for reducing background radiation and radiation dose to the personnel. The performance of the shield was evaluated and efficiency curves of the detector were plotted by using of various standard sources in different distances. Monte Carlo simulations and a set of TLD chips were used for dose estimation in two distances of 20 and 40 cm. The results show that the shield reduced background spectrum and the personnel dose more than 95%.

Keywords: HPGe shield, background count, personnel dose, efficiency curve

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Abstracts

29 Absorbed Dose Estimation of 177Lu-DOTATOC in Adenocarcinoma Breast Cancer Bearing Mice

Authors: H. Yousefnia, S. Zolghadri, M. Mousavi-Daramoroudi, F. Abbasi-Davani

Abstract:

In this study, the absorbed dose of human organs after injection of 177Lu-DOTATOC was studied based on the biodistribution of the complex in adenocarcinoma breast cancer bearing mice. For this purpose, the biodistribution of the radiolabelled complex was studied and compartmental modeling was applied to calculate the absorbed dose with high precision. As expected, 177Lu-DOTATOC illustrated a notable specific uptake in tumor and pancreas, organs with high level of somatostatin receptor on their surface and the effectiveness of the radio-conjugate for targeting of the breast adenocarcinoma tumors was indicated. The elicited results of modeling were the exponential equations, and those are utilized for obtaining the cumulated activity data by taking their integral. The results also exemplified that non-target absorbed-doses such as the liver, spleen and pancreas were approximately 0.008, 0.004, and 0.039, respectively. While these values were so much lower than target (tumor) absorbed-dose, it seems due to this low toxicity, this complex is a good agent for therapy.

Keywords: Dosimetry, Breast Cancer, ¹⁷⁷Lu, compartmental modeling

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28 Estimation of Human Absorbed Dose Using Compartmental Model

Authors: H. Yousefnia, S. Zolghadri, M. Mousavi-Daramoroudi, F. Abbasi-Davani

Abstract:

Dosimetry is an indispensable and precious factor in patient treatment planning to minimize the absorbed dose in vital tissues. In this study, compartmental model was used in order to estimate the human absorbed dose of 177Lu-DOTATOC from the biodistribution data in wild type rats. For this purpose, 177Lu-DOTATOC was prepared under optimized conditions and its biodistribution was studied in male Syrian rats up to 168 h. Compartmental model was applied to mathematical description of the drug behaviour in tissue at different times. Dosimetric estimation of the complex was performed using radiation absorbed dose assessment resource (RADAR). The biodistribution data showed high accumulation in the adrenal and pancreas as the major expression sites for somatostatin receptor (SSTR). While kidneys as the major route of excretion receive 0.037 mSv/MBq, pancreas and adrenal also obtain 0.039 and 0.028 mSv/MBq. Due to the usage of this method, the points of accumulated activity data were enhanced, and further information of tissues uptake was collected that it will be followed by high (or improved) precision in dosimetric calculations.

Keywords: Syrian rats, ¹⁷⁷Lu-DOTATOC, compartmental modeling, human absorbed dose

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27 Time Dependent Biodistribution Modeling of 177Lu-DOTATOC Using Compartmental Analysis

Authors: H. Yousefnia, S. Zolghadri, M. Mousavi-Daramoroudi, F. Abbasi-Davani

Abstract:

In this study, 177Lu-DOTATOC was prepared under optimized conditions (radiochemical purity: > 99%, radionuclidic purity: > 99%). The percentage of injected dose per gram (%ID/g) was calculated for organs up to 168 h post injection. Compartmental model was applied to mathematical description of the drug behaviour in tissue at different times. The biodistribution data showed the significant excretion of the radioactivity from the kidneys. The adrenal and pancreas, as major expression sites for somatostatin receptor (SSTR), had significant uptake. A pharmacokinetic model of 177Lu-DOTATOC was presented by compartmental analysis which demonstrates the behavior of the complex.

Keywords: biodistribution, octreotide, ¹⁷⁷Lu, compartmental modeling

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26 A Comparison between Reagents Extracted from Tree Leaves for Spectrophotometric Determination of Hafnium(IV)

Authors: H. Yousefnia, S. Zolghadri, A. Boveiri Monji, B. Salimi

Abstract:

The main goal of this paper was to make use of green reagents as a substitute of perilous synthetic reagents and organic solvents for spectrophotometric determination of hafnium(IV). The extracts taken from six different kinds of tree leaves including Acer negundo, Ficus carica, Cerasus avium, Chimonanthus, Salix babylonica and Pinus brutia, were applied as green reagents for the experiments. In 6-M hydrochloric acid, hafnium reacted with the reagent to form a yellow product and showed maximum absorbance at 421 nm. Among tree leaves, Chimonanthus showed satisfactory results with a molar absorptivity value of 0.61 × 104 l mol-1 cm-1 and the method was linear in the 0.3-9 µg mL -1 concentration range. The detection limit value was 0.064 µg mL-1. The proposed method was simple, low cost, clean, and selective.

Keywords: Synthetic Reagents, hafnium, spectrophotometric determination, tree leaves

Procedia PDF Downloads 35
25 A Green Method for Selective Spectrophotometric Determination of Hafnium(IV) with Aqueous Extract of Ficus carica Tree Leaves

Authors: H. Yousefnia, S. Zolghadri, A. Boveiri Monji, M. Haji Hosseini

Abstract:

A clean spectrophotometric method for the determination of hafnium by using a green reagent, acidic extract of Ficus carica tree leaves is developed. In 6-M hydrochloric acid, hafnium reacts with this reagent to form a yellow product. The formed product shows maximum absorbance at 421 nm with a molar absorptivity value of 0.28 × 104 l mol⁻¹ cm⁻¹, and the method was linear in the 2-11 µg ml⁻¹ concentration range. The detection limit value was found to be 0.312 µg ml⁻¹. Except zirconium and iron, the selectivity was good, and most of the ions did not show any significant spectral interference at concentrations up to several hundred times. The proposed method was green, simple, low cost, and selective.

Keywords: Synthetic Reagents, hafnium, spectrophotometric determination, Ficus caricatree leaves

Procedia PDF Downloads 39
24 Absorbed Dose Estimation of 68Ga-EDTMP in Human Organs

Authors: H. Yousefnia, S. Zolghadri, A. R. Jalilian

Abstract:

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 68Ga-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. 68Ga was obtained from 68Ge/68Ga 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 biodistribution was studied up to 120 min. As expected, major accumulation was observed in the bone. Absorbed dose of each human organ was calculated based on biodistribution in the rats using RADAR method. Bone surface and bone marrow with 0.112 and 0.053 mSv/MBq, respectively, received the highest absorbed dose. According to these results, the radiolabeled complex is a suitable and safe option for PET bone imaging.

Keywords: rats, absorbed dose, EDTMP, ⁶⁸Ga

Procedia PDF Downloads 64
23 Biodistribution Studies of 177Lu-DOTATOC in Mouse Tumor Model: Possible Utilization in Adenocarcinoma Breast Cancer Treatment

Authors: H. Yousefnia, S. Zolghadri, M. Mousavi-Daramoroudi, F. Abbasi-Davani, S. Kakaei

Abstract:

Despite the appropriate characteristics of 177Lu and DOTATOC, to our best knowledge, the therapeutic benefit of 177Lu-DOTATOC complex in breast cancer has not been reported until now. In this study, biodistribution of 177Lu-DOTA-TOC in mouse tumor model for evaluation of possible utilization of this complex in breast cancer treatment was investigated.177Lu was prepared with the specific activity of 2.6-3 GBq.mg-1 and radionuclidic purity higher than 99%. The radiolabeled complex was prepared in the optimized conditions with the radiochemical purity higher than 99%. The final solution was injected to the BALB/c mice with adenocarcinoma breast cancer. The biodistribution results showed major accumulation in the kidneys as the major excretion route and the somatostatin receptor-positive tissues such as pancreas compared with the other tissues. Also, significant uptake was observed in tumor even in longer time after injection. According to the results obtained in this research study, somatostatin receptors expressed in breast cancers can be targeted with DOTATOC analogues especially with 177Lu-DOTATOC as an ideal therapeutic agent.

Keywords: adenocarcinoma breast cancer, BALB/c mice, ¹⁷⁷Lu, DOTATOC

Procedia PDF Downloads 80
22 Compartmental Model Approach for Dosimetric Calculations of ¹⁷⁷Lu-DOTATOC in Adenocarcinoma Breast Cancer Based on Animal Data

Authors: H. Yousefnia, S. Zolghadri, F. Abbasi-Davani, M. S. Mousavi-Daramoroudi

Abstract:

Dosimetry is an indispensable and precious factor in patient treatment planning; to minimize the absorbed dose in vital tissues. In this study, In accordance with the proper characteristics of DOTATOC and ¹⁷⁷Lu, after preparing ¹⁷⁷Lu-DOTATOC at the optimal conditions for the first time in Iran, radionuclidic and radiochemical purity of the solution was investigated using an HPGe spectrometer and ITLC method, respectively. The biodistribution of the compound was assayed for treatment of adenocarcinoma breast cancer in bearing BALB/c mice. The results have demonstrated that ¹⁷⁷Lu-DOTATOC is a profitable selection for therapy of the tumors. Because of the vital role of internal dosimetry before and during therapy, the effort to improve the accuracy and rapidity of dosimetric calculations is necessary. For this reason, a new method was accomplished to calculate the absorbed dose through mixing between compartmental model, animal dosimetry and extrapolated data from animal to human and using MIRD method. Despite utilization of compartmental model based on the experimental data, it seems this approach may increase the accuracy of dosimetric data, confidently.

Keywords: internal dosimetry, biodistribution modeling, compartmental model, ¹⁷⁷Lu-DOTATOC

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21 Biodistribution Study of 68GA-PDTMP as a New Bone Pet Imaging Agent

Authors: H. Yousefnia, S. Zolghadri, A. R. Jalilian, A. Ramazani, N. Tadayon

Abstract:

In this study, 68Ga-PDTMP was prepared as a new agent for bone imaging. 68Ga was obtained from SnO2 based generator. A certain volume of the PDTMP solution was added to the vial containing 68GaCl3 and the pH of the mixture was adjusted to 4 using HEPES. Radiochemical purity of the radiolabelled complex was checked by thin layer chromatography. Biodistribution of this new agent was assessed in rats after intravenously injection of the complex. For this purpose, the rats were killed at specified times after injection and the weight and activity of each organ was measured. Injected dose per gram was calculated by dividing the activity of each organ to the total injected activity and the mass of each organ. As expected the most of the activity was accumulated in the bone tissue. The radiolabelled compound was extracted from blood very fast. This new bone-seeking complex can be considered as a good candidate of PET-based radiopharmaceutical for imaging of bone metastases.

Keywords: Imaging, biodistribution, PDTMP, Ga-68

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20 Preparation and Quality Control of 68Ga-1,2-Propylene Di-Amino Tetra (Methylenephosphonic Acid)

Authors: H. Yousefnia, S. Zolghadri, A. R. Jalilian, A. Ramazani, N. Tadayon

Abstract:

Bone metastases occur in many patients with solid malignant tumors. Recently, 1,2 propylene di-amino tetra methylenephosphonic acid (PDTMP) has been introduced as a suitable carrier in the development of therapeutic bone-avid radiopharmaceuticals. In this study, due to the desirable characteristics of 68Ga, 68Ga-PDTMP was prepared. 68Ga was obtained from SnO2 based generator. A stock solution of PDTMP was prepared by dissolving in 2 N NaOH. A certain volume of the stock solution was added to the vial containing 68GaCl3 and the pH of the mixture was adjusted to 4 using HEPES. Radiochemical purity of the radiolabelled complex was checked by thin layer chromatography. 68Ga-PDTMP was prepared in only 15 min with radiochemical purity of more than 98%. This new bone-seeking complex can be considered as a good candidate of PET-based radiopharmaceutical for imaging of bone metastases.

Keywords: Imaging, PDTMP, bone metastases, Ga-68

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19 Human Absorbed Dose Estimation of a New In-111 Imaging Agent Based on Rat Data

Authors: H. Yousefnia, S. Zolghadri

Abstract:

The measurement of organ radiation exposure dose is one of the most important steps to be taken initially, for developing a new radiopharmaceutical. In this study, the dosimetric studies of a novel agent for SPECT-imaging of the bone metastasis, 111In-1,4,7,10-tetraazacyclododecane-1,4,7,10 tetraethylene phosphonic acid (111In-DOTMP) complex, have been carried out to estimate the dose in human organs based on the data derived from rats. The radiolabeled complex was prepared with high radiochemical purity in the optimal conditions. Biodistribution studies of the complex was investigated in the male Syrian rats at selected times after injection (2, 4, 24 and 48 h). The human absorbed dose estimation of the complex was made based on data derived from the rats by the radiation absorbed dose assessment resource (RADAR) method. 111In-DOTMP complex was prepared with high radiochemical purity of >99% (ITLC). Total body effective absorbed dose for 111In-DOTMP was 0.061 mSv/MBq. This value is comparable to the other 111In clinically used complexes. The results show that the dose with respect to the critical organs is satisfactory within the acceptable range for diagnostic nuclear medicine procedures. Generally, 111In-DOTMP has interesting characteristics and can be considered as a viable agent for SPECT-imaging of the bone metastasis in the near future.

Keywords: Radar, DOTMP, internal dosimetry, In-111

Procedia PDF Downloads 284
18 Estimated Human Absorbed Dose of 111 In-BPAMD as a New Bone-Seeking Spect-Imaging Agent

Authors: H. Yousefnia, S. Zolghadri

Abstract:

An early diagnosis of bone metastases is very important for providing a profound decision on a subsequent therapy. A prerequisite for the clinical application of new diagnostic radiopharmaceutical is the measurement of organ radiation exposure dose from biodistribution data in animals. In this study, the dosimetric studies of a novel agent for SPECT-imaging of bone methastases, 111In-(4-{[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl) acetic acid (111In-BPAMD) complex, have been estimated in human organs based on mice data. The radiolabeled complex was prepared with high radiochemical purity at the optimal conditions. Biodistribution studies of the complex were investigated in male Syrian mice at selected times after injection (2, 4, 24 and 48 h). The human absorbed dose estimation of the complex was performed based on mice data by the radiation absorbed dose assessment resource (RADAR) method. 111In-BPAMD complex was prepared with high radiochemical purity >95% (ITLC) and specific activities of 2.85 TBq/mmol. Total body effective absorbed dose for 111In-BPAMD was 0.205 mSv/MBq. This value is comparable to the other 111In clinically used complexes. The results show that the dose to critical organs the complex is well within the acceptable considered range for diagnostic nuclear medicine procedures. Generally, 111In-BPAMD has interesting characteristics and can be considered as a viable agent for SPECT-imaging of the bone metastases in the near future.

Keywords: Radar, BPAMD, absorbed dose, In-111

Procedia PDF Downloads 286
17 Preparation and Biological Evaluation of 186/188Re-Chitosan for Radiosynovectomy

Authors: H. Yousefnia, A. Bahrami-Samani, N. Ahmadi

Abstract:

Chitosan is a natural and biodegradable polysaccharide with special characteristic for application in intracavital therapy. 166Ho-chitosan has been reported for the treatment of hepatocellular carcinoma and RSV with promising results. The aim of this study was to prepare 186/188Re-chitosan for radiosynovectomy purposes and investigate the probability of its leakage from the knee joint. 186/188Re was produced by neutron irradiation of the natural rhenium in a research reactor. Chemical processing was performed to obtain (186/188Re)-NaReO4- according to the IAEA manual. A stock solution of chitosan was prepared by dissolving in 1 % acetic acid aqueous solution (10 mg/mL). 1.5 mL of this stock solution was added to the vial containing the activity and the mixture was stirred for 5 min in the room temperature. The radiochemical purity of the complex was checked by the ITLC method, showing the purity of higher than 98%. Distribution of the radiolabeled complex was determined after intra-articular injection into the knees of rats. Excellent retention was observed in the joint with approximately no activity in the other organs.

Keywords: chitosan, leakage, radiosynovectomy, rhenium

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16 Evaluation of the Radiolabelled 68GA-DOTATOC Complex in Adenocarcinoma Breast Cancer

Authors: H. Yousefnia, S. Zolghadri, A. R. Jalilian, M. Naderi, A. Ramazani, B. Alirzapour

Abstract:

Nowadays, 68Ga-DOTATOC has been known as a potential agent for the detection of neuroendocrine tumours and it has indicated higher sensitivity compared with the 111In-Octeroetide. The aim of this study was to evaluate the effectiveness of this new agent in the diagnosis of adenocarcinoma breast cancer. 68Ga-DOTATOC was prepared with the radiochemical purity of higher than 98% and by the specific activity of 39.6 TBq/mmol. 37 MBq of the complex was injected intravenously into the BULB/c mice with adenocarcinoma breast cancer. PET/CT images were acquired after 30, 60 and 90 min post injection demonstrated significant accumulation in the tumour sites. Also, considerable activity was observed in the kidney and bladder as the main routs of excretion. Generally, the results showed that 68Ga-DOTATOC can be considered as a suitable complex for diagnosis of the adenocarcinoma breast cancer using PET procedure.

Keywords: Imaging, octreotide, adenocarcinoma breast cancer

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15 Preparation and Quality Control of a New Radiolabelled Complex of Spion

Authors: H. Yousefnia, S. Zolghadri, A. Bahrami-Samani, SJ. Ahmadi, S. Sajadi, M. Bagherzadeh

Abstract:

Nowadays, superparamagnetic iron oxide nanoparticles (SPIONs) as the multitask agents have showed advantageous characteristics. The aim of this study was the preparation and quality control of 153Sm-DTPA-DA-SPION complex. Samarium-153 was produced by neutron irradiation of the enriched 152Sm2O3 in a research reactor for 5 d. For radiolabeling purposes, 8 mg of the ligand was added to the vial containing 153SmCl3 and the mixture was sonicated 30 min, while pH was adjusted to 7-8. The radiochemical purity of the complex was checked by the ITLC method using NH4OH:MeOH:H2O (0.2:2:4) as the mobile phase. This new radiolabeled complex was prepared with a radiochemical purity of higher than 98% in 30 min at the optimized condition. The complex was kept at room temperature and in human serum at 37 °C for 48 h, showed no loss of 153Sm from the complex. Considering all of these features, this new radiolabeled complex can be considered as a good therapeutic agent; however, further studies on its biological behavior are still needed.

Keywords: Quality Control, Preparation, iron nanoparticles

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14 Preliminary dosimetric Evaluation of a New Therapeutic 177LU Complex for Human Based on Biodistribution Data in Rats

Authors: H. Yousefnia, S. Zolghadri, A. Golabi Dezfuli

Abstract:

Tris (1,10-phenanthroline) lanthanum(III)] trithiocyanate is a new compound that has shown to stop DNA synthesis in CCRF-CEM and Ehrlich ascites cells leading to a cell cycle arrest in G0/G1. One other important property of the phenanthroline nucleus is its ability to act as a triplet-state photosensitizer especially in complexes with lanthanides. In Nowadays, the radiation dose assessment resource (RADAR) method is known as the most common method for absorbed dose calculation. 177Lu was produced by irradiation of a natural Lu2O3 target at a thermal neutron flux of approximately 4 × 1013 n/cm2•s. 177Lu-PL3 was prepared in the optimized condition. The radiochemical yield was checked by ITLC method. The biodistribution of the complex was investigated by intravenously injection to wild-type rats via their tail veins. In this study, the absorbed dose of 177Lu-PL3 to human organs was estimated by RADAR method. 177Lu was prepared with a specific activity of 2.6-3 GBq.mg-1 and radionuclide purity of 99.98 %. The 177Lu-PL3 complex can prepare with high radiochemical yield (> 99 %) at optimized conditions. The results show that liver and spleen have received the highest absorbed dose of 1.051 and 0.441 mSv/MBq, respectivley. The absorbed dose values for these two dose-limiting tissues suggest more biological studies special in tumor-bearing animals.

Keywords: Animals, Radar, internal dosimetry, Lutetium-177

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13 Design, Construction and Performance Evaluation of a HPGe Detector Shield

Authors: M. Sharifi, M. Akbari, M. Mirzaii, F. Bolourinovin, H. Yousefnia, K. Yousefi-Mojir

Abstract:

A multilayer passive shield composed of low-activity lead (Pb), copper (Cu), tin (Sn) and iron (Fe) was designed and manufactured for a coaxial HPGe detector placed at a surface laboratory for reducing background radiation and radiation dose to the personnel. The performance of the shield was evaluated and efficiency curves of the detector were plotted by using of the various standard sources in different distances. Monte Carlo simulations and a set of TLD chips were used for dose estimation in two distances of 20 and 40 cm. The results show that the shield reduced background spectrum and the personnel dose more than 95%.

Keywords: HPGe shield, background count, personnel dose, efficiency curve

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12 Optimization and Evaluation of 177lu-Dotatoc as a Potential Agent for Peptide Receptor Radionuclide Therapy

Authors: H. Yousefnia, S. Zolghadri, F. Abbasi-Davani, MS. Mousavi-Daramoroudi

Abstract:

High expression of somatostatin receptors on a wide range of human tumours makes them as potential targets for peptide receptor radionuclide tomography. A series of octreotide analogues were synthesized while [DOTA-DPhe1, Tyr3]octreotide (DOTATOC) indicated advantageous properties in tumour models. In this study, 177Lu-DOTATOC was prepared with the radiochemical purity of higher than 99% in 30 min at the optimized condition. Biological behavior of the complex was studied after intravenous injection into the Syrian rats. Major difference uptake was observed compared to 177LuCl3 solution especially in somatostatin receptor-positive tissues such as pancreas and adrenal.

Keywords: biodistribution, octreotide, Syrian rats

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11 Preparation and Quality Control of a Novel Radiolabeled Complex of 166ho for the Treatment of Somatostatin Receptor Expressing Tumours

Authors: H. Yousefnia, S. Zolghadri, A. Golabi Dezfuli, M. Hosntalab

Abstract:

Peptide receptor radionuclide therapy is nowadays used for the treatment of various abnormalities with somatostatin receptors. In this study, 166Ho-DOTATOC was prepared and the best conditions for its radiolabeling was obtained. For this purpose, a certain of DOTATOC was added to a vial containing 166Ho. various experiments by varying ligand concentration, pH, temperature and time were performed to determine the best conditions. Radiochemical purity of the complex was assessed by instant thin layer chromatography method utilizing 0.9% NaCl as the mobile phase. 166Ho-DOTATOC was prepared with radiochemical purity of higher than 95% at the optimized condition (pH=4, temperature: 95° C, time:30 min). In 0.9% NaCl, free Ho cation was developed at Rf of 0.8 while the complex was remained at the front of the paper.

Keywords: Quality Control, Neuroendocrine, octreotide, Ho-166

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10 Human Absorbed Dose Assessment of 68Ga-Dotatoc Based on Biodistribution Data in Syrian Rats

Authors: H. Yousefnia, S. Zolghadri, A. R. Jalilian, M. Naderi, A. Ramazani

Abstract:

The aim of this work was to evaluate the values of absorbed dose of 68Ga-DOTATOC in numerous human organs. 68Ga-DOTATOC was prepared with the radiochemical purity of higher than 98% and by specific activity of 39.6 MBq/nmol. The complex demonstrated great stability at room temperature and in human serum at 37° C at least 2 h after preparation. Significant uptake was observed in somatostatin receptor-positive tissues such as pancreas and adrenal. The absorbed dose received by human organs was evaluated based on biodistribution studies in Syrian rats by the radiation absorbed dose assessment resource (RADAR) method. Maximum absorbed dose was obtained in the pancreas, kidneys, and adrenal with 0.105, 0.074, and 0.010 mGy/MBq, respectively. The effective absorbed dose was 0.026 mSv/MBq for 68Ga-DOTATOC. The results showed that 68Ga-DOTATOC can be considered as a safe and effective agent for clinically PET imaging applications.

Keywords: MIRD, effective absorbed dose, Ga-68, octreotide

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9 Comparative Study between the Absorbed Dose of 67ga-Ecc and 68ga-Ecc

Authors: H. Yousefnia, S. Zolghadri, A. R. Jalilian, S. Shanesazzadeh, A.Lahooti

Abstract:

In this study, 68Ga-ECC and 67Ga-ECC were both prepared with the radiochemical purity of higher than 97% in less than 30 min. The biodistribution data for 68Ga-ECC showed the extraction of the most of the activity from the urinary tract. The absorbed dose was estimated based on biodistribution data in mice by the medical internal radiation dose (MIRD) method. Comparison between human absorbed dose estimation for these two agents indicated the values of approximately ten-fold higher after injection of 67Ga-ECC than 68Ga-ECC in the most organs. The results showed that 68Ga-ECC can be considered as a more potential agent for renal imaging compared to 67Ga-ECC.

Keywords: effective absorbed dose, ethylenecysteamine cysteine, Ga-67, Ga-68

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8 Development of 90y-Chitosan Complex for Radiosynovectomy

Authors: H. Yousefnia, S. Zolghadri, A. R. Jalilian, A. Mirzaei, M. Athari-Allaf

Abstract:

Rheumatoid arthritis is the most common autoimmune disease, leading to the destruction of the joints. The aim of this study was the preparation of 90Y-chitosan complex as a novel agent for radiosynovectomy. The complex was prepared in the diluted acetic acid solution. At the optimized condition, the radiochemical purity of higher than 99% was obtained by ITLC method on Whatman No. 1 and by using a mixture of methanol/water/acetic acid (4:4:2) as the mobile phase. The complex was stable in acidic media (pH=3) and its radiochemical purity was above 98% even after 48 hours. The biodistribution data in rats showed that there was no significant leakage of the injected activity even after 48 h. Considering all of the excellent features of the complex, 90Y-chitosan can be used to manipulate synovial inflammation effectively.

Keywords: chitosan, biodistribution, Y-90, radiosynovectomy

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7 Production and Quality Control of a Novel 153Sm-Complex for Radiotherapy of Bone-Metastases

Authors: H. Yousefnia, S. Zolghadri, A. Bahrami-Samani, R. Enayati, M. Hosntalab

Abstract:

Bone metastases occur in many cases at an early stage of the tumour disease, however their symptoms are recognized rather late. The aim of this study was the preparation of 153Sm-(4-{[bis-(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl) 1,4,7,10-tetraazacyclododec-1-yl) acetic acid (BPAMD) for bone pain palliation therapy. 153Sm was produced at Tehran research reactor via 152Sm(n,γ)153Sm reaction. 200 µl of 1mg/ml BPAMD solution was added to the vial containing 1 mCi 153Sm and the mixture was heated up to 90 0C for 1 h. The radiochemical purity of the complex was measured by ITLC method. The final solution with radiochemical purity of more than 95% was injected to BALB mice and bio distribution was determined up to 48 h. SPECT images were acquired after 2 and 24 h post injection. While high bone uptake was confirmed by both the bio distribution studies and SPECT imaging, accumulation in other organs was approximately negligible. The results show that 153Sm-BPAMD can be used as an excellent tracer for bone pain palliation therapy.

Keywords: radiotherapy, BPAMD, bone metastases

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6 Production, Quality Control and Biodistribution Assessment of 166 Ho-BPAMD as a New Bone Seeking Agent

Authors: H. Yousefnia, S. Zolghadri, A. Bahrami-Samani, N. Amraee, M. Hosntalab

Abstract:

The aim of this study was the preparation of a new agent for bone marrow ablation in patients with multiple myeloma. 166Ho was produced at Tehran research reactor via 165Ho(n,γ)166Ho reaction. Complexion of Ho‐166 with BPAMD was carried out by the addition of about 200µg of BPAMD in absolute water to 1 mci of 166HoCl3 and warming up the mixture 90 0C for 1 h. 166Ho-BPAMD was prepared successfully with radio chemical purity of 95% which was measured by ITLC method. The final solution was injected to wild-type mice and bio distribution was determined up to 48 h. SPECT images were acquired after 2 and 48 h post injection. Both the bio distribution studies and SPECT imaging indicated high bone uptake, while accumulation in other organs was approximately negligible. The results show that 166Ho-BPAMD has suitable characteristics and can be used as a new bone marrow ablative agent.

Keywords: SPECT, BPAMD, bone marrow ablation

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5 Production, Quality Control, and Biodistribution Assessment of 111In-BPAMD as a New Bone Imaging Agent

Authors: H. Yousefnia, S. Zolghadri, A. R. Jalilian, A. Mirzaei, A. Aghanejad, R. Enayati

Abstract:

Bone metastases occur in many cases at an early stage of the tumour disease; however, their symptoms are recognized rather late. The aim of this study was the preparation and quality control of 111In-BPAMD for diagnostic purposes. 111In was produced at the Agricultural, Medical, and Industrial Research School (AMIRS) by means of 30 MeV cyclotron via natCd(p,x)111In reaction. Complexion of In‐111 with BPAMD was carried out by using acidic solution of 111InCl3 and BPAMD in absolute water. The effect of various parameters such as temperature, ligand concentration, pH, and time on the radiolabeled yield was studied. 111In-BPAMD was prepared successfully with the radiochemical purity of 95% at the optimized condition (100 µg of BPAMD, pH=5, and at 90°C for 1 h) which was measured by ITLC method. The final solution was injected to wild-type mice and biodistribution was determined up to 72 h. SPECT images were acquired after 2 and 24 h post injection. Both the biodistribution studies and SPECT imaging indicated high bone uptake while accumulation in other organs was approximately negligible. The results show that 111In-BPAMD can be used as an excellent tracer for diagnosis of bone metastases by SPECT imaging.

Keywords: biodistribution, SPECT, BPAMD

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4 Preliminary Dosimetric Evaluation of Two New 153Sm Bone Pain Palliative Agents

Authors: H. Yousefnia, S. Zolghadri, AR. Jalilian, N. Amraee, Z. Naseri

Abstract:

The purpose of this study was to calculate the absorbed dose to each human organ for two new Sm-153 bone-seeking agents in order to evaluate their effectiveness in bone pain palliation therapy. In this work, the absorbed dose of 153Sm-TTHMP and 153Sm-PDTMP to each human organ was evaluated based on biodistribution studies in rats by radiation dose assessment resource (RADAR) method. The highest absorbed dose for 153Sm-TTHMP and 153Sm-PDTMP is observed in trabecular bone with 1.844 and 3.167 mGy/MBq, respectively. Bone/red marrow dose ratio, as the target/critical organ dose ratio, for 153Sm-PDTMP is greater than 153Sm-TTHMP and is compatible with 153Sm-EDTMP. The results showed that these bone-seeking agents, specially 153Sm-PDTMP, have considerable characteristics compared to the most clinically used bone pain palliative radiopharmaceutical, and therefore, can be good candidates for bone pain palliation in patients with bone metastasis; however, further biological studies in other mammals are still needed.

Keywords: internal dosimetry, PDTMP, TTHMP

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3 Development of 111In-DOTMP as a New Bone Imaging Agent

Authors: H. Yousefnia, S. Zolghadri, AR. Jalilian, A. Mirzaei, A. Bahrami-Samani, M. Erfani

Abstract:

The objective of this study is the preparation of 111In-DOTMP as a new bone imaging agent. 111In was produced at the Agricultural, Medical and Industrial Research School (AMIRS) by means of 30 MeV cyclotron via natCd(p,x)111In reaction. Complexion of In‐111 with DOTMP was carried out by adding 0.1 ml of the stock solution (50 mg/ml in 2 N NaoH) to the vial containing 1 mCi of 111In. pH of the mixture was adjusted to 7-8 by means of phosphate buffer. The radiochemical purity of the complex at the optimized condition was higher than 98% (by using whatman No.1 paper in NH4OH:MeOH: H2O (0.2:2:4)). Both the biodistribution studies and SPECT imaging indicated high bone uptake. The ratio of bone to other soft tissue accumulation was significantly high which permit to observe high quality images. The results show that 111In-DOTMP can be used as a suitable tracer for diagnosis of bone metastases by SPECT imaging.

Keywords: biodistribution, DOTMP, SPECT

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2 Comparison of Water Equivalent Ratio of Several Dosimetric Materials in Proton Therapy Using Monte Carlo Simulations and Experimental Data

Authors: H. Yousefnia, M. R. Akbari, E. Mirrezaei

Abstract:

Range uncertainties of protons are currently a topic of interest in proton therapy. Two of the parameters that are often used to specify proton range are water equivalent thickness (WET) and water equivalent ratio (WER). Since WER values for a specific material is nearly constant at different proton energies, it is a more useful parameter to compare. In this study, WER values were calculated for different proton energies in polymethyl methacrylate (PMMA), polystyrene (PS) and aluminum (Al) using FLUKA and TRIM codes. The results were compared with analytical, experimental and simulated SEICS code data obtained from the literature. In FLUKA simulation, a cylindrical phantom, 1000 mm in height and 300 mm in diameter, filled with the studied materials was simulated. A typical mono-energetic proton pencil beam in a wide range of incident energies usually applied in proton therapy (50 MeV to 225 MeV) impinges normally on the phantom. In order to obtain the WER values for the considered materials, cylindrical detectors, 1 mm in height and 20 mm in diameter, were also simulated along the beam trajectory in the phantom. In TRIM calculations, type of projectile, energy and angle of incidence, type of target material and thickness should be defined. The mode of 'detailed calculation with full damage cascades' was selected for proton transport in the target material. The biggest difference in WER values between the codes was 3.19%, 1.9% and 0.67% for Al, PMMA and PS, respectively. In Al and PMMA, the biggest difference between each code and experimental data was 1.08%, 1.26%, 2.55%, 0.94%, 0.77% and 0.95% for SEICS, FLUKA and SRIM, respectively. FLUKA and SEICS had the greatest agreement (≤0.77% difference in PMMA and ≤1.08% difference in Al, respectively) with the available experimental data in this study. It is concluded that, FLUKA and TRIM codes have capability for Bragg curves simulation and WER values calculation in the studied materials. They can also predict Bragg peak location and range of proton beams with acceptable accuracy.

Keywords: Monte Carlo simulations, water equivalent ratio, dosimetric materials, proton therapy

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1 Comparison of FNTD and OSLD Detectors' Responses to Light Ion Beams Using Monte Carlo Simulations and Exprimental Data

Authors: A. Ghasemi, H. Yousefnia, M. R. Akbari

Abstract:

Al2O3:C,Mg fluorescent nuclear track detector (FNTD) and Al2O3:C optically stimulated luminescence detector (OSLD) are becoming two of the applied detectors in ion dosimetry. Therefore, the response of these detectors to hadron beams is highly of interest in radiation therapy (RT) using ion beams. In this study, these detectors' responses to proton and Helium-4 ion beams were compared using Monte Carlo simulations. The calculated data for proton beams were compared with Markus ionization chamber (IC) measurement (in water phantom) from M.D. Anderson proton therapy center. Monte Carlo simulations were performed via the FLUKA code (version 2011.2-17). The detectors were modeled in cylindrical shape at various depths of the water phantom without shading each other for obtaining relative depth dose in the phantom. Mono-energetic parallel ion beams in different incident energies (100 MeV/n to 250 MeV/n) were collided perpendicularly on the phantom surface. For proton beams, the results showed that the simulated detectors have over response relative to IC measurements in water phantom. In all cases, there were good agreements between simulated ion ranges in the water with calculated and experimental results reported by the literature. For proton, maximum peak to entrance dose ratio in the simulated water phantom was 4.3 compared with about 3 obtained from IC measurements. For He-4 ion beams, maximum peak to entrance ratio calculated by both detectors was less than 3.6 in all energies. Generally, it can be said that FLUKA is a good tool to calculate Al2O3:C,Mg FNTD and Al2O3:C OSLD detectors responses to therapeutic proton and He-4 ion beams. It can also calculate proton and He-4 ion ranges with a reasonable accuracy.

Keywords: comparison, FNTD and OSLD detectors response, light ion beams, Monte Carlo simulations

Procedia PDF Downloads 192