Objective： Estimation of activity accumulated in tumor and organs is very important in predicting the response of radiopharmaceuticals treatment. In this study, we synthesized ~77Lutetium （177Lu）-trastuzumabiron ox...Objective： Estimation of activity accumulated in tumor and organs is very important in predicting the response of radiopharmaceuticals treatment. In this study, we synthesized ~77Lutetium （177Lu）-trastuzumabiron oxide nanoparticles as a double radiopharmaceutical agent for treatment and better estimation of organ activity in a new way by magnetic resonance imaging （MRI）. Methods： ^177Lu-trastuzumab-iron oxide nanoparticles were synthesized and all the quality control tests such as labeling yield, nanoparticle size determination, stability in buffer and blood serum up to 4 d, immunoreactivity and biodistribution in normal mice were determined. In mice bearing breast tumor, liver and tumor activities were calculated with three methods： single photon emission computed tomography （SPECT）, MRI and organ extraction, which were compared with each other. Results： The good results of quality control tests （labeling yield： 61%±2%, mean nanoparticle hydrodynamic size： 41±15 nm, stability in buffer： 86%±5%, stability in blood serum： 80%±3%, immunoreactivity： 80%±2%） indicated that ^177Lu-trastuzumab-iron oxide nanoparticles could be used as a double radiopharmaceutical agent in mice bearing tumor. Results showed that ^177Lu-trastuzumab-iron oxide nanoparticles with MRI had the ability to measure organ activities more accurate than SPECT. Conclusions： Co-conjugating radiopharmaceutical to MRI contrast agents such as iron oxide nanoparticles may be a good way for better dosimetry in nuclear medicine treatment.展开更多
Radiopharmaceuticals are used in nuclear medicine for diagnostic or therapeutic acts. The short decay half-lives of medical radioisotopes, especially those used for diagnostics, imply that they should be produced cont...Radiopharmaceuticals are used in nuclear medicine for diagnostic or therapeutic acts. The short decay half-lives of medical radioisotopes, especially those used for diagnostics, imply that they should be produced continuously and transported as quickly as possible to the medical units where they are used. Neutron-rich medical radioisotopes are generally produced in research reactors, like technetium-99m, lutetium-177, holmium-166 and iodine-131. On the other hand, proton-rich radioisotopes are produced via reactions with charged particles from accelerators like fluorine-18, gallium-67, iodine-123 and thallium-201. Beside this, innovative nuclear reactors are advocated as solutions to the issues of nuclear waste production and proliferation threats. Fast neutron, thorium-cycle and accelerator-driven subcritical (ADS) reactors are some of the most promising of them, proposed as safer fuel breeders and “waste burners”. This article examines the use of a fast thorium-cycle ADS with liquid lead-bismuth eutectic coolant for the production of molybdenum-99/technetium-99m and lutetium-177. Burnup simulation has been made with the Monte-Carlo (MC) code SERPENT. It is demonstrated that MC codes can advantageously be used to determine the optimal irradiation time for a given radioisotope in a realistic reactor core. It is also shown that fast thorium-cycle ADS is an economical option for the production of medical radioisotopes.展开更多
This study was done to quality assure the Hawkeye SPECT/CT at the St. Olav’s hospital and create a clinical method for doing individual dosimetry with <sup>177</sup>Lu-octreotate in targeted radionuclide ...This study was done to quality assure the Hawkeye SPECT/CT at the St. Olav’s hospital and create a clinical method for doing individual dosimetry with <sup>177</sup>Lu-octreotate in targeted radionuclide therapy for neuroendocrine tumors. Various quality control parameters were performed on Infinia Hawkeye SPECT/CT. A calibration dose of 160% ± 2% MBq was ordered and first calibrated for all the dose calibrators. The uniformity test was obtained using a 40 MBq Tc-99m point source positioned 2.5 m away from the two detectors. A 200 MBq Tc-99m was diluted in 70 ml of water, dispersed in six syringes for the registration test. A Lu-177 point source was placed in front of the detectors, one at a time, to check the energy peaks. The Jaczczak phantom with a hollow sphere set (volumes: 0.5, 1, 2, 4, 8, and 16) ml with an additional 60 ml sphere was used for the 3D sensitivity and recovery with Lu-177. Total activity of 945.3 MBq was added to 160 ml of water yielding an activity concentration of 5.908 MBq/ml in the spheres. The phantom was then scanned at various time intervals. A cylindrical phantom with a volume of 6283 ml was also used to obtain the cross-calibration measurement (cps/MBq). Total activity of 995.6 MBq was added and the phantom was scanned at days 0, 6, 13 and 23. The dose calibration factor was changed from 762 to 760 to achieve correct doses. The 2D mean sensitivity factor was 5.56 cps/MBq. Uniformities for both detectors were approved after iteration calibration of the PM tubes. The X-ray to SPECT registration was found to be accurate and within specifications. The energy peak test revealed off-centered 208 keV energy peaks for the two detectors. Quality assurance of imaging devices using radiation is essential for radiation protection and ensures a high-quality image.展开更多
A lutetium 177 (<sup>177</sup>Lu) radiopharmaceutical has been used as a theragnostic agent in molecular radiotherapies. This study aimed to produce images simulating those obtained in a total body imaging...A lutetium 177 (<sup>177</sup>Lu) radiopharmaceutical has been used as a theragnostic agent in molecular radiotherapies. This study aimed to produce images simulating those obtained in a total body imaging study with hot lesions to assess and investigate the image quality of the Hawkeye SPECT/CT images from Lu-177. The NEMA image quality phantom (PTW) with spheres (inner diameters of 10, 13, 17, 22, 28 and 37 mm) and lung insert was used. The measured volume in the background of the current phantom setting was 9482 mL. The five smaller spheres were filled with an activity concentration of 0.461 MBq/mL and the biggest sphere was filled with water. The phantom was placed on the couch and scanned at four hot sphere-to-background concentrations, which are no background, 16:1, 8:1 and 4:1. The images obtained from the scans were imported onto the OXIRIS image analysis tool. Regions of interest (ROIs) were drawn on each sphere of the reconstructed SPECT image. Image contrast and background variability ratios for hot spheres were used as measures of image quality. In addition, the accuracy of corrections were determined from the uniform background and cold lung insert regions. The 37 mm cold sphere had the highest percent contrast, whiles the 10 mm hot sphere had the least for the various hot sphere to background ratios. The background variability for each hot sphere was also determined. The average lung residual error was calculated to be 23.13% for the 16:1 and 22.57% for both the 8:1 and 4:1 hot sphere to background ratio. The results show that the scanner has very good overall performance.展开更多
Carbohydrate antigen 19–9(CA19–9)with multi epitopes relatively high expresses on colorectal cancer(CRC)cells,making it an attractive target for developing radioimmunotherapy(RIT)for CRC.The lutetium-177(^(177)Lu)la...Carbohydrate antigen 19–9(CA19–9)with multi epitopes relatively high expresses on colorectal cancer(CRC)cells,making it an attractive target for developing radioimmunotherapy(RIT)for CRC.The lutetium-177(^(177)Lu)labeled monoclonal antibodies(mA bs)can selectively bind the corresponding antigens and release targeted cytotoxic radiation,which could induce cell apoptosis and reduce the drug-induced resistance.Here,a series of CA19–9 m Abs were labeled with zirconium-89(^(89)Zr),and one with high tumor uptake was screened via PET imaging,which has potential application for the diagnosis of CRC.Then the screened m Ab(C003)labeled with^(177)Lu was utilized for CA19–9 targeted RIT,which presents a significant suppression effect on the growth of colo205 xenografts than immunotherapy alone.Meanwhile,the side effects of ^(177)Lu-DOTA-C003 are limited according to the results of in vivo study.Both89Zr-DFO-C003for CRC immune-PET imaging and ^(177)Lu-DOTA-C003 for RIT against CRC exhibit good potential in clinical applications.展开更多
文摘Objective： Estimation of activity accumulated in tumor and organs is very important in predicting the response of radiopharmaceuticals treatment. In this study, we synthesized ~77Lutetium （177Lu）-trastuzumabiron oxide nanoparticles as a double radiopharmaceutical agent for treatment and better estimation of organ activity in a new way by magnetic resonance imaging （MRI）. Methods： ^177Lu-trastuzumab-iron oxide nanoparticles were synthesized and all the quality control tests such as labeling yield, nanoparticle size determination, stability in buffer and blood serum up to 4 d, immunoreactivity and biodistribution in normal mice were determined. In mice bearing breast tumor, liver and tumor activities were calculated with three methods： single photon emission computed tomography （SPECT）, MRI and organ extraction, which were compared with each other. Results： The good results of quality control tests （labeling yield： 61%±2%, mean nanoparticle hydrodynamic size： 41±15 nm, stability in buffer： 86%±5%, stability in blood serum： 80%±3%, immunoreactivity： 80%±2%） indicated that ^177Lu-trastuzumab-iron oxide nanoparticles could be used as a double radiopharmaceutical agent in mice bearing tumor. Results showed that ^177Lu-trastuzumab-iron oxide nanoparticles with MRI had the ability to measure organ activities more accurate than SPECT. Conclusions： Co-conjugating radiopharmaceutical to MRI contrast agents such as iron oxide nanoparticles may be a good way for better dosimetry in nuclear medicine treatment.
文摘Radiopharmaceuticals are used in nuclear medicine for diagnostic or therapeutic acts. The short decay half-lives of medical radioisotopes, especially those used for diagnostics, imply that they should be produced continuously and transported as quickly as possible to the medical units where they are used. Neutron-rich medical radioisotopes are generally produced in research reactors, like technetium-99m, lutetium-177, holmium-166 and iodine-131. On the other hand, proton-rich radioisotopes are produced via reactions with charged particles from accelerators like fluorine-18, gallium-67, iodine-123 and thallium-201. Beside this, innovative nuclear reactors are advocated as solutions to the issues of nuclear waste production and proliferation threats. Fast neutron, thorium-cycle and accelerator-driven subcritical (ADS) reactors are some of the most promising of them, proposed as safer fuel breeders and “waste burners”. This article examines the use of a fast thorium-cycle ADS with liquid lead-bismuth eutectic coolant for the production of molybdenum-99/technetium-99m and lutetium-177. Burnup simulation has been made with the Monte-Carlo (MC) code SERPENT. It is demonstrated that MC codes can advantageously be used to determine the optimal irradiation time for a given radioisotope in a realistic reactor core. It is also shown that fast thorium-cycle ADS is an economical option for the production of medical radioisotopes.
文摘This study was done to quality assure the Hawkeye SPECT/CT at the St. Olav’s hospital and create a clinical method for doing individual dosimetry with <sup>177</sup>Lu-octreotate in targeted radionuclide therapy for neuroendocrine tumors. Various quality control parameters were performed on Infinia Hawkeye SPECT/CT. A calibration dose of 160% ± 2% MBq was ordered and first calibrated for all the dose calibrators. The uniformity test was obtained using a 40 MBq Tc-99m point source positioned 2.5 m away from the two detectors. A 200 MBq Tc-99m was diluted in 70 ml of water, dispersed in six syringes for the registration test. A Lu-177 point source was placed in front of the detectors, one at a time, to check the energy peaks. The Jaczczak phantom with a hollow sphere set (volumes: 0.5, 1, 2, 4, 8, and 16) ml with an additional 60 ml sphere was used for the 3D sensitivity and recovery with Lu-177. Total activity of 945.3 MBq was added to 160 ml of water yielding an activity concentration of 5.908 MBq/ml in the spheres. The phantom was then scanned at various time intervals. A cylindrical phantom with a volume of 6283 ml was also used to obtain the cross-calibration measurement (cps/MBq). Total activity of 995.6 MBq was added and the phantom was scanned at days 0, 6, 13 and 23. The dose calibration factor was changed from 762 to 760 to achieve correct doses. The 2D mean sensitivity factor was 5.56 cps/MBq. Uniformities for both detectors were approved after iteration calibration of the PM tubes. The X-ray to SPECT registration was found to be accurate and within specifications. The energy peak test revealed off-centered 208 keV energy peaks for the two detectors. Quality assurance of imaging devices using radiation is essential for radiation protection and ensures a high-quality image.
文摘A lutetium 177 (<sup>177</sup>Lu) radiopharmaceutical has been used as a theragnostic agent in molecular radiotherapies. This study aimed to produce images simulating those obtained in a total body imaging study with hot lesions to assess and investigate the image quality of the Hawkeye SPECT/CT images from Lu-177. The NEMA image quality phantom (PTW) with spheres (inner diameters of 10, 13, 17, 22, 28 and 37 mm) and lung insert was used. The measured volume in the background of the current phantom setting was 9482 mL. The five smaller spheres were filled with an activity concentration of 0.461 MBq/mL and the biggest sphere was filled with water. The phantom was placed on the couch and scanned at four hot sphere-to-background concentrations, which are no background, 16:1, 8:1 and 4:1. The images obtained from the scans were imported onto the OXIRIS image analysis tool. Regions of interest (ROIs) were drawn on each sphere of the reconstructed SPECT image. Image contrast and background variability ratios for hot spheres were used as measures of image quality. In addition, the accuracy of corrections were determined from the uniform background and cold lung insert regions. The 37 mm cold sphere had the highest percent contrast, whiles the 10 mm hot sphere had the least for the various hot sphere to background ratios. The background variability for each hot sphere was also determined. The average lung residual error was calculated to be 23.13% for the 16:1 and 22.57% for both the 8:1 and 4:1 hot sphere to background ratio. The results show that the scanner has very good overall performance.
基金supported by the National Natural Science Foundation of China(Nos.21976167,U20A20384)the CAEP Innovation and Development Foundation(No.CX20200003)+2 种基金Nuclear Energy Development Project of State Administration of Science,Technology and Industry for National Defense(No.20201192–1)Key R&D Project of Sichuan Science and Technology Program(No.2020YFS0030)the Central Guidance for Local Science and Technology Development Projects(No.202138–03)。
文摘Carbohydrate antigen 19–9(CA19–9)with multi epitopes relatively high expresses on colorectal cancer(CRC)cells,making it an attractive target for developing radioimmunotherapy(RIT)for CRC.The lutetium-177(^(177)Lu)labeled monoclonal antibodies(mA bs)can selectively bind the corresponding antigens and release targeted cytotoxic radiation,which could induce cell apoptosis and reduce the drug-induced resistance.Here,a series of CA19–9 m Abs were labeled with zirconium-89(^(89)Zr),and one with high tumor uptake was screened via PET imaging,which has potential application for the diagnosis of CRC.Then the screened m Ab(C003)labeled with^(177)Lu was utilized for CA19–9 targeted RIT,which presents a significant suppression effect on the growth of colo205 xenografts than immunotherapy alone.Meanwhile,the side effects of ^(177)Lu-DOTA-C003 are limited according to the results of in vivo study.Both89Zr-DFO-C003for CRC immune-PET imaging and ^(177)Lu-DOTA-C003 for RIT against CRC exhibit good potential in clinical applications.
