Search

NHL is the most common hematologic cancer in adults. Rituximab is the FDA approved treatment of relapsed or refractory low grade B-cell Non-Hodgkin Lymphoma (NHL). But patients eventually become resistant to rituximab. Since lymphocytes and lymphoma cells are highly radiosensitive, low grade NHL that has relapsed or refractory to standard therapy is treated by RIT in which a beta-emitting radionuclide coupled to anti-CD20 antibody. The association of beta emitter radionuclide to rituximab enhances its therapeutic efficacy. The cells which lack antigen or cells which cannot be reached due to poor vascularization and intratumoral pressure in a bulky tumor would be irradiated and killed by cross fire effect of beta emitter. 90Y, a pure high energy β-emitter with a half-life of 64 h, a maximum energy of 2.28 MeV, and maximum board of 11.3 mm in tissue is radionuclide of choice for radioimmunotherapy of outpatient administration. In this study, rituximab was conjugated to DOTA and radiolabeled with 90YCl3. The stability, affinity, and immunoreactivity of radiolabeled antibody was determined in vitro and the conditions were optimized. Biodistribution studies were done in normal mice. The optimum conditions of conjugation and radiolabeling was 1-2 h at 37 °C and 1 h at 45 °C, respectively. Results showed approximately 4 DOTA molecules conjugated per antibody molecule. The purified antibody was stable and intact over 6 months stored at -20 °C. The result of immunoreactivity (≈70%), affinity (≈3 nM) and biodistribution in normal mice are acceptable. [ABSTRACT FROM AUTHOR]

Nanoparticles are generally cleared by the reticuloendothelial system, taken up by Kupffer cells in liver. This principle can be used for liver imaging. Chitosan is an excellent biocompatible and biodegradable polymer. In this study, the authors synthesized99mTc-chitosan nanoparticles and evaluated its potential for liver imaging. Chitosan nanoparticles were synthesized and radiolabeled with99mTc. The labeling efficiency, stability, biodistribution, and imaging study in the normal mice was performed. Biodistribution and imaging studies demonstrated an efficient accumulation of the radiolabeled nanoparticles in the mice liver and indicated the99mTc-chitosan nanoparticles may be considered as a promising radiopharmaceutical for liver imaging. [ABSTRACT FROM AUTHOR]

Aim: In the present study, we investigated the therapeutic efficacy of trastuzumab labeled with lutetium-177 (177Lu) in mice bearing breast tumors. Materials and methods: Trastuzumab was labeled with 177Lu via D OTA as a chelator. In vitro and in vivo quality control tests of incorporated activity, immunoreactivity, stability of 177Lu-trastuzumab, biodistribution, and imaging studies were performed. Therapeutic efficacy and dosimetry studies were carried out in mice with breast tumors. Results: The good in vitro and in vivo quality control results suggested that 177Lu-trastuzumab could be used as a radioimmunotherapy agent. Reductions of 81% and 98% in the mean tumor volume for the group that received 177Lu-trastuzumab [7.4 MBq] were observed at 42 and 45 days after treatment, respectively. Conclusion: The results showed that 177Lu-trastuzumab could be considered as a possible new radiopharmaceutical agent for use in radioimmunotherapy of breast cancer in humans. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: In the present study, Herceptin was labeled with lutetium-177 via DOTA, and the necessary preclinical quality control tests (in vitro and in vivo) were performed to evaluate its use as a radioimmunotherapy agent. Material and Methods: Herceptin was conjugated to DOTA as a chelator in three different conjugation buffers (ammonium acetate, carbonate and HEPES buffer); each of the resulting conjugates was compared with respect to in vitro characteristics such as number of chelates per antibody, incorporated activity, immunoreactivity and in vitro stability in PBS buffer and blood serum. The biodistribution study and gamma camera imaging were performed in mice bearing breast tumors. To assess the therapeutic effects of 177Lu-Herceptin, cytotoxicity was investigated for 7 days in a SKBr3 breast cancer cell line. Results: Carbonate buffer was the best conjugation buffer (number of chelates per antibody: 6; incorporated activity: 81%; immunoreactivity: 87%; buffer stability: 86%; serum stability: 81%, after 4 days). The efficient tumor uptake observed in the biodistribution studies was consistent with the gamma camera image results. At a concentration of 4 μg ml−1, 177Lu-Herceptin (surviving cells: 5±0.6% of the total cells) of the total cells corresponded to an approximately eightfold increase in cytotoxicity in comparison to unmodified Herceptin (surviving cells: 43±3.9%). Conclusion: The new complex described herein could be considered for further evaluation in animals and potentially in humans as a radiopharmaceutical for use in the radioimmunotherapy of breast cancer. These results may be important for patients who cannot tolerate the therapeutic dosage of Herceptin currently used because of heart problems. [Copyright &y& Elsevier]

Abstract: Aim: Trastuzumab is a monoclonal antibody that is used in treating breast cancer. We labeled this monoclonal antibody with lutetium-177 and performed in vitro quality control tests as a first step in the production of a new radiopharmaceutical. Material and Methods: Trastuzumab was labeled with lutetium-177 using DOTA as chelator. Radiochemical purity and stability in buffer and human blood serum were determined using thin layer chromatography. Immunoreactivity and toxicity of the complex were tested on MCF7 breast cancer cell line. Results: The radiochemical purity of the complex was 96±0.9%. The stabilities in phosphate buffer and in human blood serum at 96 h postpreparation were 93±1.2% and 85±3.5%, respectively. The immunoreactivity of the complex was 89±1.4%. At a concentration of 1 nM, the complex killed 70±3% of MCF7 cells. At 1.9 nM, 90±5% of the cells were killed. Conclusions: The results showed that the new complex could be considered for further evaluation in animals and possibly in humans as a new radiopharmaceutical for use in radioimmunotherapy against breast cancer. [Copyright &y& Elsevier]

Abstract: In this study, we labeled trastuzumab with 177Lu to synthesize a new radiopharmaceutical for therapy of breast cancer and at the first stage investigated its therapeutic effects on SKBr3 and MCF7 breast cancer cell lines. Trastuzumab-177Lu showed very good in-vitro characteristics such as high radiochemical purity (91±0.9%), good stability in PBS buffer (86±2.3%) and blood serum (81±2.7%) up to 96h, appropriate immunoreactivity (85.4±1.1%) and high cytotoxicity in HER2 expression cells. 5 fold increase in toxicity of trastuzumab-177Lu was observed when compared with unlabeled trastuzumab on SKBr3 cells. [ABSTRACT FROM AUTHOR]

Objective: A pulmonary embolism is partial obstruction of the pulmonary artery or one of its branches by a blood clot. The early detection of this disease is very important to save the patient. The proper detection method for embolism is lung perfusion scintigraphy with nuclear medicine system, performed by 99mTc- albumin macro-aggregated (MAA) that are radiolabeled particles. There are some difficulties in synthesizing of the particles and imaging with them has some that we used chitosan microparticles as an alternative choice. Material and Methods: The chitosan particles were synthesized by ionotropic gelation method and radiolabeled with 99mTc after Purification. The quality control tests including determining particles size, labeling efficiency, stability in saline buffer, biodistribution and imaging study in the mice were performed. Results: The size of particles was 10-60 micron. The labeling efficiency: 95±4%, the good stability in saline buffer and high accumulation of activity in mice lung were seen. The slow excretion activity was observed in the lungs of mice after15 minutes. Conclusion: The results showed that the 99mTc-Chitosan microparticles might be considered as a promising radiopharmaceutical of lung perfusion scintigraphy that needs more investigations in future. [ABSTRACT FROM AUTHOR]

NHL is the most common hematologic cancer in adults. Rituximab is the FDA approved treatment of relapsed or refractory low grade B-cell Non-Hodgkin Lymphoma (NHL). But patients eventually become resistant to rituximab. Since lymphocytes and lymphoma cells are highly radiosensitive, low grade NHL that has relapsed or refractory to standard therapy is treated by RIT in which a beta-emitting radionuclide coupled to anti-CD20 antibody. The association of beta emitter radionuclide to rituximab enhances its therapeutic efficacy. The cells which lack antigen or cells which cannot be reached due to poor vascularization and intratumoral pressure in a bulky tumor would be irradiated and killed by cross fire effect of beta emitter. 90 Y, a pure high energy β-emitter with a half-life of 64 h, a maximum energy of 2.28 MeV, and maximum board of 11.3 mm in tissue is radionuclide of choice for radioimmunotherapy of outpatient administration. In this study, rituximab was conjugated to DOTA and radiolabeled with 90 YCl 3 . The stability, affinity, and immunoreactivity of radiolabeled antibody was determined in vitro and the conditions were optimized. Biodistribution studies were done in normal mice. The optimum conditions of conjugation and radiolabeling was 1-2 h at 37 °C and 1 h at 45 °C, respectively. Results showed approximately 4 DOTA molecules conjugated per antibody molecule. The purified antibody was stable and intact over 6 months stored at -20 °C. The result of immunoreactivity (≈70%), affinity (≈3 nM) and biodistribution in normal mice are acceptable.

Introduction: Herceptin is an expensive humanized antibody used for the treatment of early-stage breast cancers. This antibody can cause cardiotoxicity in some patients. In this study, we evaluated the possibility of increasing the therapeutic efficacy of Herceptin by combining magnetic nanoparticles and a permanent magnet for more accumulation in the tumor site., Methods: Herceptin magnetic nanoparticles (HMNs) were synthesized and some of their characteristics, such as stability, magnetization, particle size by transmission electron microscopy (TEM), and dynamic light scattering (DLS) technique, were measured. The biodistribution study was checked in mice bearing breast tumor with and without a permanent magnet on the position of the tumor. The therapeutic effects of HMNs were considered in this condition., Results: The size distribution of HMNs determined by the DLS technique was 182±7 nm and the average size by TEM was 100±10 nm. The reductions of 81% and 98% in the mean tumor volume for the group that received HMNs with magnetic field were observed at 42 and 45 days after injection, respectively., Conclusion: The good results in mice indicated that Herceptin-loaded iron oxide nanoparticles with external magnetic field have good potential for use in humans as a targeted drug delivery that needs more investigation.

Objective: Estimation of activity accumulated in tumor and organs is very important in predicting the response of radiopharmaceuticals treatment. In this study, we synthesized (177)Lutetium ((177)Lu)-trastuzumab-iron 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: (177)Lu-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 (177)Lu-trastuzumab-iron oxide nanoparticles could be used as a double radiopharmaceutical agent in mice bearing tumor. Results showed that (177)Lu-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.

Background: We aimed to determine specific formulae by which we are able to estimate the body stature from the length of ulna and tibia calculated from the X-rays in order to be a reference for skeletal remains-based identification in Iranian population., Methods: The length of right ulna and tibia of 49 male and 52 female adults, who were anatomically healthy, were measured on the antero-posterior X-rays. Body height of each subject was also recorded., Results: Mean stature of the male and female adults was reported to be 171 ± 3.6 and 160 ± 3.9 centimeters (cm), respectively. Four single linear regression equations and 2 multiple regression equations were obtained., Conclusions: Lengths of ulna and tibia measured on the X-rays may be useful for estimation of the stature in cases of forensic personal identification., Keywords: stature - length of long bones - ulna - tibia - radiological evaluation - skeletal remains.