Radioimmunoscintigraphy of Breast Tumor Xenografts in Mouse Model by 99mTc Direct Radiolabeling of a Monoclonal Antibody PR81
نویسندگان
چکیده مقاله:
Introduction: The radioimmunoscintigraphy (RIS) has found widespread clinical applications in tumor diagnosis. Human epithelial mucin, MUC1, is commonly over expressed in adenocarcinoma including 80% of breast cancers and represents a useful target for RIS. The PR81 is a new murine anti-MUC1 monoclonal antibody that was found to react with the membrane extracts of several human breast cancerous tissues and the cell surface of some MUC1 positive cell lines. In this study, a direct method which is very simple, rapid and efficient for the labeling of this MAb with 99mTc, particularly suitable for the development of a ‘kit’, was developed. The quality control of new radiopharmaceutical and immunoscintigraphy studies in BALB/c mice bearing breast tumor xenografts were also performed. Materials and Methods: The Ab reduction was performed with 2-mercaptoethanol (2-ME) at a molar ratio of 2000:1 (2-ME:MAb) and reduced Ab was labeled with 99mTc via methylene diphosphonate (MDP) as a transchelator. The labeling efficiency was determined by ITLC. The amount of radiocolloids was measured by cellulose nitrate electrophoresis. The stability of the labeled product was checked in fresh human serum by gel filtration chromatography (FPLC) over 24 hrs. The integrity of the labeled MAb was checked by the means of SDS-PAGE. Cell-binding assay was used to test the binding ability of 99mTc-PR81 to MCF7 cells. Biodistribution was studied in normal BALB/c mice at 4 and 24 hrs post-injection. The tumor imaging was performed in female BALB/c mice with breast tumor xenografts 24 hrs after the new complex injection. Results: The labeling efficiency was 94.2%±2.3 and radiocolloids were 2.5%±1.7. In vitro stability was 70%±5.7 in fresh human serum over 24 hrs. There was no significant Ab fragmentation due to the labeling procedure. Both the labeled and unlabeled PR81 were able to compete for binding to MCF7 cells. The biodistribution studies in normal BALB/c mice showed that there was no important accumulation in any organ. The immunoscintigraphy studies demonstrated definite localization of the preparation at the site of tumors with high sensitivity. Discussion and Conclusion: The results show that by using the Schwarz method of radiolabeling MAb PR81, a labeling yield higher than 90% with high stability of the complex in human serum can be obtained. These findings demonstrated that the new radiopharmaceutical can be considered as a promising candidate for imaging of human breast cancer.
منابع مشابه
radioimmunoscintigraphy of breast tumor xenografts in mouse model by 99mtc direct radiolabeling of a monoclonal antibody pr81
introduction: the radioimmunoscintigraphy (ris) has found widespread clinical applications in tumor diagnosis. human epithelial mucin, muc1, is commonly over expressed in adenocarcinoma including 80% of breast cancers and represents a useful target for ris. the pr81 is a new murine anti-muc1 monoclonal antibody that was found to react with the membrane extracts of se...
متن کامل99mTc Direct radiolabeling of PR81, a new anti-MUC1 monoclonal antibody for radioimmunoscintigraphy
Introduction: Monoclonal antibodies labeled mainly with 99mTc are being widely used as imaging agents in nuclear medicine. Recently PR81 was introduced as a new murine anti-MUC1 MAb against human breast carcinoma. This antibody reacts with the tandem repeat of 20-mer peptide of protein backbone, and is of IgG1 class, with an affinity of 2.19×10-8 M-1. Due to high sp...
متن کامل99mtc direct radiolabeling of pr81, a new anti-muc1 monoclonal antibody for radioimmunoscintigraphy
introduction: monoclonal antibodies labeled mainly with 99mtc are being widely used as imaging agents in nuclear medicine. recently pr81 was introduced as a new murine anti-muc1 mab against human breast carcinoma. this antibody reacts with the tandem repeat of 20-mer peptide of protein backbone, and is of igg1 class, with an affinity of 2.19×10-8 m-1. due to high specific reactivity, this antib...
متن کاملRadiolabeling of Ceftriaxone with 99mTc as a Targeting Radiopharmaceutical for Staphylococcus Aureus Detection in Mouse Model
Introduction Bacterial infection is one of the major causes of morbidity and mortality especially in developing countries. Nuclear medicine has an important role in helping the diagnosis of deep-seated infections by developing more specific radiopharmaceuticals. The aim of this study was to evaluate 99mTc-labeling ceftriaxone as a new radiopharmaceutical for Staphylococcus aureus infection imag...
متن کاملMonoclonal Antibody Production Against Vimentin by Whole Cell Immunization in a Mouse Model
Background: Pancreatic carcinoma is the fourth-leading cause of cancer death in the United States and due to its late presentation, only few patients would be candidates for the curative treatment of pancreactomy. Monoclonal antibodies have brought hope to targeted therapy.Objectives: To identify new biomarkers, a panel of monoclonal antibodies was genera...
متن کاملEvaluation of a 99mTc-tricine Vascular Disrupting Agent as an In-vivo Imaging in 4T1 Mouse Breast Tumor Model
Colchicine as a vascular disrupting agent creates microtubule destabilization whichinduces vessel blockage and consequently cell death. Accordingly, colchicines and itsanalogues radiolabeled with 99mTc may have potential for visualization of tumor. In this work,deacetylcolchicine a colchicine analogue was labeled with 99mTc via tricine as a coligandand characterized for its tumor targeting prop...
متن کاملمنابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ذخیره در منابع من قبلا به منابع من ذحیره شده{@ msg_add @}
عنوان ژورنال
دوره 2 شماره 3
صفحات 45- 52
تاریخ انتشار 2005-09-01
با دنبال کردن یک ژورنال هنگامی که شماره جدید این ژورنال منتشر می شود به شما از طریق ایمیل اطلاع داده می شود.
میزبانی شده توسط پلتفرم ابری doprax.com
copyright © 2015-2023