1. Preparation and biological evaluation of (177)Lu conjugated PR81 for radioimmunotherapy of breast cancer.
- Author
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Salouti M, Babaei MH, Rajabi H, and Rasaee Mj
- Subjects
- Animals, Antibodies, Monoclonal immunology, Antibodies, Monoclonal pharmacokinetics, Antibodies, Monoclonal toxicity, Breast Neoplasms diagnostic imaging, Breast Neoplasms immunology, Breast Neoplasms metabolism, Cell Line, Tumor, Female, Heterocyclic Compounds, 1-Ring chemistry, Humans, Mice, Mice, Inbred BALB C, Quality Control, Radioimmunodetection, Antibodies, Monoclonal therapeutic use, Breast Neoplasms radiotherapy, Lutetium therapeutic use, Radioimmunotherapy methods, Radioisotopes therapeutic use
- Abstract
Aim: PR81 is a monoclonal antibody that binds with high affinity to MUC1 antigen that is over expressed in 80% of breast cancers. In this study, we developed a method for indirect labeling of PR81 with lutetium-177 and performed all preclinical qualifications in production of a biologic agent for radioimmunotherapy of breast cancer., Materials and Methods: The radiochemical purity and in vitro stability of (177)Lu labeled PR81 was determined by instant thin layer chromatography. The immunoreactivity and cell toxicity of the complex were tested on MCF7 cell line. The biodistribution and scintigraphy studies were performed in BALB/c mice with breast tumor., Results: The radiochemical purity was 91.2±3.8% after 2 h. The in vitro stabilities in phosphate buffer and human blood serum were 83.1±3.4% and 76.2±3.6% at 96 h, respectively. The immunoreactivity of the complex was 83.4±2.4%. The cell toxicity study showed that the complex inhibited 85.2±3.4% growth of MCF7 cells at a concentration of 2500 ng/ml after 96 h. The biodistribution and scintigraphy studies showed the accumulation of the complex at the site of tumors with high sensitivity and specificity., Conclusion: The results showed that one may consider (177)Lu-DOTA-PR81 as a potential radiopharmaceutical for therapy of human breast cancer, which needs further investigations., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
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