Affiliations: [a] Department of Clinical Biochemistry, School of Medical Sciences, Tarbiat Modarres University, Tehran, Iran | [b] Department of Radioisotope, Nuclear Research Center, Atomic Energy Organization of Iran, Tehran, Iran | [c] Department of Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran | [d] Department of Immunology, School of Medical Sciences, Tarbiat Modarres University, Tehran, Iran | [e] Department of Biology, Faculty of Sciences, Islamic Azad University Zanjan, Branch Zanjan, Iran | [f] Cardiovascular Research Center, Shahid Rajaee Hospital, Tehran, Iran
Correspondence:
[*]
Corresponding author: M.J. Rasaee, Department of Clinical Biochemistry, School of Medical Sciences, Tarbiat Modarres University, Tehran, Iran. Fax: +98 21 8013030; E-mail: [email protected].
Abstract: PR81 is a monoclonal antibody that binds with high affinity to MUC1, which is over expressed on breast and other tumors. The objective of this study was to evaluate the application of this antibody against MUC1 as a radioimmunotherapeutical agent. Monoclonal antibody (PR81) against MUC1 was prepared, characterized, purified, and labeled with 131I. The immunoreactivity of radiolabeled mAb PR81with MUC1 (the native protein), BSA-P20 (a 20 amino acid corresponding the tandem repeat of MUC1) and MCF7 cell line were performed by RIA. In vitro stability of radiolabeled mAb in human serum was determined by thin layer chromatography (TLC). Cell toxicity and in vitro internalization studies were performed with the MCF7 cell line, and the tissue biodistribution of the radioiodinated PR81 was evaluated in normal BALB/c mice at 4, 24 and 48 hrs. The tumor imaging was performed in BALB/c mice with breast xenograft tumors at 24 and 72 hr after the complex injection. The labeling efficiency was found to be 59.9% ± 7.9%. MAb- 131I conjugates showed high immunoreactivity towards MUC1 protein, BSA-P20 and MCF7 cell line. In vitro stability of the labeled product in human serum was found to be more than %50 over 24 hr. Cell toxicity and in vitro internalization studies showed that the mAb-131I conjugate inhibited 80% growth of the MCF7 cultured cell lines in vitro in a high concentration and up to %60 of the conjugate internalized after 24 h. Biodistribution studies were performed in normal BALB/c mice at 4, 24 and 48 hrs post-injection and no important accumulation was observed in vital organs. The tumors were visualized with high sensitivity after 24 and 72 hr in radioimmunoscintographical studies. These results show that the new radiopharmaceutical may be considered as a promising candidate for therapy of breast cancer.
