Radioimmunoscintigraphy of Breast Tumor Xenografts in Mouse Model by 99mTc Direct Radiolabeling of a Monoclonal Antibody PR81

Salouti, M. and Rajabi, H. and Babaei, H. and Rasaee, M.J. and Najafi, R. and Mazidi, M. and Shafiee, M. and Hasan, Z. M. and Bitarafan Rajabi, A. and Mohammad nejad, J. and Altarihi, T.M. and Namvar, N. (2005) Radioimmunoscintigraphy of Breast Tumor Xenografts in Mouse Model by 99mTc Direct Radiolabeling of a Monoclonal Antibody PR81. Iranian Journal of Medical Physics, 2 (3). pp. 45-52.

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Abstract

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 â��kitâ��, 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.Â

Item Type: Article
Subjects: WN Radiology . Diagnostic Imaging
Divisions: Journals > Iranian J Medical Physics
Depositing User: ijmp ijmp
Date Deposited: 21 Jan 2018 15:46
Last Modified: 21 Jan 2018 15:46
URI: http://eprints.mums.ac.ir/id/eprint/9011

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