title: Development of [⁶⁴Cu]-DOTA-PR81 radioimmunoconjugate for MUC-1 positive PET imaging.
abstract: OBJECTIVE
  Breast cancer radioimmunoscintigraphy targeting MUC1 expression is a growing field of work in nuclear medicine research. PR81 is a monoclonal antibody that binds with high affinity to MUC1, which is over expressed on breast tumors. In this study, we report production, quality control and preclinical qualifications of a copper-64 labeled PR81 for PET imaging of breast cancer.
  
  
  METHODS
  PR81 was conjugated with DOTA-NHS-ester and purified by molecular filtration followed by chelate:mAb ratio determination by spectrophotometric method. DOTA-PR81 was labeled with (64)Cu followed by radiochemical purity, in vitro stability, in vitro internalization and immunoreactivity determination. The tissue biodistribution of the (64)Cu-DOTA-PR81 and (64)Cu-DOTA-hIgG was evaluated in BALB/c mice with breast carcinoma tumors using tissue counting and imaging.
  
  
  RESULTS
  The radiochemical purity of radioimmunoconjugate was >95±1.9% (ITLC) (specific activity; 4.6 μCi/μg). The average number of chelators per antibody was 3.4±0.3:1. The (64)Cu-DOTA-PR81 showed immunoreactivity towards MUC1 antigen and MCF7 cell line with significant in vitro stability (>89% in PBS and 78±0.5% in human serum) over 48 h. Maximum internalized activity of radiolabeled PR81 in 4-8 h was 81.5%. The biodistribution and scintigraphy studies showed the accumulation of the complex at the site of tumors with high sensitivity and specificity compared to control probes.
  
  
  CONCLUSIONS
  The results showed that (64)Cu-DOTA-PR81 may be considered as a potential PET tracer for diagnosis and follow-up of MUC1 expression in oncology.
authors.affiliation: Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), 11365-3486, Tehran, Iran.
authors.forename: Behrouz
authors.initials: B
authors.lastname: Alirezapour
authors.affiliation: Department of Clinical Biochemistry, School of Medical Sciences, Tarbiat Modares University (TMU), Tehran, Iran.
authors.forename: Mohammad Javad
authors.initials: MJ
authors.lastname: Rasaee
authors.affiliation: Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), 11365-3486, Tehran, Iran. Electronic address: ajalili@aeoi.org.ir.
authors.forename: Amir Reza
authors.initials: AR
authors.lastname: Jalilian
authors.affiliation: Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), 11365-3486, Tehran, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Rajabifar
authors.affiliation: Department of Life Science Engineering, Faculty of New Sciences & Technologies, University of Tehran, Tehran, Iran.
authors.forename: Javad
authors.initials: J
authors.lastname: Mohammadnejad
authors.affiliation: Department of Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Malihe
authors.initials: M
authors.lastname: Paknejad
authors.affiliation: Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), 11365-3486, Tehran, Iran.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Maadi
authors.affiliation: Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), 11365-3486, Tehran, Iran.
authors.forename: Sedigheh
authors.initials: S
authors.lastname: Moradkhani
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D001692:Biological Transport; D016466:CHO Cells; D045744:Cell Line, Tumor; D003301:Copper Radioisotopes; D006224:Cricetinae; D003412:Cricetulus; D055808:Drug Discovery; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry* / Q000378:metabolism; D007553:Isotope Labeling; D061986:MCF-7 Cells; D051379:Mice; D018396:Mucin-1 / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D055550:Protein Stability; D011854:Radiochemistry; D016719:Radioimmunodetection; D013388:Succinimides / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D003301:Copper Radioisotopes; C502492:DOTA-NHS; D018796:Immunoconjugates; D018396:Mucin-1; D013388:Succinimides
keywords: Biodistribution; Breast carcinoma; Copper-64; Imaging; MUC1; PR81