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  • Title: Development of [⁶⁴Cu]-DOTA-PR81 radioimmunoconjugate for MUC-1 positive PET imaging.
    Author: Alirezapour B, Rasaee MJ, Jalilian AR, Rajabifar S, Mohammadnejad J, Paknejad M, Maadi E, Moradkhani S.
    Journal: Nucl Med Biol; 2016 Jan; 43(1):73-80. PubMed ID: 26453525.
    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. CONCLUSION: 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.
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