Development of [64 Cu]-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 with64 Cu followed by radiochemical purity, in vitro stability, in vitro internalization and immunoreactivity determination. The tissue biodistribution of the64 Cu-DOTA-PR81 and64 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. The64 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 that64 Cu-DOTA-PR81 may be considered as a potential PET tracer for diagnosis and follow-up of MUC1 expression in oncology.