Preparation and preliminary studies of [64Cu]-antiMUC-1 for breast cancer targeting

Monoclonal antibodies (mAb) have been applied for radioimmunoscintigraphy of breast cancer (1) and are within the important categories of molecules used in targeted therapy of cancers (2). An ideal antibody for radioimmunoscintigraphy should target an antigen that is tumorspecific, generously expressed on all the cancer cells and is not shed into the blood circulation (3). MUC1 is high molecular weight glycoprotein as an antigen that is expressed on the apical membrane of the epithelial cells in the ducts and acini of the breast tissue (4,5). Cancerous MUC1 is structurally different from normal MUC1, exposing novel regions of the protein core (6). MUC1 expression causes anchorage independent growth and tumor formation, and is a useful marker for the prognosis of the patients with carcinoma (7,8). This antigen is aberrantly overexpressed in 80% of the breast cancers and is an attractive target for radioimmunotherapy and radioimmunoscintigraphy. Recently several anti-MUC1 mAbs against the human breast carcinoma has been reported for Abstract PR81 is a monoclonal antibody that binds with high affinity to MUC1 that over expressed on breast tumors. PR81 is considered a suitable targeting molecule that was radiolabeled using Cu-64 for positron imaging studies. The monoclonal antibody was conjugated with DOTA moiety and after purification was evaluated for radiochemical purity, immunoreactivity, cell toxicity and structure integrity as well as biodistribution study in normal rats. The radiolabeled antibody prepared with acceptable radiochemical purity (> 93.2 ± 0.6 %, ITLC; specific activity; 4.6 μCi/μg), protein structure integration, significant cytotoxicity and significant immunoreactivity retention was assessed by radioimmunoassay (RIA). Animal biodistribution of the 64 Cu-DOTA-PR81 was consistent with other radiolabeled antibodies. The results showed that 64 Cu-DOTA-PR81 may be considered for tumor imaging for ultimate diagnosis and follow-up of MUC1 expression in oncology.