BREAST-CANCER IMAGING WITH RADIOLABELED PEPTIDE FROM COMPLEMENTARITY-DETERMINING REGION OF ANTITUMOR ANTIBODY

Specific tumour imaging with radiolabelled monoclonal antibodies has b een extensively investigated. Although some success has been reported, there are many limitations due to the slow kinetics, poor extravasati on, catabolism by the reticuloendothelial system, and nonspecific upta ke of macromolecules such as antibodies. We have tried to overcome som e of the problems associated with monoclonal antibodies while retainin g their specificity by using an antibody-derived synthetic peptide. A synthetic pentadecapeptide (alpha M2) derived from the third heavy-cha in complementarity-determining region (CDR-3H) of a tumour-associated monoclonal antibody was produced and shown to retain its specificity a gainst the pan-carcinoma cell-surface antigen, polymorphic epithelial mucin, detected by the parent antibody. The peptide was radiolabelled with technetium-99m and injected intravenously to image malignant lesi ons in 26 women with primary, recurrent, or metastatic breast cancer. Visualisation of breast tumours and their metastases was obtained shor tly after administration of alpha M2, and was optimum by 3 h. Overall, 57 (77%) of 74 sites were visualised. Successful imaging was achieved in 14 of 15 primary tumour sites and all of eight local recurrences. Five of six metastases in the opposite breast, eight of 15 metastatic axillary lymph nodes, and all of six metastatic supraclavicular lymph nodes were imaged. Metastatic sites in the lungs, mediastinum, chest w all, and liver were poorly visualised because of background cardiac bl ood pool, alpha M2 detected small lesions (<2 cm) as efficiently as la rger ones. The peptide was rapidly (3 h) cleared from the circulation. No acute or chronic adverse reactions due to the alpha M2 were observ ed. Specific tumour targeting with the radiolabelled anticancer peptid e alpha M2 offers new opportunities for breast cancer imaging and poss ibly therapy.