Breast cancer imaging with radiolabelled peptide from complementarity-determining region of antitumour antibody.
Specific tumour imaging with radiolabelled monoclonal antibodies has been extensively investigated. Although some success has been reported, there are many limitations due to the slow kinetics, poor extravasation, catabolism by the reticuloendothelial system, and non-specific uptake of macromolecules such as antibodies. We have tried to overcome some of the problems associated with monoclonal antibodies while retaining their specificity by using an antibody-derived synthetic peptide. A synthetic pentadecapeptide (alpha M2) derived from the third heavy-chain complementarity-determining region (CDR-3H) of a tumour-associated monoclonal antibody was produced and shown to retain its specificity against 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 lesions in 26 women with primary, recurrent, or metastatic breast cancer. Visualisation of breast tumours and their metastases was obtained shortly 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 wall, and liver were poorly visualised because of background cardiac blood pool. alpha M2 detected small lesions ( < 2 cm) as efficiently as larger ones. The peptide was rapidly (3 h) cleared from the circulation. No acute or chronic adverse reactions due to the alpha M2 were observed. Specific tumour targeting with the radiolabelled anticancer peptide alpha M2 offers new opportunities for breast cancer imaging and possibly therapy.
Sivolapenko
G B
GB
Encephalos Research and Therapeutic Institute, Athens, Greece.
Douli
V
V
Pectasides
D
D
Skarlos
D
D
Sirmalis
G
G
Hussain
R
R
Cook
J
J
Courtenay-Luck
N S
NS
Merkouri
E
E
Konstantinides
K
K
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D001943:Breast Neoplasms / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D007553:Isotope Labeling; D008207:Lymphatic Metastasis / Q000000981:diagnostic imaging; D008875:Middle Aged; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis / Q000000981:diagnostic imaging; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging; D010455:Peptides / Q000276:immunology*; D011877:Radionuclide Imaging; D013667:Technetium
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D007135:Immunoglobulin Variable Region; D010455:Peptides; D013667:Technetium