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Bispecific Antibody Pretargeting of Radionuclides for Immuno–Single-Photon Emission Computed Tomography and Immuno–Positron Emission Tomography Molecular Imaging: An Update

Authors' Affiliations: ¹ Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, New Jersey; and ² Immunomedics, Inc., and ³ IBC Pharmaceuticals, Inc., Morris Plains, New Jersey

Requests for reprints: Robert M. Sharkey, Garden State Cancer Center, Center for Molecular Medicine and Immunology, 520 Belleville Avenue, Belleville, NJ. Phone: 973-844-7121; Fax: 973-844-7120; E-mail: rmsharkey{at}gscancer.org.

Molecular imaging is intended to localize disease based on distinct molecular/functional characteristics. Much of today's interest in molecular imaging is attributed to the increased acceptance and role of ¹⁸F-flurodeoxyglucose (¹⁸F-FDG) imaging in a variety of tumors. The clinical acceptance of ¹⁸F-FDG has stimulated research for other positron emission tomography (PET) agents with improved specificity to aid in tumor detection and assessment. In this regard, a number of highly specific antibodies have been described for different cancers. Although scintigraphic imaging with antibodies in the past was helpful in patient management, most antibody-based imaging products have not been able to compete successfully with the sensitivity afforded by ¹⁸F-FDG-PET, especially when used in combination with computed tomography. Recently, however, significant advances have been made in reengineering antibodies to improve their targeting properties. Herein, we describe progress being made in using a bispecific antibody pretargeting method for immuno–single-photon emission computed tomography and immunoPET applications, as contrasted to directly radiolabeled antibodies. This approach not only significantly enhances tumor/nontumor ratios but also provides high signal intensity in the tumor, making it possible to visualize micrometastases of colonic cancer as small as 0.1 to 0.2 mm in diameter using an anti–carcinoembryonic antigen bispecific antibody, whereas FDG failed to localize these lesions in a nude mouse model. Early detection of micrometastatic non–Hodgkin's lymphoma is also possible using an anti-CD20–based bispecific antibody pretargeting procedure. Thus, this bispecific antibody pretargeting procedure may contribute to tumor detection and could also contribute to the detection of other diseases having distinct antigen targets and suitably specific antibodies.