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Abstract
Therapeutic antibodies are well established as an important class of drugs in modern medicine. The exquisite specificity and affinity for a specific target offered by antibodies has also encouraged their development as delivery vehicles for agents such as radionuclides to target tissues, for radioimmunoimaging and radioimmunotherapy. Specifically, in nuclear medicine, radionuclide-conjugated antibody molecules make it possible to image diseased loci with greater sensitivity than other imaging modalities such as magnetic resonance imaging. Furthermore, two radionuclide-conjugated antibodies have recently been approved for the therapy of non-Hodgkin’s lymphoma. However, optimal implementation of antibodies has been limited by the extended circulation persistence that is characteristic of native antibodies, which is responsible for increased background activity in radioimmunoimaging applications and dose-related normal organ toxicities in radioimmunotherapy. In this article the current status of radiolabelled intact antibodies is reviewed, focusing on strategies to improve their pharmacokinetic properties to suit a desired application. Examples from the literature that represent different approaches to accomplishing this task in terms of their successes as well as limitations, and perspectives for the future are discussed.
Acknowledgement
The authors are grateful to Jared Allen, who prepared the graphics of figure 1. Also we would like to thank the numerous colleagues and collaborators who have worked in the fields of antibody engineering and immunoconjugation over the years. We apologise to any authors whose work has not been acknowledged in this review due to space limitation. Work in Anna Wu’s laboratory was supported by National Institute of Health grants CA43904, CA86306, CA92131 and Department of Defense grants 17-00-1-150 and DAMD 17-00-1-203.