Tailoring antibodies for radionuclide delivery.
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.
Kenanova
Vania
V
Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California-Los Angeles, 700 Westwood Plaza, Los Angeles, CA 90095, USA.
Wu
Anna M
AM
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D006801:Humans; D007128:Immunoglobulin Fragments / Q000627:therapeutic use*; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000532:radiotherapy*; D016719:Radioimmunodetection / Q000379:methods; D016499:Radioimmunotherapy / Q000379:methods; D011868:Radioisotopes / Q000627:therapeutic use
D000906:Antibodies; D000970:Antineoplastic Agents; D007128:Immunoglobulin Fragments; D011868:Radioisotopes