title: A pretargeting system for tumor PET imaging and radioimmunotherapy.
abstract: Labeled antibodies, as well as their fragments and antibody-derived recombinant constructs, have long been proposed as general vectors to target radionuclides to tumor lesions for imaging and therapy. They have indeed shown promise in both imaging and therapeutic applications, but they have not fulfilled the original expectations of achieving sufficient image contrast for tumor detection or sufficient radiation dose delivered to tumors for therapy. Pretargeting was originally developed for tumor immunoscintigraphy. It was assumed that directly-radiolabled antibodies could be replaced by an unlabeled immunoconjugate capable of binding both a tumor-specific antigen and a small molecular weight molecule. The small molecular weight molecule would carry the radioactive payload and would be injected after the bispecific immunoconjugate. It has been demonstrated that this approach does allow for both antibody-specific recognition and fast clearance of the radioactive molecule, thus resulting in improved tumor-to-normal tissue contrast ratios. It was subsequently shown that pretargeting also held promise for tumor therapy, translating improved tumor-to-normal tissue contrast ratios into more specific delivery of absorbed radiation doses. Many technical approaches have been proposed to implement pretargeting, and two have been extensively documented. One is based on the avidin-biotin system, and the other on bispecific antibodies binding a tumor-specific antigen and a hapten. Both have been studied in preclinical models, as well as in several clinical studies, and have shown improved targeting efficiency. This article reviews the historical and recent preclinical and clinical advances in the use of bispecific-antibody-based pretargeting for radioimmunodetection and radioimmunotherapy of cancer. The results of recent evaluation of pretargeting in PET imaging also are discussed.
authors: Nuclear Medicine Department, Nantes University Hospital Nantes, France ; Nuclear Medicine Department, Institut de Cancérologie de l'Ouest René Gauducheau Nantes, France ; Cancer Research Center, University of Nantes, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique Nantes, France.
authors: Françoise
authors: F
authors: Kraeber-Bodéré
authors: Nuclear Medicine Department, Institut de Cancérologie de l'Ouest René Gauducheau Nantes, France ; Cancer Research Center, University of Nantes, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique Nantes, France.
authors: Caroline
authors: C
authors: Rousseau
authors: Nuclear Medicine Department, Nantes University Hospital Nantes, France ; Cancer Research Center, University of Nantes, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique Nantes, France.
authors: Caroline
authors: C
authors: Bodet-Milin
authors: Cancer Research Center, University of Nantes, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique Nantes, France ; Radiology Department, Nantes University Hospital Nantes, France.
authors: Eric
authors: E
authors: Frampas
authors: Nuclear Medicine Department, Nantes University Hospital Nantes, France ; Cancer Research Center, University of Nantes, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique Nantes, France.
authors: Alain
authors: A
authors: Faivre-Chauvet
authors: Nuclear Medicine Department, Institut de Cancérologie de l'Ouest René Gauducheau Nantes, France ; Cancer Research Center, University of Nantes, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique Nantes, France.
authors: Aurore
authors: A
authors: Rauscher
authors: Immunomedics, Inc. Morris Plains, NJ, USA.
authors: Robert M
authors: RM
authors: Sharkey
authors: Immunomedics, Inc. Morris Plains, NJ, USA ; Garden State Cancer Center, Center for Molecular Medicine and Immunology Morris Plains, NJ, USA.
authors: David M
authors: DM
authors: Goldenberg
authors: GIP Arronax Saint-Herblain, France.
authors: Jean-François
authors: JF
authors: Chatal
authors: Cancer Research Center, University of Nantes, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique Nantes, France ; GIP Arronax Saint-Herblain, France.
authors: Jacques
authors: J
authors: Barbet
keywords: bispecific antibody; immuno-PET; immunoscintigraphy; pretargeting; radioimmunotherapy