Radiolabeling of Antibodies for Therapy and Diagnosis
Radioimmunotherapeutic and radioimmunodiagnostic procedures have been the subjects of nearly 200 clinical trials since 1978. Applications range from diagnosis of tumor deposits to systemic radiation therapy. Originally, murine IgG was the most common antibody form used clinically. Later the antibody fragments, Fab and F(ab’)2 , were extensively investigated as the alternative radioisotope carriers displaying more favorable pharmacokinetics. Future clinical applications will include products of molecular engineering, such as single-chain antigen-binding proteins, “humanized” (also known as “chimeric”) antibodies, human antibodies, and bifunctional antibodies. Selection of antibodies for clinical trials is an extensive and detailed process. The factors to be considered include characterization of the antibody with regard to its interactions with the antigen(s) of interest, nonspecific binding to non-target tissues, and in vivo pharmacokinetics. In addition, the biological consequences of chemical modifications made during production of the radiolabeled material must be assessed. Ideally, the choice of the radioisotope and radiolabeling methods is individually tailored for each antibody to yield products that display minimally impaired biological properties for any given application. Only seldom can such a detailed approach be afforded. Thus, prior experiences with antibodies and radioisotopes described in the literature are useful in designing the experimental strategies. For each of the commonly used radioisotopes, there are several well-tested methods. A brief overview of available methodologies and specific procedures for radiolabeling with radiometals is given in the following sections.
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