Basis of antibody imaging and therapy

Immunologically derived molecules for use in radioimmunotargeting are rapidly evolving from whole murine-derived antibodies to novel recombinant molecules. In the age of antibody engineering, it is important to understand the various physiologic factors which dictate behavior of these constructs. When evaluating a molecule for immunological targeting, issues of importance include affinity of binding, density and distribution of the antigen, and valence of the molecule, which together affect avidity. Size of the targeting molecule is important in that smaller molecules have potentially increased tissue penetration, reduced immunogenicity, and accelerated clearance from blood and background, but also exhibit decreased bioavailability, and potentially altered excretion pathways which may obscure areas of interest. Incorporation of foreign protein sequences, derived from other species, into the targeting molecule may lead to immunization of the host and altered biodistribution but can potentially be circumvented by recombinant DNA techniques. Identifying extremely high-affinity antibodies, which was once the holy grail of radioimmunotargeting, is now believed to be of more selected benefit, depending on valence, presence and density of antigen on target and background tissues, and the need for homogeneous targeting of the tumor, as in therapy applications. The field of radioimmunotargeting is evolving from the use of whole or fragmented murine antibodies for antibody imaging to development of novel engineered molecules for therapy and imaging applications. Understanding the physiologic behavior of immunologically derived molecules is therefore of ever-growing importance to the nuclear medicine practitioner.