This brief review covers the concept of pretargeted
radioimmunotherapy and summarize the results obtained in preclinical animal models and initial phase I clinical trials.
Reagents studied have been a bifunctional antibody prepared by crosslinking
Fab' fragments from two
antibodies with different specificity, one binding the target
antigen expressed on
tumors and the other binding a radiolabeled
peptide. The alternative system is a conjugate of
streptavidin linked to the pretargeting agent and radiolabeled
biotin. After reaching optimal
tumor targeting of the pretargeting agent, a synthetic mono-
biotin poly N-acetyl-
galactosamine compound was used to clear unbound targeting agent from the circulation before the injection of radiolabeled
biotin. Promising therapeutic responses were obtained in various
tumor xenograft models in athymic nude mice. A phase I study of an anti-CD20/
streptavidin pretargeting agent and 15 mCi/m(2)(90)Y-
biotin produced objective responses with minimal toxicity among
lymphoma patients, with an average
tumor-to-whole-body radiation dose ratio of 49. Pretargeting
radioimmunotherapy approaches have shown higher
tumor-to-whole-body ratios than that usually obtained with one-step
radioimmunotherapy.