Radioimmunotherapy of Solid Tumors: A Review "Of Mice and Men"

Abstract

Radioimmunotherapy in lymphoma is crossing the threshold to become a standard mode of treatment. Whereas in solid tumors in preclinical studies, radioimmunotherapy has proven to be superior to conventional chemotherapy, clinical success is still limited. The purpose of this brief review is to analyze recent developments in preclinical as well as clinical radioimmunotherapy of solid, CEA-expressing tumors. Advances in experimental radioimmunotherapy are characterized by the development of metastatic, rather than subcutaneous, tumor models in nude mice, which seem to reflect the actual clinical situation much more accurately. Furthermore, the recent development of strategies to reduce the renal accretion of antibody fragments and peptides enables the use of such smaller molecules for therapy, especially those also labeled with radiometals and other forms of intracellularly retained radionuclides. Recent developments in clinical radioimmunotherapy are characterized by a trend toward the treatment of small-volume and micrometastatic disease, as is the case, e.g., in adjuvant settings. Interestingly, despite dramatic differences in size, weight and percent-of-injected-dose-per-gram uptake values, only small differences between animal models and the actual patient situation exist with respect to activity concentrations (in μCi/gram) in the tumors and tissues. Because the activity concentration over time determines the radiation absorbed dose, and thus biological effects, we postulate that animal models should be able to predict actual clinical scenarios fairly well. These findings could be used as guidelines in the design of future preclinical, as well as clinical, trials.