PMID: 9443740Jan 27, 1998Paper

Tumor pretargeting for radioimmunodetection and radioimmunotherapy

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
H ZhuL T Baxter

Abstract

The limited success of the sole use of monoclonal antibodies for cancer detection and treatment has led to the development of multistep methods using antibodies in conjunction with low molecular weight agents. For tumor pretargeting, it is important to optimize dose and schedule of relevant agents and to understand barriers to targeted delivery. Here, we address these issues for the anti-carcinoembryonic antigen bifunctional antibody-hapten and the streptavidinylated antibody-biotin systems using a recently developed physiologically based pharmacokinetic model. For baseline conditions of a standard 70-kg man with a 20-g tumor embedded in the liver, the model was used in conjunction with the Medical Internal Radiation Dosimetry schema to: estimate absorbed doses in tumor and normal tissues; determine the dose dependence of effector agent accumulation in tumor; simulate tumor-to-background effector agent uptake ratio; and calculate the therapeutic ratio for different antibody forms and radionuclides. Alternative drug administration schemes and variable tumor physiological conditions were considered. Model simulations showed that 131I-labeled biotin with the streptavidinylated F(ab')2 provided the highest therapeutic ratio under t...Continue Reading

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