Journal
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
Volume 16, Issue 6, Pages 457-467Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/10849780152752065
Keywords
antibody; linker; radioimmunotherapy
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Funding
- NCI NIH HHS [P01 CA47829] Funding Source: Medline
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Radioimmunotherapy of cancer utilizes anti-tumor antibodies or antibody fragments conjugated to radionuclides to deliver radiation selectively to tumors. However, radiolabeled proteins deposit radioactivity in normal organs that metabolize or conserve proteins and peptides, primarily liver and kidneys. To accelerate the clearance of radioactivity from normal tissues, linkers between the antibody or antibody fragment and the radioactive moiety have been designed for cleavage in the liver and kidneys, to liberate low molecular weight radioactive species for rapid excretion. Modest success in improving the tumor-to-liver and tumor-to-kidney radiation dose ratios have been achieved in preclinical studies. Such changes when taken to clinical studies have suggested useful impact on therapeutic work. Recent advances in the development of cleavable linkers are described.
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