Thursday, December 5, 2013
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Assays & screens
Radiohalogen label for
improved tracking of therapeutic antibodies in vivo
radiohalogen probe with improved cell retention could aid preclinical
biodistribution studies of therapeutic mAbs. A drawback of using iodine
radionuclides to label and track mAbs is rapid diffusion of the label from
cells following endocytosis and lysosomal degradation. To improve cellular
retention of the label, an 125I-labeled, 4-hydroxy-3-iodophenyl
acid (DOTA) group was synthesized and
attached to the human HER2 (EGFR2; ErbB2; neu) antibody Herceptin trastuzumab. In a
mouse xenograft model of breast cancer, the labeled Herceptin had higher
retention levels than 125I tyrosine-modified Herceptin, although
comparable levels of the antibodies were detected in plasma. Next steps
include generating further derivatives of the probe and evaluating the
labeling method with additional therapeutic or diagnostic antibodies.
Roche and its Genentech Inc. unit market
Herceptin, a humanized mAb against HER2, to treat breast and gastric cancer.
Published online Dec. 5, 2013
Patent application filed;
may be available for partnerships and collaborations
Boswell, C.A. et al. J.
Med. Chem.; published online Oct. 16, 2013;
Contact: C. Andrew Boswell, Genentech Research and Early
South San Francisco, Calif.
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