In Vivo Imaging of Human Colon Cancer Xenografts in Immunodeficient Mice Using

Guanylyl cyclase C (GC-C) is a transmembrane receptor ex-pressed by human intestinal cells and primary and metastatic colorectal adenocarcinomas but not by extraintestinal tissues or tumors. The Escherichia coli heat-stable enterotoxin analog, STa (5–18), is a 14–amino acid peptide that selectively binds to the extracellular domain of GC-C with subnanomolar affinity. This study examined the utility of a radiolabeled conjugate of STa (5–18) to selectively target and image extraintestinal human colon cancer xenografts in vivo in nude mice. Methods: The STa conjugate, ethoxyethyl-mercaptoacetamidoadipoylgly-cylglycine-STa (5–18) (NC100586), was synthesized and labeled with 99mTc to produce 99mTc-NC100586. This compound was intravenously administered to nude mice bearing human colon cancer xenografts, and specific targeting was evaluated by biodistribution and gamma camera imaging. Results: In CD-