The aim of these studies was to develop new radiometallated E. Coli STh analogs for specific in vivo targeting of guanylin/guanylate cyclase-C [GC-C] receptors that have been shown to be expressed in high densities on the surface of primary and metastatic human colon cancer cells.   STh is a 19 amino acid tri-disulfide peptide and reproducible production of the correct conformer of STh-conjugates is challenging.  Synthesis of STh-DOTA conjugates was accomplished by air-oxidation of the linear peptide and selective sequential deprotection of thiol groups, followed by susequent HPLC purification. Studies with 111In-DOTA-STh (1-19) conjugates demonstrated their high in vitro binding affinity [i.e., in 1 � 20 the nMolar range] to GC-C receptors expressed on T84 human colon cancer cells, selective uptake in T84 xenografts in SCID mice, along with rapid blood clearance and minimal liver uptake. These results indicate their potential as molecular imaging radiopharmaceuticals for colon cancer.

Design and development of radiometallated E.Coli STh conjugates for molecular imaging of human colon cancers

243rd National Meeting (2012)

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