Novel Small Molecule Probes for Metastatic Melanoma

Actively targeting probe <b>1b</b>, an unsymmetrical bivalent dipeptide mimic, selectively bound melanoma over healthy skin tissue in histological samples from patients and Sinclair swine. Modifications to <b>1b</b> gave agents <b>2</b>–<b>4</b> that contain a near-IR aza-BODIPY fluor. Contrary to our expectations, symmetrical probe <b>3</b> gave the highest melanoma-to-healthy skin selectivity in histochemistry and experiments with live cells; this was surprising because <b>2</b>, not <b>3</b>, is unsymmetrical like the original lead <b>1</b>. Optical imaging of <b>3</b> in a mouse melanoma model failed to show tumor accumulation <i>in vivo</i>, but the probe did selectively accumulate in the tumor (some in lung and less in the liver) as proven by analysis of the organs post mortem