In vitro and in vivo characterization of a new receptor specific indium‐111 labeled DOTA‐ST conjugate for targeting guanylin receptors in human colon cancer cells

A new DOTA-6-Ahx-Phe19-ST[1–19] conjugate (DOTA-Ahx-ST), for specific targeting of guanylin receptors expressed on human colon cancer cells, was synthesized and radiolabeled with indium-111. In vitro competitive binding assays, employing T-84 human colon cancer cells, demonstrated an IC50 value of 3.0 ± 0.7 nM for the In-DOTA-Ahx-ST conjugate. In vivo pharmacokinetic studies of 111In-DOTA-Ahx-ST conjugate in T-84 human colon cancer derived xenografts in SCID mice conducted at 1, 4, and 24 hrs p.i. revealed efficient clearance from the blood pool (0.31 ± 0.06 %ID/g, 1 hr p.i.) with excretion mainly through the renal pathway (92.7 ± 0.5 %ID, 1 hr p.i.). Initial tumor uptake of 1.34 ± 0.20 %ID/g at 1 hr p.i. was observed with 54% and 18% retention at 4 and 24 hrs p.i. respectively. These results suggest that this DOTA-Ahx-ST peptide conjugate or a similar analogue may have an application as a radiopharmaceutical in the detection and treatment of human colon cancer using an appropriate radioisotope.