In vivo evaluation of an In-111-labeled ST-peptide analog for specific-targeting of human colon cancers

In vitro competitive binding studies of In-DOTA-NCS-6-Ahx-Phe(19)-ST[1-19] vs. I-125-Tyr(5)-6-Ahx-Phe(19)-ST[1-19] with guanylate cyclase -C (GC-C) re ceptors on human colon cancer LS-180 cells revealed an IC50 value of 7.7 +/ -0.1.6 nM. The in vitro cellular residualization studies of the In-111-DOTA -NCS-ST peptide and GC-C receptor mediated stimulated cGMP production with LS-180 cells demonstrates that this peptide selectively binds to LS-180 cel ls in an agonistic fashion. In vivo biodistribution studies in LS-180 tumor bearing SCID mice demonstrates that the In-111-DOTA-NCS-ST peptide targets the tumor with a specific uptake of 0.94 +/-0.31%ID/g at 1 hr p.i. and app roximately 23% was retained by the tumor at 4 hrs p.i. The radioactivity cl eared rapidly from the blood stream with 84.5 +/-3.4%ID at 1h p.i. found in the urine. High activity in urine and kidney, and minimal activity in live r and intestines, demonstrates preferential clearance of the radioactivity through the renal/urinary pathway. The specific in vitro and in vivo accumu lation of the radioactivity by LS-180 human colonic cancer cells highlights the potential of radiometallated-DOTA-ST analogs as diagnostic/therapeutic radiopharmaceuticals. (C) 2001 Elsevier Science Inc. All rights reserved.