In vivo evaluation of an 111In-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. 125I-Tyr(5)-6-Ahx-Phe(19)-ST[1-19] with guanylate cyclase -C (GC-C) receptors on human colon cancer LS-180 cells revealed an IC(50) value of 7.7 +/- 0.1.6 nM. The in vitro cellular residualization studies of the 111In-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 cells in an agonistic fashion. In vivo biodistribution studies in LS-180 tumor bearing SCID mice demonstrates that the 111In-DOTA-NCS-ST peptide targets the tumor with a specific uptake of 0.94 +/- 0.31%ID/g at 1 hr p.i. and approximately 23% was retained by the tumor at 4 hrs p.i. The radioactivity cleared 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 liver and intestines, demonstrates preferential clearance of the radioactivity through the renal/urinary pathway. The specific in vitro and in vivo accumulation of the radioactivity by LS-180 human colonic cancer cells highlights the potential of radiometallated-DOTA-ST analogs as diagnostic/therapeutic radiopharmaceuticals.
Gali
H
H
Department of Radiology, University of Missouri-Columbia, Columbia, MO 65211, USA.
Sieckman
G L
GL
Hoffman
T J
TJ
Owen
N K
NK
Chin
D T
DT
Forte
L R
LR
Volkert
W A
WA
D000818:Animals; D001667:Binding, Competitive; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging*; D005260:Female; D005768:Gastrointestinal Hormones; D006573:Heterocyclic Compounds, 1-Ring / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D045265:Natriuretic Peptides; D010455:Peptides / Q000378:metabolism; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000378:metabolism / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D005768:Gastrointestinal Hormones; D006573:Heterocyclic Compounds, 1-Ring; C440168:In-DOTA-NSC-ST; D045265:Natriuretic Peptides; D010455:Peptides; D019275:Radiopharmaceuticals; C072685:guanylin