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Clin Cancer Res. 2007 Oct 15;13(20):6070-9.

Evaluation of an 111In-radiolabeled peptide as a targeting and imaging agent for ErbB-2 receptor expressing breast carcinomas.

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Department of Biochemistry, University of Missouri-Columbia, Columbia, Missouri 65212, USA.



The cellular targeting and tumor imaging properties of a novel ErbB-2-avid peptide, discovered from bacteriophage display, were evaluated in human breast carcinoma cells and in breast carcinoma-xenografted mice.


The affinity of the ErbB-2 targeting peptide KCCYSL and its alanine substituted counterparts for the extracellular domain (ECD) of purified recombinant ErbB-2 (ErbB-2-ECD) was assessed by fluorescence titration. Binding of the KCCYSL peptide to breast and prostate carcinoma cells was analyzed by confocal microscopy. A DOTA(GSG)-KCCYSL peptide conjugate was radiolabeled with 111In, and stability, target binding, and internalization were analyzed in vitro. In vivo biodistribution and single-photon emission computed tomography imaging studies were done with the radiolabeled peptide in MDA-MB-435 human breast tumor-bearing severe combined immunodeficient mice.


KCCYSL peptide exhibited high affinity (295 +/- 56 nmol/L) to ErbB-2-ECD. Substitution of alanine for lysine, tryptophan, and cysteine reduced the peptide affinity approximately 1- to 2.4-fold, whereas replacing leucine completely abolished binding. Both biotin-KCCYSL and 111In-DOTA(GSG)-KCCYSL were capable of binding ErbB-2-expressing human breast carcinoma cells in vitro. Approximately 11% of the total bound radioactivity was internalized in the carcinoma cells. Competitive binding studies indicated that the radiolabeled peptide exhibited an IC(50) value of 42.5 +/- 2.76 nmol/L for the breast carcinoma cells. 111In-DOTA(GSG)-KCCYSL was stable in serum and exhibited rapid tumor uptake (2.12 +/- 0.32 %ID/g) at 15 min postinjection and extended retention coupled with rapid whole body disappearance, as observed by biodistribution and single-photon emission computed tomography imaging studies, respectively.


The DOTA(GSG)-KCCYSL peptide has the potential to be used as a tumor-imaging agent and a vehicle for specific delivery of radionuclide or cytotoxic agents for tumors overexpressing ErbB-2.

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