Tumor targeting and SPECT imaging properties of an 111In-labeled galectin-3 binding peptide in prostate carcinoma

Introduction: Galectin-3 (gal-3) is a carbohydrate binding protein that has been implicated in cell adhesion. tumor invasion and metastasis. The objective of this study was to evaluate the tumor targeting and imaging properties of a gal-3 binding peptide selected by phage display in a mouse model of metastatic human prostate carcinoma expressing gal-3. Methods: A gal-3 binding peptide, ANTPCGPYTHDCPVKR, was synthesized with a Gly-Ser-Gly (GSG) spacer and 1,4,7,10-tetraazacyclododecane-N,N',N '',N '''- -tetraacetic acid (DOTA) and then radiolabeled with In-111. The in vitro cell binding properties of In-111-DOTA-(GSG)-ANTPCGPYTHDCPVKR were determined in metastatic human PC3-M prostate carcinoma cells. The pharmacokinetics and single-photon emission computed tomographic (SPECT/CT) imaging with the radiolabeled peptide were evaluated in SCID mice bearing human PC3-M prostate carcinoma tumor xenografts. Results: The radiolabeled peptide bound with a 50% inhibitory concentration of 191 +/- 10.2 nM to cultured PC3-M prostate carcinoma cells. In vivo tumor uptake and retention coupled with fast whole-body clearance of the peptide were demonstrated in PC3-M tumor-bearing SCID mice. The tumor uptake rates of the radiolabeled peptide were 1.27 +/- 0.10%ID/g at 30 min, 0.82 +/- 0.15%ID/g at 1 h and 0.57 +/- 0.09%ID/g at 2 h. MicroSPECT/CT studies revealed good tumor uptake of In-111-DOTA-(GSG)-ANTPCGPYTHDCPVKR 2 h postinjection, while uptake in normal organs was low, with the exception of the kidneys. Conclusions: In vitro cell binding along with tumor uptake of In-111-DOTA-(GSG)-ANTPCGPYTHDCPVKR in PC3-M human prostate carcinoma tumor-bearing SCID mice suggests the potential of this peptide as a radiopharmaceutical for imaging of gal-3-expressing prostate tumors. (c) 2009 Elsevier Inc. All rights reserved.