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

Abstract

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 (111)In. The in vitro cell binding properties of (111)In-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 (111)In-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 (111)In-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.

• Authors: Susan L Deutscher, Said D Figueroa, Senthil R Kumar
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 36 Issue 2 Pg. 137-46 (Feb 2009) ISSN: 0969-8051 [Print] United States
• PMID: 19217525 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antigens, Neoplasm
• Biomarkers, Tumor
• Carrier Proteins
• Galectin 3
• Glycoproteins
• Indium Radioisotopes
• LGALS3BP protein, human
• Radiopharmaceuticals

Topics

• Amino Acid Sequence
• Animals
• Antigens, Neoplasm
• Binding, Competitive
• Biomarkers, Tumor
• Carrier Proteins (metabolism)
• Cell Line, Tumor
• Female
• Galectin 3 (analysis)
• Glycoproteins (metabolism)
• Humans
• Indium Radioisotopes
• Isotope Labeling
• Male
• Mice
• Mice, SCID
• Molecular Sequence Data
• Prostatic Neoplasms (diagnostic imaging)
• Radiopharmaceuticals (pharmacokinetics)
• Tissue Distribution
• Tomography, Emission-Computed, Single-Photon (methods)