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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

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111In-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid-(GSG)-ANTPCGPYTHDCPVKR

, PhD
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD
Corresponding author.

Created: .

Chemical name:111In-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid-(GSG)-ANTPCGPYTHDCPVKR
Abbreviated name:111In-DOTA(GSG)-G3-C12
Agent category:Peptide
Target category:Receptor
Method of detection:Single-photon emission computed tomography (SPECT), planar gamma imaging
Source of signal:111In
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Click on protein, nucleotide (RefSeq), and gene for more information about galectin-3.



Extracellular matrix (ECM) adhesion molecules consist of a complex network of fibronectins, collagens, chondroitins, laminins, glycoproteins, heparin sulfate, tenascins, and proteoglycans that surround connective tissue cells, and they are mainly secreted by fibroblasts, chondroblasts, and osteoblasts (1). Cell substrate adhesion molecules are considered essential regulators of cell migration, differentiation, and tissue integrity and remodeling. These molecules play a role in inflammation and atherogenesis, but they also participate in the process of invasion and metastasis of malignant cells in the host tissue (2). Invasive tumor cells adhere to the ECM, which provides a matrix environment for permeation of tumor cells through the basal lamina and underlying interstitial stroma of the connective tissue. Overexpression of matrix metalloproteinases (MMPs) and other proteases by tumor cells allows intravasation of tumor cells into the circulatory system after degrading the basement membrane and ECM (3).

Galectin-3 (Gal-3) is a carbohydrate-binding protein (30 kDa) with a highly conserved carbohydrate recognition domain (CRD) at the C-terminus (4). Gal-3 is found not only on the cell surface but also in the cytoplasm and nucleus. It is also secreted into the extracellular space. Gal-3 is involved in multiple biological conditions such as cellular adhesion, apoptosis, differentiation, metastasis, and inflammation. Gal-3 is found to be overexpressed in various human cancer cells with even higher expression in metastatic cancer cells (5, 6). Interactions of Gal-3 with certain carbohydrates and ECM proteins promote tumor cell adhesion and metastasis through inhibition of tumor cell apoptosis and induction of endothelial cell proliferation and angiogenesis (7-11). The peptide ANTPCGPYTHDCPVKR (G3-C12) was identified to be a selective binder to Gal-3 with phage display screening, and G3-C12 inhibits adhesion of tumor cells to endothelial cells (12). Kumar et al. (13) introduced the linker GSG to the N-terminus alanine (A) of the G3-C12 peptide for conjugation with tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid (DOTA) for labeling with 111In. 111In-DOTA(GSG)-G3-C12 has been evaluated as a single-photon emission computed tomography (SPECT) agent for Gal-3 expression in tumors in vivo (13, 14).



DOTA-(GSG)-G3-C12 was prepared with solid-phase peptide synthesis (13). DOTA-(GSG)-G3-C12 was purified with reverse-phase high-performance liquid chromatography. Radiolabeling was performed by mixing 111InCl3 in ammonium acetate with DOTA-(GSG)-G3-C12. The mixture was heated at 85°C for 30 min. The radiochemical purity and specific activity of 111In-DOTA-(GSG)-G3-C12 were >98% and 68.5 GBq/µmol (1.9 Ci/µmol), respectively. The labeling yield was 30%. 111In-DOTA-(GSG)-G3-C12 was stable in saline for 12 h and mouse serum for 30 min with some degradation at the later time points.

In Vitro Studies: Testing in Cells and Tissues


An in vitro receptor-binding assay of 111In-DOTA-(GSG)-G3-C12 was performed on Gal-3–expressing human MDA-MB-435 breast cancer cell line (13). Binding of 111In-DOTA-(GSG)-G3-C12 to Gal-3 was ~5% of the incubation dose after 60 min of incubation at 37°C, whereas the control 111In-DOTA-(GSG)-G3-C12 scrambled peptide showed no appreciable binding. 111In-DOTA-(GSG)-G3-C12 was not internalized into the cells. In-DOTA-(GSG)-G3-C12 exhibited a 50% inhibition concentration (IC50) of 200.0 ± 6.7 nM. Deutscher et al. (14) reported that In-DOTA-(GSG)-G3-C12 inhibited 111In-DOTA-(GSG)-G3-C12 binding to human PC3-M prostate carcinoma cells with an IC50 value of 191 ± 10.2 nM.

Animal Studies



Kumar et al. (13) performed ex vivo biodistribution studies of 111In-DOTA-(GSG)-G3-C12 in nude mice (n = 3/group) bearing a human MDA-MB-435 breast tumor. Each mouse received 0.11 MBq (3 nCi) 111In-DOTA-(GSG)-G3-C12 by intravenous injection. The tumor radioactivity levels were 1.02 ± 0.75% injected dose per gram (ID/g) at 30 min, 0.75 ± 0.05% ID/g at 1 h, 0.60 ± 0.04% ID/g at 2 h, and 0.16 ± 0.04% ID/g at 4 h. The accumulation in the tumor was inhibited by 48% with pretreatment of excess non-labeled In-DOTA-(GSG)-G3-C12 (P < 0.01) at 2 h after tracer injection. The accumulation of the tracer was the highest in the kidney (25.9% ID/g), followed by the intestine (0.52% ID/g), lung (0.49% ID/g), blood (0.31% ID/g), and liver (0.25% ID/g) at 1 h after injection. The urine contained 88.6% ID at 1 h after injection. The peak tumor/blood and tumor/muscle ratios were 8.6 and 30.0 at 2 h, respectively. Whole-body SPECT imaging was performed at 2 h after 111In-DOTA-(GSG)-G3-C12 injection. The tumor and kidneys were the only tissue/organ clearly visualized. On the other hand, only the kidneys were visualized with the injection of 111In-DOTA-(GSG)-G3-C12 scrambled peptide. Deutscher et al. (14) showed similar ex vivo biodistribution and SPECT imaging results with human PC3-M prostate tumor-bearing SCID mice.

Other Non-Primate Mammals


No publication is currently available.

Non-Human Primates


No publication is currently available.

Human Studies


No publication is currently available.

NIH Support

P50 CA103130-01


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Zou J., Glinsky V.V., Landon L.A., Matthews L., Deutscher S.L. Peptides specific to the galectin-3 carbohydrate recognition domain inhibit metastasis-associated cancer cell adhesion. Carcinogenesis. 2005;26(2):309–18. [PubMed: 15528216]
Kumar S.R., Deutscher S.L. 111In-labeled galectin-3-targeting peptide as a SPECT agent for imaging breast tumors. J Nucl Med. 2008;49(5):796–803. [PubMed: 18413389]
Deutscher S.L., Figueroa S.D., Kumar S.R. Tumor targeting and SPECT imaging properties of an (111)In-labeled galectin-3 binding peptide in prostate carcinoma. Nucl Med Biol. 2009;36(2):137–46. [PubMed: 19217525]


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