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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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Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

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111In-Diethylenetriaminepentaacetic acid-cyclo(CTTHWGFTLC)

111In-DTPA-CTT
, PhD
National for Biotechnology Information, NLM, NIH, Bethesda, MD
Corresponding author.

Created: ; Last Update: April 25, 2012.

Chemical name:111In-Diethylenetriaminepentaacetic acid- cyclo(CTTHWGFTLC)
Abbreviated name:111In-DTPA-CTT
Synonym:
Agent category:Peptide
Target:Gelatinases (MMP-2 and MMP-9)
Target category:Enzyme
Method of detection:Single-photon emission computed tomography (SPECT), gamma planar imaging
Source of signal:111In
Activation:No
Studies:
  • Checkbox In vitro
  • Checkbox Rodents
Structure is not available in PubChem.

Background

[PubMed]

Extracellular matrix (ECM) adhesion molecules consist of a complex network of fibronectins, collagens, chondroitins, laminins, glycoproteins, heparin sulfate, tenascins, and proteoglycans surrounding 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, 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 components, which provide a matrix environment for their permeation through the basal lamina and underlying interstitial stroma of the connective tissue by matrix metalloproteinases (MMPs), which degrade the basement membrane and ECM (3).

Gelatinase family is a subgroup of MMPs consisting of gelatinase A (MMP-2) and B (MMP-9) (4). Gelatinase expression in normal cells, such as trophoblasts, osteoclasts, neutrophils and macrophages, is highly regulated. Elevated level of gelatinases has been found in tumors associated with a poor prognosis in cancer patients (5). A cyclic decapeptide, cCTTHWGFTLC (CTT), was found to be a potent and selective inhibitor of MMP-2 and MMP-9 (6). The HWGF motif is important for the inhibitory activity. Diethylenetriaminepentaacetic acid was conjugated to an amino group of the N-terminal cysteine of the CTT peptide for radiolabeling with 111In. 111In-DTPA-CTT is being developed for single-photon emission computed tomography (SPECT) imaging of gelatinase activity in metastatic tumors.

Synthesis

[PubMed]

A mixture of 3.7-7.4 MBq (0.1-0.2 mCi) 111InCl3 and DTPA-CTT (10 μg) was incubated in 0.1 M acetic acid for 30 min at room temperature (7). 111In-DTPA-CTT was purified by high-performance liquid chromatography to have a radiochemical purity of >95%. The specific activity was >400 MBq/µmol (10.8 mCi/µmol).

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

Hanaoka et al. (7) reported that In-DTPA-CTT inhibited the proteolytic activity of MMP-2 with an IC50 value of 1026 μM, whereas CTT had an IC50 value of 283 μM. 111In-DTPA-CTT was ~85% intact in murine serum for 3 h at 37°C.

Animal Studies

Rodents

[PubMed]

Hanaoka et al. (7) performed biodistribution studies in nude mice (n = 4-5) bearing human breast carcinoma MDA-MB-231 (high gelatinase expression) or MDA-MB-435S (low gelatinase expression) xenografts. 111In-DTPA-CTT cleared rapidly from the blood with 0.09 ± 0.01% injected dose (ID)/g for the MDA-MB-231 and 0.16 ± 0.04% ID/g for the MDA-MB-435S tumors at 3 h. The tumor/blood ratio was 2.81 and 0.94 at 3 h, respectively. Accumulation of radioactivity was low in the liver (0.12-0.23% ID/g) and muscle (<0.01% ID/g). The majority of the radioactivity was excreted via the kidneys (7.8-9.19% ID/g at 3 h) into urine. There is a significant correlation (r = 0.801) between tumor accumulation and gelatinase activity. No blocking experiment was performed.

Other Non-Primate Mammals

[PubMed]

No publication is currently available.

Non-Human Primates

[PubMed]

No publication is currently available.

Human Studies

[PubMed]

No publication is currently available.

References

1.
Bosman F.T., Stamenkovic I. Functional structure and composition of the extracellular matrix. J Pathol. 2003;200(4):423–8. [PubMed: 12845610]
2.
Jiang W.G., Puntis M.C., Hallett M.B. Molecular and cellular basis of cancer invasion and metastasis: implications for treatment. Br J Surg. 1994;81(11):1576–90. [PubMed: 7827878]
3.
Albelda S.M. Role of integrins and other cell adhesion molecules in tumor progression and metastasis. Lab Invest. 1993;68(1):4–17. [PubMed: 8423675]
4.
Nelson A.R., Fingleton B., Rothenberg M.L., Matrisian L.M. Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol. 2000;18(5):1135–49. [PubMed: 10694567]
5.
Deryugina E.I., Quigley J.P. Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev. 2006;25(1):9–34. [PubMed: 16680569]
6.
Koivunen E., Arap W., Valtanen H., Rainisalo A., Medina O.P., Heikkila P., Kantor C., Gahmberg C.G., Salo T., Konttinen Y.T., Sorsa T., Ruoslahti E., Pasqualini R. Tumor targeting with a selective gelatinase inhibitor. Nat Biotechnol. 1999;17(8):768–74. [PubMed: 10429241]
7.
Hanaoka H., Mukai T., Habashita S., Asano D., Ogawa K., Kuroda Y., Akizawa H., Iida Y., Endo K., Saga T., Saji H. Chemical design of a radiolabeled gelatinase inhibitor peptide for the imaging of gelatinase activity in tumors. Nucl Med Biol. 2007;34(5):503–10. [PubMed: 17591550]

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