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• Overseas Papers •
Evaluation of CLT1-(Gd-DTPA) for MR molecular imaging in a mouse breast cancer model
Ye Furong  Jeong Eun-Kee  Parker Denis  Lu Zheng-Rong 

DOI:10.3969/j.issn.1674-8034.2011.05.002.


[Abstract] A peptide targeted contrast agent, CLT1- (Gd-DTPA), was investigated for molecular imaging of fibrin-fribronectin complexes in tumor stroma with magnetic resonance imaging (MRI). The contrast agent was evaluated in female nude mice bearing MDA-MB-231 human breast carcinoma xenografts on a Siemens 3T clinical scanner with a clinical agent Gd (DTPA-BMA) as a non-targeted control. CLT1- (Gd-DTPA) specifically bound to tumor tissue and resulted in significant tumor contrast enhancement at a dose of 0.05 mmol/kg for at least 60 minutes after injection. In contrast, a non-targeted contrast agent, Gd(DTPA-BMA), cleared rapidly from the body with little tumor enhancement after 30 minutes post-injection at a dose of 0.1 mmol/kg. CLT1- (Gd-DTPA) had little non-specific binding in blood and normal tissues, including the liver and muscle, resulting in comparable non-specific enhancement in normal tissues to the control agent. The study has shown that CLT1-(Gd-DTPA) can bind to the tumor tissue, resulting in significant tumor enhancement in a mouse breast cancer model. The targeted contrast agent has a potential for MR molecular imaging of breast cancer.
[Keywords] Magnetic resonance imaging；Molecular imaging；Targeted contrast agent；Mouse；Breast cancer

Ye Furong Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, USA

Jeong Eun-Kee Department of Radiology, University of Utah, Salt Lake City, Utah, USA

Parker Denis Department of Radiology, University of Utah, Salt Lake City, Utah, USA

Lu Zheng-Rong* Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA

*Correspondence to: Dr. Zheng-Rong Lu, E-mail: zxl125@case.edu

Conflicts of interest   None.

Received  2011-07-11
Accepted  2011-08-19
DOI: 10.3969/j.issn.1674-8034.2011.05.002
DOI:10.3969/j.issn.1674-8034.2011.05.002.

[1]
Stephen RM, Gillies RJ. Promise and progress for functional and molecular imaging of response to targeted therapies. Pharm Res, 2007, 24(6): 1172-1185.
[2]
Caravan P, Ellison JJ, McMurry TJ, et al. Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications. Chem Rev, 1999, 99(9): 2293-2352.
[3]
Göhr-Rosenthal S, Schmitt-Willich H, Ebert W, et al. The demonstration of human tumors on nude mice using gadolinium-labelled monoclonal antibodies for magnetic resonance imaging. Invest Radiol, 1993, 28(9): 789-795.
[4]
Sipkins DA, Cheresh DA, Kazemi MR, et al. Detection of tumor angiogenesis in vivo by alphaVbeta3-targeted magnetic resonance imaging. Nat Med, 1998, 4(5): 623-626.
[5]
Curtet C, Maton F, Havet T, et al. Polylysine-Gd-DTPAn and polylysine-Gd-DOTAn coupled to anti-CEA F(ab')2 fragments as potential immunocontrast agents. Relaxometry, biodistribution, and magnetic resonance imaging in nude mice grafted with human colorectal carcinoma. Invest Radiol, 1998, 33(10):752-761.
[6]
Ke T, Jeong EK, Wang X, et al. RGD targeted poly(L-glutamic acid)-cystamine-(Gd-DO3A) conjugate for detecting angiogenesis biomarker alpha(v) beta3 integrin with MRT, mapping. Int J Nanomedicine, 2007, 2(2):191-199.
[7]
Flacke S, Fischer S, Scott MJ, et al. Novel MRI contrast agent for molecular imaging of fibrin: implications for detecting vulnerable plaques. Circulation, 2001, 104(11): 1280-1285.
[8]
Amirbekian V, Lipinski MJ, Briley-Saebo KC, et al. Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI. Proc Natl Acad Sci U S A, 2007, 104(3):961-966.
[9]
Ersoy H, Rybicki FJ. Biochemical safety profiles of gadolinium-based extracellular contrast agents and nephrogenic systemic fibrosis. J Magn Reson Imaging, 2007, 26(5): 1190-1197.
[10]
Sieber MA, Pietsch H, Walter J, et al. A preclinical study to investigate the development of nephrogenic systemic fibrosis: a possible role for gadolinium-based contrast media. Nvest Radiol, 2008, 43(1): 65-75.
[11]
Ye F, Wu X, Jeong EK, Jia Z, et al. A peptide targeted contrast agent specific to fibrin-fibronectin complexes for cancer molecular imaging with MRI. Bioconjug Chem, 2008n19(12):2300-2343.
[12]
Tan M, Wu X, Jeong EK, et al. Peptide-targeted Nanoglobular Gd-DOTA monoamide conjugates for magnetic resonance cancer molecular imaging. Biomacromolecules, 2010, 11(3):754-761.
[13]
Tan M, Wu X, Jeong EK, et al. An effective targeted nanoglobular manganese(II) chelate conjugate for magnetic resonance molecular imaging of tumor extracellular matrix. Mol Pharm, 2010, 7(4): 936-943.
[14]
Dvorak HF, Senger DR, Dvorak AM, et al. Regulation of extravascular coagulation by microvascular permeability. Science, 1985, 227(4690): 1059-1061.
[15]
Neri D, Carnemolla B, Nissim A, et al. Targeting by affinity-matured recombinant antibody fragments of an angiogenesis associated fibronectin isoform. Nat Biotechnol, 1997, 15(12): 1271-1275.
[16]
Pilch J, Brown DM, Komatsu M, et al. Peptides selected for binding to clotted plasma accumulate in tumor stroma and wounds. Proc Natl Acad Sci U S A, 2006, 103(8): 2800-2804.
[17]
Zong Y, Guo J, Ke T, et al. Effect of size and charge on pharmacokinetics and in vivo MRI contrast enhancement of biodegradable polydisulfide Gd(III) complexes. J Control Release, 2006, 112(3): 350-356.

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