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Specific Targeting of Folate-labeled MRI Contrast Agents to the High Affinity Folate Receptor Expressed in Pulmonary Tumor Xenografts

Author: YuanZheng
Tutor: XiaoXiangSheng
School: Second Military Medical University
Course: Medical Imaging and Nuclear Medicine
Keywords: Folate receptor Magnetic resonance imaging Targeting Gd-DTPA Lung tumors
CLC: R734.2
Type: Master's thesis
Year: 2005
Downloads: 187
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Abstract

Background magnetic resonance targeted contrast agent can not only improve the diagnostic accuracy of lesion, also reflect some biological characteristics of the lesions, evaluation of treatment efficacy, clinical application of broad prospects, has become molecular imaging research focus. Tumor molecular biology studies have shown that there are a series of receptors at the surface of tumor cells or tumor-associated blood vessels surface and is overexpressed in tumor tissue, it can specifically bind to the corresponding ligand or ligand analogs. Receptor and its ligand binding specificity, selectivity, saturability, affinity, and biological effects obvious characteristics. This provides a new targeted way for tumor targeted diagnosis. Studies have shown that folate receptor (folate receptor, FR) in the majority of malignant tumors, such as ovarian cancer, endometrial cancer, lung cancer, kidney cancer, breast cancer, colon cancer and nasopharyngeal cancer is highly expressed, sometimes comparable to normal tissue is 20-300 times higher than in normal tissues, but the expression is highly conserved. Ligand folate and folic acid receptor with high affinity. The aim of the present study aims to develop targeting tumor cells via folate receptor-mediated MR folate targeting developing contrast agents Gd-DTPA-Poly-L-Lysine (folic acid-PL-Gd-DTPA) of magnetic resonance Targeting the the contrast agent folate-PL-Gd-DTPA target bearing human lung cancer in nude mice imaging feasibility and development characteristics. Materials and methods of magnetic resonance Preparation and in vitro characterization of the targeted contrast agent under alkaline conditions, the use of DTPA-modified poly-L-lysine (Poly-L-Lysine, PL) PL-DTPA synthetic macromolecules as carrier, with GdCl ₃ reaction of PL-Gd-DTPA, a synthetic macromolecular contrast agent under alkaline conditions, folate and PL-Gd-DTPA-conjugated NCKU molecular polymer, i.e. Experimental desired targeted contrast agent; using high performance liquid chromatography (HPLC) Determination of macromolecular purity, high-frequency inductively coupled plasma emission spectrometry (ICP-AES) Determination of Gd ^{by 3 content, use cell folate receptor competition binding assay prove macromolecular activity. Magnetic resonance targeted targeted contrast agents (folate-PL-Gd-DTPA) MRI studies in nude mice bearing human lung cancer H460 human lung cancer cell lines were passaged in BALB / C nude mice made nude mouse model of human lung adenocarcinoma. Injected via the tail vein Magnetic Resonance targeted contrast agent folate-PL-Gd-DTPA (n = 3), the observation model injection before and at different time points after injection of the tumor, liver and leg muscle T-_{1 WI signal value changes. 10 were randomly divided into experimental group targeted three magnetic resonance contrast agents (folate-PL-Gd-DTPA) with conventional contrast agent (Gd-DTPA) bearing human lung cancer in nude MRI imaging results in control the research bearing human lung adenocarcinoma in nude mice model The experimental animals were injected via the tail vein (n = 6) and control group (n = 4), targeted contrast agent folate-PL-Gd-DTPA and the control group were injected}}

Specific Targeting of Folate-labeled MRI Contrast Agents to the High Affinity Folate Receptor Expressed in Pulmonary Tumor Xenografts

Abstract

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