MAGNETIC FIELD & APPLICATION FOR MR SUSCEPTIBILITY QUANTIFICATION

磁场

• 批准号: 6657644
• 负责人: LIN Z LI
• 金额: $ 22.55万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6657644
• 关键词: Mammalia; animal tissue; bioimaging /biomedical imaging; biomedical resource; carbohydrates; diabetes mellitus; human tissue; magnetic resonance imaging; neoplasm /cancer; radiology; technology /technique

We are developing a number of strategies for monitoring gene therapy. The first approach is to monitor the specific phenotype of the genetic disease. For example, in mucopolysaccharidosis type VII (MPS VII) the genetic defect is failure to produce -glucuronidase. We are synthesizing glucuronides of fluorinated phenols. When the glycosidic bond is cleaved by -glucuronidase , the 19F chemical shift of the liberated phenol is expected to change by about 10ppm; furthermore, since the liberated fragment is anionic, it is expected to be trapped in the cell. In cystic fibrosis the genetic defect is in the chloride transporter (CFTR). This is known to result in an increase in the sodium and chloride concentrations in air passage fluids. We, therefore, are developing multiple quantum 23Na methods to detect and quantitate this alteration in sodium concentration. In hypercholesteremia the genetic defect is the lack of LDL receptors. We are developing methods to label LDL mole cules with magnetite so that delivery of LDL to liver lysosomes could be detected by MRI. These examples demonstrate how magnetic resonance methods can be developed to monitor genetic defects in enzymes, ion transport and receptors. However, we recognize that development of methods to monitor phenotypes of genetic defects will required an immense amount of effort and will not be completely reliable since similar genotypes may be expressed as different phenotypes or may be expressed to different extents. A more general approach is to develop a suitable marker gene that could be attached to the transfection vector and expressed by the same promotor. An ideal marker for MRI detection would be magnetite, which increases the relaxivity of water, which is 110 M in protons. Magnetite also has about a thousandfold higher relaxivity than an equivalent amount of iron (such as if found in the iron core of ferritin). Certain bacteria have the unique ability to produce magnetite from iron. T he protein responsible for this activity has been cloned and expressed in both bacterial and mammalian cells. We are exploring the utility of this protein as a marker for gene therapy.

我们正在制定许多监测基因的策略 治疗。 第一种方法是监视特定表型 遗传疾病。 例如，在粘多糖型VII中 （MPS VII）遗传缺陷是无法产生 - 葡萄糖醛酸酶。 我们 正在合成氟化苯酚的葡萄糖醛酸苷。 什么时候 糖苷键被-19F化学偏移 - 葡萄糖醛酸酶裂解 预计解放的苯酚将变化约10ppm； 此外，由于被解放的碎片是阴离子，因此可以预期 被困在细胞中。 在囊性纤维化中，遗传缺陷为 在氯化物转运蛋白（CFTR）中。 众所周知，这会导致 空气通道中的钠和氯化物浓度增加 流体。 因此，我们正在开发多种量子23NA方法 检测和定量钠浓度的改变。 在 高胆固醇遗传缺陷是缺乏LDL受体。 我们正在开发用磁铁矿标记LDL mole Cules的方法 MRI可以检测到LDL向肝溶酶体的递送。 这些示例证明了磁共振方法如何 开发用于监测酶，离子运输和 受体。 但是，我们认识到方法的发展 监测遗传缺陷的表型将需要大量 努力并且不会完全可靠，因为类似的基因型 可以表示为不同的表型，也可以表示为 不同的范围。 一种更通用的方法是开发合适的 可以连接到转染载体的标记基因和 由同一启动子表示。 MRI检测的理想标记 将是磁铁矿，增加水的松弛性，即 质子110 m。 磁铁矿还具有大约一千倍的 放松性比等效量的铁（例如在 铁蛋白的铁核）。 某些细菌具有独特的能力 从铁产生磁铁矿。 蛋白质负责 活性已被克隆和表达在细菌和哺乳动物中 细胞。 我们正在探索该蛋白作为标记的效用 基因疗法。