LIPOSOMAL CONTRAST AGENTS FOR MR IMAGING
LIPOSOMAL CONTRAST AGENTS FOR MR IMAGING
批准号:
3194206
负责人:
Evan charles Unger
金额:
$11.89万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1989
资助国家:
美国
项目状态:
已结题
起止时间:
1989-09-30 至 1992-08-31
关键词:
biotransformation contrast media diethylenetriaminepentaacetate drug adverse effect drug design /synthesis /production gadolinium histopathology laboratory rat liposomes liver imaging /visualization /scanning liver neoplasms magnetic resonance imaging metastasis neoplasm /cancer diagnosis surface property
中文摘要
本申请涉及脂质体造影剂的发展
用于磁共振成像(MRI)以改进肝脏的检测
和脾转移,并作为肿瘤血流灌注的标志。
当前的诊断成像技术,如闪烁照相和计算机
体层摄影术(CT)不能最佳地发现肝或脾病变,
尤其是淋巴瘤。水溶性的碘化造影剂已经被
用来提高CT对恶性肿瘤的检测,但有
与血管外血管快速平衡所带来的问题
空间和快速排泄。为了克服这个问题,脂质体加碘
针对网状内皮系统的造影剂也有
被用于CT,并导致了对恶性肿瘤的更好的检测,
然而,它们的使用受到了高毒性剂量的脂质的限制
需要提供足够的碘来提供对比度增强
CT.MRI造影剂,最引人注目的是Gd-DTPA,提供对比度
增强浓度至少比CT对比度低十倍
媒体,伴随而来的毒性,由于高剂量的脂肪应该是
减少了。此外,因为脂质体可能只存在于
通过有窗上皮的循环,可以预料到
脂质体造影剂将成为更好的肿瘤指示剂
与游离Gd-DTPA相比,Gd-DTPA可能具有更多的血管密度和灌注量
指导治疗的后果。
直径为50至400 nm的大单层囊泡将通过
不同包埋造影剂的冻融挤压工艺
包括Gd-DTPA、Gd-DOTA和磁铁矿等多种脂类
作文。囊泡将根据大小来表征,
捕集效率、在生理盐水、血清和储存中的体外稳定性,
大鼠体外舒张性和循环清除性。成像
正常大鼠和荷瘤大鼠将在造影剂前后和
大鼠肝内肿瘤的MRI图像与组织学对照
分析。生物分布和毒性测试将在适当的
脂质体系统。
英文摘要
This application addresses the development of liposomal contrast agents
for Magnetic Resonance Imaging (MRI) to improve the detection of liver
and spleen metastases and to serve as a marker of tumor perfusion.
Current diagnostic imaging techniques such as scintigraphy and computed
tomography (CT) do not optimally detect hepatic or splenic lesions,
particularly lymphoma. Water-soluble iodinated contrast agents have been
used to improve the detection of malignancy by CT, but there are
attendant problems due to rapid equilibration with the extravascular
space and rapid excretion. To overcome this problem, liposomal iodinated
contrast media, which target to the reticuloendothelial system have also
been used for CT and have resulted in improved detection of malignancy,
However, a limitation to their use had been the high toxic doses of lipid
needed to deliver sufficient iodine to provide contrast enhancement by
CT. MRI contrast agents, most noticeably Gd-DTPA, provide contrast
enhancement at concentrations at least ten-fold lower than CT contrast
media, the attendant toxicity due to high doses of lipid should be
reduced. Additionally, because liposomes may only exist from the
circulation via fenestrated epithelia, it may be expected that the
liposomal contrast agent will serve as a better indicator of tumor
vascularity and hence perfusion than free Gd-DTPA, which may have
consequences for directing therapy.
Large unilamellar vesicles of 50 to 400 nm diameter will be prepared by a
freeze-thaw extrusion procedure with various enapsulated contrast media
including Gd-DTPA, Gd-DOTA and magnetite using a variety of lipid
compositions. The vesicles will be characterized with respect to size,
trapping efficiency, in vitro stability in saline, serum and on storage,
in vitro relaxivity and clearance from circulation of rats. Imaging of
normal and tumor-bearing rats will be done pre- and post-contrast and for
rats with intrahepatic tumors, MRI images correlated with histological
analysis. Biodistribution and toxicity testing will follow on appropriate
liposomal systems.
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