Non-invasive MR thermometry using a paramagnetic complex

描述(申请人提供)：非侵入性体温测量是 局部热疗作为一种治疗方式的未来进展。当前 磁共振(MR)测温方法由于以下原因而分辨率较低 ~1H水信号的化学位移相对较弱的依赖性 温度。本研究的主要目的是研制无创磁共振成像技术。 用于可靠和准确地监测和成像的温度测量方法 使用顺磁性稀土络合物测量肿瘤的温度。 我们的初步数据显示，一个原型镧系元素的~1H化学位移 配合物-1，4，7，10-四氮杂环十二烷-1，4，7，10-四乙酸酯 (TmDOTA)，对温度的敏感度比 因此，它可以提供极高的精度和分辨率。此外, TmDOTA质子移位对顺磁性络合物浓度不敏感， PH、[Ca~(2+)]或血浆大分子和离子的存在。这将极大地 简化使用稀土络合物进行磁共振测温的步骤 因为众所周知，高温会引起组织pH和其他组织的变化 参数。 该项目的主要目标是：1)调查甲基 TmDOTK的取代类似物1，4，7，10-四氮杂环十二烷-a，a ，a，“a”-四甲基-1，4，7，10-四乙酸酯(TmDOTMA)，用于MR测温，2)至 开发磁共振测温技术，以实现可靠、准确和快速的成像 温度使用TmDOTMk络合物，3)证明在体内的可行性 小鼠肿瘤热疗过程中的温度监测与成像 4)对高温的急性效应进行初步研究。 肿瘤乳酸盐和血流灌注。TmDOTMA的主要优势是 与来自甲基的质子信号相比，来自甲基的质子信号更强更尖锐 来自TmDOTA的质子信号。这将大大有助于改善空间， 温度成像中的时间和热分辨率。TmDOTk和TmDOTMK是 预计是无毒的，因为临床上类似的Gd络合物 用作磁共振造影剂。

DESCRIPTION (Provided by Applicant): Noninvasive thermometry is pivotal to the future advances of regional hyperthermia as a treatment modality. Current magnetic resonance (MR) thermometry methods suffer from poor resolution due to relatively weak dependence of chemical shift of the 1H water signal on temperature. The main objective of this research is to develop noninvasive MR thermometry methods for reliable and accurate monitoring and imaging of temperature in tumors using a paramagnetic lanthanide complex. Our preliminary data show that 1H chemical shifts of a prototype lanthanide complex, thulium- 1,4,7,10-tetraazacyclododecane-1 ,4,7,10- tetraacetate (TmDOTA), are about two orders of magnitudes more sensitive to temperature than the water and thus, provide excellent accuracy and resolution. In addition, TmDOTA proton shifts are insensitive to the paramagnetic complex concentration, ph, [Ca2+] or presence of plasma macromolecules and ions. This will greatly simplify the procedures for using the lanthanide complex for MR thermometry because hyperthermia is known to produce changes in tissue pH and other parameters. The main goals of this project are: 1) to investigate the use of methyl substituted analogs of TmDOTK, thulium 1,4,7,1 0-Tetraazacyclodoecane-a,a ,a,"a"-tetramethyl-1 ,4,7, 1 0-tetraacetate (TmDOTMA) for MR thermometry, 2) to develop MR thermometry techniques for reliable, accurate and rapid imaging of temperature using a TmDOTMk complex, 3) to demonstrate feasibility of in vivo monitoring and imaging of temperature during hyperthermia in a mouse tumor model, and 4) to perform a preliminary study on acute effects of hyperthermia on tumor lactate and perfusion. The major advantage of the TmDOTMA is that the proton signals from methyl groups are more intense and sharper compared to the proton signals from TmDOTA. This will greatly help in improving the spatial, temporal and thermal resolution in temperature imaging. TmDOTk and TmDOTMK are expected to be non-toxic because similar complexes of gadolinium are clinically used as MR contrast agents.