Non-invasive MR thermometry using a paramagnetic complex

描述（由申请人提供）：非侵入性测温是 局部热疗作为一种治疗方式的未来进展。电流 磁共振（MR）测温方法由于 1H水信号的化学位移相对较弱地依赖于 温度本研究的主要目的是开发无创MR 用于可靠和准确监测和成像的温度测量方法 使用顺磁性镧系元素络合物在肿瘤中测量温度。 我们的初步数据表明，原型镧系元素的1H化学位移 钍-1，4，7，10-四氮杂环十二烷-1，4，7，10-四乙酸盐络合物 （TmDOTA）对温度的敏感性比TmDOTA高大约两个数量级。 水，从而提供了极好的精度和分辨率。此外，本发明还提供了一种方法， TmDOTA质子位移对顺磁络合物浓度不敏感， pH、[Ca 2 +]或存在血浆大分子和离子。这将大大 简化了使用镧系配合物进行MR测温的程序 因为已知热疗会引起组织pH值和其他 参数 本项目的主要目标是：1）调查甲基 TmDOTK的取代类似物，铥1，4，7，10-四氮杂环癸烷-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MR测温技术，用于可靠、准确和快速成像， 3）以证明在体内使用TmDOTMk复合物的可行性 小鼠肿瘤热疗期间温度的监测和成像 4）对高温的急性效应进行初步研究 对肿瘤乳酸和灌注的影响TmDOTMA的主要优点是， 来自甲基的质子信号比来自甲基的质子信号更强烈和更尖锐。 来自TmDOTA的质子信号。这将大大有助于改善空间， 温度成像中时间和热分辨率。TmDOTk和TmDOTMK是 预期是无毒的，因为临床上类似的钆络合物 用作MR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.