Liu Yutong, Gauthier Gabriel C, Gendelman Howard E, Bade Aditya N
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
Department of Radiology, University of Nebraska Medical Center, Omaha, NE, USA.
NeuroImmune Pharm Ther. 2023 Mar 25;2(1):63-69. doi: 10.1515/nipt-2022-0012. Epub 2022 Sep 13.
Spatial-temporal biodistribution of antiretroviral drugs (ARVs) can now be achieved using MRI by utilizing chemical exchange saturation transfer (CEST) contrasts. However, the presence of biomolecules in tissue limits the specificity of current CEST methods. To overcome this limitation, a Lorentzian line-shape fitting algorithm was developed that simultaneously fits CEST peaks of ARV protons on its Z-spectrum.
This algorithm was tested on the common first line ARV, lamivudine (3TC), that has two peaks resulting from amino (-NH) and hydroxyl (-OH) protons in 3TC. The developed dual-peak Lorentzian function fitted these two peaks simultaneously, and used the ratio of -NH and -OH CEST contrasts as a constraint parameter to measure 3TC presence in brains of drug-treated mice. 3TC biodistribution calculated using the new algorithm was compared against actual drug levels measured using UPLC-MS/MS. In comparison to the method that employs the -NH CEST peak only, the dual-peak Lorentzian fitting algorithm showed stronger correlation with brain tissue 3TC levels, signifying estimation of actual drug levels.
We concluded that 3TC levels can be extracted from confounding CEST effects of tissue biomolecules resulting in improved specificity for drug mapping. This algorithm can be expanded to measure a variety of ARVs using CEST MRI.
利用化学交换饱和转移（CEST）对比，现在可以通过磁共振成像（MRI）实现抗逆转录病毒药物（ARV）的时空生物分布。然而，组织中生物分子的存在限制了当前CEST方法的特异性。为克服这一限制，开发了一种洛伦兹线形拟合算法，该算法可同时拟合ARV质子在其Z谱上的CEST峰。
该算法在常用的一线抗逆转录病毒药物拉米夫定（3TC）上进行了测试，3TC中的氨基（-NH）和羟基（-OH）质子产生两个峰。所开发的双峰洛伦兹函数同时拟合这两个峰，并将-NH和-OH CEST对比的比值作为约束参数来测量药物治疗小鼠大脑中3TC的存在情况。将使用新算法计算的3TC生物分布与使用超高效液相色谱-串联质谱（UPLC-MS/MS）测量的实际药物水平进行比较。与仅采用-NH CEST峰的方法相比，双峰洛伦兹拟合算法与脑组织3TC水平的相关性更强，这意味着能够估算实际药物水平。
我们得出结论，3TC水平可以从组织生物分子的混杂CEST效应中提取出来，从而提高药物图谱绘制的特异性。该算法可扩展用于通过CEST MRI测量多种抗逆转录病毒药物。
