Department of Pharmacology and Experimental Neuroscience.
Department of Radiology, University of Nebraska Medical Center, Omaha, NE, USA.
AIDS. 2021 Sep 1;35(11):1733-1741. doi: 10.1097/QAD.0000000000002960.
Antiretroviral drug theranostics facilitates the monitoring of biodistribution and efficacy of therapies designed to target HIV type-1 (HIV-1) reservoirs. To this end, we have now deployed intrinsic drug chemical exchange saturation transfer (CEST) contrasts to detect antiretroviral drugs within the central nervous system (CNS).
CEST effects for lamivudine (3TC) and emtricitabine (FTC) were measured by asymmetric magnetization transfer ratio analyses. The biodistribution of 3TC in different brain sub-regions of C57BL/6 mice treated with lipopolysaccharides was determined using MRI. CEST effects of 3TC protons were quantitated by Lorentzian fitting analysis. 3TC levels in plasma and brain regions were measured using ultraperformance liquid chromatography tandem mass spectrometry to affirm the CEST test results.
CEST effects of the hydroxyl and amino protons in 3TC and FTC linearly correlated to drug concentrations. 3TC was successfully detected in vivo in brain sub-regions by MRI. The imaging results were validated by measurements of CNS drug concentrations.
CEST contrasts can be used to detect antiretroviral drugs using MRI. Such detection can be used to assess spatial--temporal drug biodistribution. This is most notable within the CNS where drug biodistribution may be more limited with the final goal of better understanding antiretroviral drug-associated efficacy and potential toxicity.
抗逆转录病毒药物治疗诊断学有助于监测针对 HIV-1（HIV-1）储库设计的治疗方法的生物分布和疗效。为此，我们现在已经部署了内在药物化学交换饱和转移（CEST）对比来检测中枢神经系统（CNS）内的抗逆转录病毒药物。
通过不对称磁化转移比分析测量了拉米夫定（3TC）和恩曲他滨（FTC）的 CEST 效应。使用 MRI 测定用脂多糖处理的 C57BL/6 小鼠不同脑区中 3TC 的分布。通过洛伦兹拟合分析定量测定 3TC 质子的 CEST 效应。使用超高效液相色谱串联质谱法测量血浆和脑区中的 3TC 水平，以确认 CEST 测试结果。
3TC 和 FTC 中羟基和氨基质子的 CEST 效应与药物浓度呈线性相关。通过 MRI 成功地在体内检测到脑区中的 3TC。成像结果通过 CNS 药物浓度的测量得到验证。
CEST 对比可以用于使用 MRI 检测抗逆转录病毒药物。这种检测可用于评估药物的时空生物分布。在中枢神经系统中最为明显，因为药物的生物分布可能更有限，最终目的是更好地了解抗逆转录病毒药物相关的疗效和潜在毒性。
