Academic Unit of Radiology, Department of Infection, Immunity and Cardiovascular Disease, The Medical School, University of Sheffield, Sheffield, UK.
Department of Oncology and Metabolism, The Medical School, University of Sheffield, Sheffield, UK.
NMR Biomed. 2022 May;35(5):e4650. doi: 10.1002/nbm.4650. Epub 2021 Nov 28.
Dissolution dynamic nuclear polarisation (dDNP) of C-labelled pyruvate in magnetic resonance spectroscopy/imaging (MRS/MRSI) has the potential for monitoring tumour progression and treatment response. Pyruvate delivery, its metabolism to lactate and efflux were investigated in rat P22 sarcomas following simultaneous intravenous administration of hyperpolarised C-labelled pyruvate ( C -pyruvate) and urea ( C-urea), a nonmetabolised marker. A general mathematical model of pyruvate-lactate exchange, incorporating an arterial input function (AIF), enabled the losses of pyruvate and lactate from tumour to be estimated, in addition to the clearance rate of pyruvate signal from blood into tumour, K , and the forward and reverse fractional rate constants for pyruvate-lactate signal exchange, k and k . An analogous model was developed for urea, enabling estimation of urea tumour losses and the blood clearance parameter, K . A spectral fitting procedure to blood time-course data proved superior to assuming a gamma-variate form for the AIFs. Mean arterial blood pressure marginally correlated with clearance rates. K equalled K , indicating equivalent permeability of the tumour vasculature to urea and pyruvate. Fractional loss rate constants due to effluxes of pyruvate, lactate and urea from tumour tissue into blood (k , k and k , respectively) indicated that T s and the average flip angle, θ, obtained from arterial blood were poor surrogates for these parameters in tumour tissue. A precursor-product model, using the tumour pyruvate signal time-course as the input for the corresponding lactate signal time-course, was modified to account for the observed delay between them. The corresponding fractional rate constant, k , most likely reflected heterogeneous tumour microcirculation. Loss parameters, estimated from this model with different TRs, provided a lower limit on the estimates of tumour T for lactate and urea. The results do not support use of hyperpolarised urea for providing information on the tumour microcirculation over and above what can be obtained from pyruvate alone. The results also highlight the need for rigorous processes controlling signal quantitation, if absolute estimations of biological parameters are required.
在磁共振波谱/成像（MRS/MRSI）中，¹³C 标记的丙酮酸的溶解动态核极化（dDNP）有可能监测肿瘤的进展和治疗反应。在同时静脉内给予超极化的¹³C 标记的丙酮酸（¹³C-丙酮酸）和尿素（¹³C-尿素）后，研究了大鼠 P22 肉瘤中的丙酮酸输送、代谢为乳酸盐和流出。一个包含动脉输入函数（AIF）的丙酮酸-乳酸交换的通用数学模型，除了从血液到肿瘤的丙酮酸信号清除率 K 以及丙酮酸-乳酸信号交换的正向和反向分数速率常数 k 和 k 之外，还能够估计肿瘤中丙酮酸和乳酸盐的损失。为尿素开发了类似的模型，能够估计尿素肿瘤损失和血液清除参数 K。对血液时间过程数据的光谱拟合程序证明优于假设 AIF 的伽马变量形式。平均动脉血压与清除率略有相关性。K 等于 K ，表明肿瘤血管对尿素和丙酮酸具有同等的通透性。由于丙酮酸、乳酸盐和尿素从肿瘤组织流出到血液中的流出率常数（分别为 k、k 和 k）表明，T s 和从动脉血液获得的平均翻转角θ是肿瘤组织中这些参数的不良替代物。使用肿瘤丙酮酸信号时间过程作为相应的乳酸盐信号时间过程的输入的前体-产物模型，进行了修改以考虑到它们之间的观察到的延迟。相应的分数速率常数 k 很可能反映了肿瘤微循环的异质性。使用不同的 TR 从该模型估计的损失参数为乳酸盐和尿素提供了肿瘤 T 的下限估计值。结果不支持使用超极化的尿素来提供肿瘤微循环的信息，而不是单独从丙酮酸获得的信息。结果还强调了如果需要对生物参数进行绝对估计，则需要严格控制信号定量的过程。
