Department of Molecular and Medical Pharmacology, David Geffen UCLA School of Medicine, Los Angeles, California
Department of Molecular and Medical Pharmacology, David Geffen UCLA School of Medicine, Los Angeles, California.
J Nucl Med. 2020 Jun;61(6):931-937. doi: 10.2967/jnumed.119.237446. Epub 2019 Nov 1.
2-Deoxy-2-F-fluoro-d-glucose (2-FDG) with PET is undeniably useful in the clinic, being able, among other uses, to monitor change over time using the 2-FDG SUV metric. This report suggests some potentially serious caveats for this and related roles for 2-FDG PET. Most critical is the assumption that there is an exact proportionality between glucose metabolism and 2-FDG metabolism, called the lumped constant, or LC. This report describes that LC is not constant for a specific tissue and may be variable before and after disease treatment. The purpose of this work is not to deny the clinical value of 2-FDG PET; it is a reminder that when one extends the use of an appropriately qualified imaging method, new observations may arise and further validation would be necessary. The current understanding of glucose-based energetics in vivo is based on the quantification of glucose metabolic rates with 2-FDG PET, a method that permits the noninvasive assessment of various human disorders. However, 2-FDG is a good substrate only for facilitated-glucose transporters (GLUTs), not for sodium-dependent glucose cotransporters (SGLTs), which have recently been shown to be distributed in multiple human tissues. Thus, the GLUT-mediated in vivo glucose utilization measured by 2-FDG PET would be masked to the potentially substantial role of functional SGLTs in glucose transport and use. Therefore, under these circumstances, the 2-FDG LC used to quantify in vivo glucose utilization should not be expected to remain constant. 2-FDG LC variations have been especially significant in tumors, particularly at different stages of cancer development, affecting the accuracy of quantitative glucose measures and potentially limiting the prognostic value of 2-FDG, as well as its accuracy in monitoring treatments. SGLT-mediated glucose transport can be estimated using α-methyl-4-deoxy-4-F-fluoro-d-glucopyranoside (Me-4FDG). Using both 2-FDG and Me-4FDG should provide a more complete picture of glucose utilization via both GLUT and SGLT transporters in health and disease states. Given the widespread use of 2-FDG PET to infer glucose metabolism, it is relevant to appreciate the potential limitations of 2-FDG as a surrogate for glucose metabolic rate and the potential reasons for variability in LC. Even when the readout for the 2-FDG PET study is only an SUV parameter, variability in LC is important, particularly if it changes over the course of disease progression (e.g., an evolving tumor).
2-脱氧-2-F-氟-D-葡萄糖（2-FDG）与 PET 结合在临床上无疑是有用的，它能够通过 2-FDG SUV 指标来监测随时间的变化。本报告提出了一些与 2-FDG PET 相关的潜在严重警告。最重要的是，葡萄糖代谢与 2-FDG 代谢之间存在精确比例的假设，称为聚集常数或 LC。本报告描述了 LC 对于特定组织不是恒定的，并且在疾病治疗前后可能是可变的。本工作的目的不是否认 2-FDG PET 的临床价值；这只是提醒人们，当人们扩展使用适当合格的成像方法时，可能会出现新的观察结果，并且需要进一步验证。目前对体内葡萄糖能量代谢的理解是基于用 2-FDG PET 定量葡萄糖代谢率，该方法允许对各种人类疾病进行非侵入性评估。然而，2-FDG 只是促进型葡萄糖转运体（GLUTs）的良好底物，而不是钠依赖性葡萄糖共转运体（SGLTs）的底物，最近已经表明 SGLTs 分布在多种人类组织中。因此，通过 2-FDG PET 测量的体内 GLUT 介导的葡萄糖利用将被屏蔽掉功能性 SGLTs 在葡萄糖转运和利用中的潜在重要作用。因此，在这种情况下，用于量化体内葡萄糖利用的 2-FDG LC 不应期望保持不变。2-FDG LC 的变化在肿瘤中尤其明显，特别是在癌症发展的不同阶段，这会影响定量葡萄糖测量的准确性，并可能限制 2-FDG 的预后价值，以及其在监测治疗中的准确性。使用α-甲基-4-脱氧-4-F-氟-D-吡喃葡萄糖苷（Me-4FDG）可以估计 SGLT 介导的葡萄糖转运。使用 2-FDG 和 Me-4FDG 应该可以更全面地了解健康和疾病状态下 GLUT 和 SGLT 转运体通过葡萄糖的利用。鉴于 2-FDG PET 被广泛用于推断葡萄糖代谢，了解 2-FDG 作为葡萄糖代谢率替代物的潜在局限性以及 LC 变化的潜在原因是很重要的。即使 2-FDG PET 研究的读出结果仅是 SUV 参数，LC 的变异性也很重要，特别是如果它在疾病进展过程中发生变化（例如，正在发展的肿瘤）。
