Abstract:
Tumour metabolism can be imaged with a novel imaging technique termed hyperpolarised carbon-13 (13C)-MRI using probes, i.e., endogenously found molecules that are labeled with 13C. Hyperpolarisation of the 13C label increases the sensitivity to a level that allows dynamic imaging of the distribution and metabolism of the probes. Dynamic imaging of [1-13C]pyruvate metabolism is of particular biological interest in cancer because of the Warburg effect resulting in the intratumoural accumulation of [1-13C]pyruvate and conversion to [1-13C]lactate. Numerous preclinical studies in breast cancer and other tumours have shown that hyperpolarised 13C-pyruvate has potential for metabolic phenotyping and response assessment at earlier timepoints than the current clinical imaging techniques allow. The clinical feasibility of hyperpolarised 13C-MRI after the injection of pyruvate in patients with breast cancer has now been demonstrated, with increased 13C-label exchange between pyruvate and lactate present in higher grade tumours with associated increased expression of the monocarboxylate transporter 1 (MCT1), the transmembrane transporter mediating intracellular pyruvate uptake, and lactate dehydrogenase (LDH) as the enzyme catalysing the conversion of pyruvate to lactate. Furthermore, a study in patients with breast cancer undergoing neoadjuvant chemotherapy suggested that early changes in 13C-label exchange can distinguish between patients who reach pathologic complete response (pCR) and those who do not. This review summarises the current literature on preclinical and clinical research on hyperpolarised 13C-MRI with [1-13C]-pyruvate in breast cancer imaging.
摘要:
肿瘤代谢可以用一种称为超极化碳-13(13C)-MRI的新型成像技术进行成像,即,内源性发现用13C标记的分子。13C标记的超极化将灵敏度增加到允许探针的分布和代谢的动态成像的水平。[1-13C]丙酮酸代谢的动态成像在癌症中具有特别的生物学意义,因为Warburg效应导致[1-13C]丙酮酸的肿瘤内积累并转化为[1-13C]乳酸。乳腺癌和其他肿瘤的许多临床前研究表明,超极化的13C-丙酮酸盐具有在比当前临床成像技术所允许的更早时间点进行代谢表型和反应评估的潜力。现在已经证明了乳腺癌患者注射丙酮酸后超极化13C-MRI的临床可行性,与丙酮酸和乳酸之间的13C-标记交换增加存在于较高级别的肿瘤与相关的单羧酸转运蛋白1(MCT1)的表达增加,介导细胞内丙酮酸摄取的跨膜转运蛋白,和乳酸脱氢酶(LDH)作为催化丙酮酸转化为乳酸的酶。此外,一项针对接受新辅助化疗的乳腺癌患者的研究表明,13C标记物交换的早期变化可以区分达到病理完全缓解(pCR)的患者和未达到病理完全缓解的患者.这篇综述总结了关于[1-13C]-丙酮酸超极化13C-MRI在乳腺癌成像中的临床前和临床研究的最新文献。