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Hyperpolarized 13C-pyruvate MRI detects real-time metabolic flux in prostate cancer metastases to bone and liver: a clinical feasibility study.
Prostate Cancer and Prostatic Diseases ( IF 5.1 ) Pub Date : 2019-11-04 , DOI: 10.1038/s41391-019-0180-z
Hsin-Yu Chen 1 , Rahul Aggarwal 2 , Robert A Bok 1 , Michael A Ohliger 1 , Zi Zhu 1 , Philip Lee 1 , Jeremy W Gordon 1 , Mark van Criekinge 1 , Lucas Carvajal 1 , James B Slater 1 , Peder E Z Larson 1 , Eric J Small 2 , John Kurhanewicz 1 , Daniel B Vigneron 1
Affiliation  

BACKGROUND Hyperpolarized (HP) 13C-pyruvate MRI is a stable-isotope molecular imaging modality that provides real-time assessment of the rate of metabolism through glycolytic pathways in human prostate cancer. Heretofore this imaging modality has been successfully utilized in prostate cancer only in localized disease. This pilot clinical study investigated the feasibility and imaging performance of HP 13C-pyruvate MR metabolic imaging in prostate cancer patients with metastases to the bone and/or viscera. METHODS Six patients who had metastatic castration-resistant prostate cancer were recruited. Carbon-13 MR examination were conducted on a clinical 3T MRI following injection of 250 mM hyperpolarized 13C-pyruvate, where pyruvate-to-lactate conversion rate (kPL) was calculated. Paired metastatic tumor biopsy was performed with histopathological and RNA-seq analyses. RESULTS We observed a high rate of glycolytic metabolism in prostate cancer metastases, with a mean kPL value of 0.020 ± 0.006 (s-1) and 0.026 ± 0.000 (s-1) in bone (N = 4) and liver (N = 2) metastases, respectively. Overall, high kPL showed concordance with biopsy-confirmed high-grade prostate cancer including neuroendocrine differentiation in one case. Interval decrease of kPL from 0.026 at baseline to 0.015 (s-1) was observed in a liver metastasis 2 months after the initiation of taxane plus platinum chemotherapy. RNA-seq found higher levels of the lactate dehydrogenase isoform A (Ldha,15.7 ± 0.7) expression relative to the dominant isoform of pyruvate dehydrogenase (Pdha1, 12.8 ± 0.9). CONCLUSIONS HP 13C-pyruvate MRI can detect real-time glycolytic metabolism within prostate cancer metastases, and can measure changes in quantitative kPL values following treatment response at early time points. This first feasibility study supports future clinical studies of HP 13C-pyruvate MRI in the setting of advanced prostate cancer.

中文翻译:

超极化13C丙酮酸MRI可检测前列腺癌转移至骨骼和肝脏的实时代谢通量:一项临床可行性研究。

背景技术超极化(HP)13 C-丙酮酸MRI是一种稳定同位素分子成像方法,其提供通过人前列腺癌中糖酵解途径的代谢速率的实时评估。迄今为止,这种成像方式仅在局部疾病中已成功地用于前列腺癌。这项初步临床研究调查了HP 13C-丙酮酸MR代谢成像在患有骨和/或内脏转移的前列腺癌患者中的可行性和成像性能。方法招募了6例转移性去势抵抗性前列腺癌患者。在注射250 mM超极化的13C-丙酮酸盐后,在临床3T MRI上进行了Carbon-13 MR检查,并计算了丙酮酸盐至乳酸的转化率(kPL)。用组织病理学和RNA-seq分析进行配对的转移性肿瘤活检。结果我们观察到前列腺癌转移中的糖酵解代谢率很高,骨骼(N = 4)和肝脏(N = 2)的平均kPL值分别为0.020±0.006(s-1)和0.026±0.000(s-1)。 )转移。总体而言,高kPL与活检证实的高度前列腺癌(包括神经内分泌分化)一致。在紫杉烷加铂类化疗开始后2个月的肝转移中,观察到kPL从基线的0.026下降到0.015(s-1)的时间间隔。RNA-seq发现,相对于丙酮酸脱氢酶的主要同工型(Pdha1,12.8±0.9),乳酸脱氢酶同工型A(Ldha,15.7±0.7)的表达水平更高。结论HP 13C丙酮酸MRI可以检测前列腺癌转移灶内的实时糖酵解代谢,并可以在早期反应后测量定量kPL值的变化。这项第一个可行性研究支持HP 13C-丙酮酸MRI在晚期前列腺癌中的未来临床研究。
更新日期:2019-11-04
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