Gutte Henrik, Hansen Adam E, Henriksen Sarah T, Johannesen Helle H, Ardenkjaer-Larsen Jan, Vignaud Alexandre, Hansen Anders E, Børresen Betina, Klausen Thomas L, Wittekind Anne-Mette N, Gillings Nic, Kristensen Annemarie T, Clemmensen Andreas, Højgaard Liselotte, Kjær Andreas
Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen Denmark ; Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen Denmark.
Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen Denmark.
Am J Nucl Med Mol Imaging. 2014 Dec 15;5(1):38-45. eCollection 2015.
In this paper we demonstrate, for the first time, the feasibility of a new imaging concept - combined hyperpolarized (13)C-pyruvate magnetic resonance spectroscopic imaging (MRSI) and (18)F-FDG-PET imaging. This procedure was performed in a clinical PET/MRI scanner with a canine cancer patient. We have named this concept hyper PET. Intravenous injection of the hyperpolarized (13)C-pyruvate results in an increase of (13)C-lactate, (13)C-alanine and (13)C-CO2 ((13)C-HCO3) resonance peaks relative to the tissue, disease and the metabolic state probed. Accordingly, with dynamic nuclear polarization (DNP) and use of (13)C-pyruvate it is now possible to directly study the Warburg Effect through the rate of conversion of (13)C-pyruvate to (13)C-lactate. In this study, we combined it with (18)F-FDG-PET that studies uptake of glucose in the cells. A canine cancer patient with a histology verified local recurrence of a liposarcoma on the right forepaw was imaged using a combined PET/MR clinical scanner. PET was performed as a single-bed, 10 min acquisition, 107 min post injection of 310 MBq (18)F-FDG. (13)C-chemical shift imaging (CSI) was performed just after FDG-PET and 30 s post injection of 23 mL hyperpolarized (13)C-pyruvate. Peak heights of (13)C-pyruvate and (13)C-lactate were quantified using a general linear model. Anatomic (1)H-MRI included axial and coronal T1 vibe, coronal T2-tse and axial T1-tse with fat saturation following gadolinium injection. In the tumor we found clearly increased (13)C-lactate production, which also corresponded to high (18)F-FDG uptake on PET. This is in agreement with the fact that glycolysis and production of lactate are increased in tumor cells compared to normal cells. Yet, most interestingly, also in the muscle of the forepaw of the dog high (18)F-FDG uptake was observed. This was due to activity in these muscles prior to anesthesia, which was not accompanied by a similarly high (13)C-lactate production. Accordingly, this clearly demonstrates how the Warburg Effect directly can be demonstrated by hyperpolarized (13)C-pyruvate MRSI. This was not possible with (18)F-FDG-PET imaging due to inability to discriminate between causes of increased glucose uptake. We propose that this new concept of simultaneous hyperpolarized (13)C-pyruvate MRSI and PET may be highly valuable for image-based non-invasive phenotyping of tumors. This methods may be useful for treatment planning and therapy monitoring.
在本文中,我们首次证明了一种新的成像概念的可行性——联合超极化(13)C-丙酮酸磁共振波谱成像(MRSI)和(18)F-FDG-PET成像。该程序在一台临床PET/MRI扫描仪上对一只患有癌症的犬类患者进行。我们将这一概念命名为超PET。静脉注射超极化(13)C-丙酮酸会导致相对于所探测的组织、疾病和代谢状态,(13)C-乳酸、(13)C-丙氨酸和(13)C-CO2((13)C-HCO3)共振峰增加。因此,通过动态核极化(DNP)并使用(13)C-丙酮酸,现在有可能通过(13)C-丙酮酸向(13)C-乳酸的转化速率直接研究瓦伯格效应。在本研究中,我们将其与研究细胞中葡萄糖摄取的(18)F-FDG-PET相结合。使用一台联合PET/MR临床扫描仪对一只右前爪经组织学证实为脂肪肉瘤局部复发的犬类癌症患者进行成像。PET作为单床位、10分钟采集进行,在注射310 MBq(18)F-FDG后107分钟进行。在FDG-PET之后以及注射23 mL超极化(13)C-丙酮酸后30秒进行(13)C化学位移成像(CSI)。使用通用线性模型对(13)C-丙酮酸和(13)C-乳酸的峰高进行定量。解剖学(1)H-MRI包括轴向和冠状T1振动成像、冠状T2加权快速自旋回波成像以及注射钆后带有脂肪饱和的轴向T1加权快速自旋回波成像。在肿瘤中,我们发现(13)C-乳酸生成明显增加,这也与PET上高(18)F-FDG摄取相对应。这与肿瘤细胞中糖酵解和乳酸生成相比于正常细胞增加这一事实相符。然而,最有趣的是,在犬类前爪的肌肉中也观察到了高(18)F-FDG摄取。这是由于麻醉前这些肌肉的活动所致,而这并未伴随着类似的高(13)C-乳酸生成。因此,这清楚地证明了超极化(13)C-丙酮酸MRSI如何能够直接证明瓦伯格效应。由于无法区分葡萄糖摄取增加的原因,(18)F-FDG-PET成像无法做到这一点。我们提出,这种同时进行超极化(13)C-丙酮酸MRSI和PET的新概念对于基于图像的肿瘤非侵入性表型分析可能具有很高的价值。这种方法可能对治疗规划和治疗监测有用。