Department of Radiology, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem 9112001, Israel.
Sensors (Basel). 2019 May 5;19(9):2089. doi: 10.3390/s19092089.
[1-C]pyruvate, the most widely used compound in dissolution-dynamic nuclear polarization (dDNP) magnetic resonance (MR), enables the visualization of lactate dehydrogenase (LDH) activity. This activity had been demonstrated in a wide variety of cancer models, ranging from cultured cells, to xenograft models, to human tumors in situ. Here we quantified the LDH activity in precision cut tumor slices (PCTS) of breast cancer xenografts. The Michigan Cancer Foundation-7 (MCF7) cell-line was chosen as a model for the luminal breast cancer type which is hormone responsive and is highly prevalent. The LDH activity, which was manifested as [1-C]lactate production in the tumor slices, ranged between 3.8 and 6.1 nmole/nmole adenosine tri-phosphate (ATP) in 1 min (average 4.6 ± 1.0) on three different experimental set-ups consisting of arrested vs. continuous perfusion and non-selective and selective RF pulsation schemes and combinations thereof. This rate was converted to an expected LDH activity in a mass ranging between 3.3 and 5.2 µmole/g in 1 min, using the ATP level of these tumors. This indicated the likely utility of this approach in clinical dDNP of the human breast and may be useful as guidance for treatment response assessment in a large number of tumor types and therapies ex vivo.
[1-C]丙酮酸是溶解动力学核极化（dDNP）磁共振（MR）中最广泛使用的化合物，能够可视化乳酸脱氢酶（LDH）活性。这种活性已经在各种癌症模型中得到了证明，包括培养细胞、异种移植模型以及原位人类肿瘤。在这里，我们定量测定了乳腺癌异种移植的精确切割肿瘤切片（PCTS）中的 LDH 活性。密歇根癌症基金会-7（MCF7）细胞系被选为腔型乳腺癌的模型，这种乳腺癌对激素有反应，且非常普遍。LDH 活性表现为肿瘤切片中[1-C]乳酸的产生，在三种不同的实验设置（包括停流和连续灌注、非选择性和选择性 RF 脉冲方案及其组合）中，在 1 分钟内，每毫摩尔三磷酸腺苷（ATP）的 LDH 活性范围在 3.8 到 6.1nmole 之间（平均 4.6±1.0）。使用这些肿瘤的 ATP 水平，将该速率转换为 1 分钟内质量范围在 3.3 到 5.2µmole/g 的预期 LDH 活性。这表明该方法在人体乳腺的临床 dDNP 中可能具有实用性，并且可能作为指导，用于大量肿瘤类型和治疗方法的离体治疗反应评估。
