Imagnia AB, Box 8225, 200 41 Malmö, Sweden.
Int J Cancer. 2010 Aug 1;127(3):729-36. doi: 10.1002/ijc.25072.
Powerful analytical tools are vital for characterizing the complex molecular changes underlying oncogenesis and cancer treatment. This is particularly true, if information is to be collected in vivo by noninvasive approaches. In the recent past, hyperpolarized (13)C magnetic resonance (MR) spectroscopy has been employed to quickly collect detailed spectral information on the chemical fate of tracer molecules in different tissues at high sensitivity. Here, we report a preclinical study showing that alpha-ketoisocaproic acid (KIC) can be used to assess molecular signatures of tumors with hyperpolarized MR spectroscopy. KIC is metabolized to leucine by the enzyme branched chain amino acid transferase (BCAT), which is found upregulated in some tumors. BCAT is a putative marker for metastasis and a target of the proto-oncogene c-myc. Very different fluxes through the BCAT-catalyzed reaction can be detected for murine lymphoma (EL4) and rat mammary adenocarcinoma (R3230AC) tumors in vivo. EL4 tumors show a more than 7-fold higher hyperpolarized (13)C leucine signal relative to the surrounding healthy tissue. In R3230AC tumor on the other hand branched chain amino acid metabolism is not enhanced relative to surrounding tissues. The distinct molecular signatures of branched chain amino acid metabolism in EL4 and R3230AC tumors correlate well with ex vivo assays of BCAT activity.
强大的分析工具对于刻画肿瘤发生和癌症治疗中复杂的分子变化至关重要。如果要通过非侵入性方法在体内收集信息，这一点尤其正确。在最近的过去，极化（13）C 磁共振（MR）光谱已被用于快速收集不同组织中示踪分子化学命运的详细光谱信息，具有高灵敏度。在这里，我们报告了一项临床前研究，表明α-酮异己酸（KIC）可用于通过极化 MR 光谱评估肿瘤的分子特征。KIC 被支链氨基酸转移酶（BCAT）代谢为亮氨酸，该酶在一些肿瘤中上调。BCAT 是转移的潜在标志物，也是原癌基因 c-myc 的靶点。在体内，对鼠淋巴瘤（EL4）和大鼠乳腺腺癌（R3230AC）肿瘤进行的非常不同的 BCAT 催化反应通量检测。EL4 肿瘤相对于周围健康组织显示出高出 7 倍以上的极化（13）C 亮氨酸信号。另一方面，与周围组织相比，R3230AC 肿瘤中的支链氨基酸代谢没有增强。EL4 和 R3230AC 肿瘤中支链氨基酸代谢的独特分子特征与 BCAT 活性的离体测定密切相关。
