Data supporting "Analysis of 13C and 14C labeling in pyruvate and lactate in tumor and blood of lymphoma-bearing mice injected with 13C- and 14C-labeled pyruvate"

Measurements of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool can give an apparent first order rate constant for the exchange. Determination of isotope flux, however, requires an estimate of the labeled pyruvate concentration in the tumor. This was achieved here by measuring tumor uptake of [1-14C]pyruvate, which showed that <2% of the injected pyruvate reached the tumor site. Multiplication of this estimated labeled pyruvate concentration in the tumor with the apparent first order rate constant for hyperpolarized 13C label exchange gave an isotope flux that showed good agreement with a flux determined directly by injecting non polarized [3-13C]pyruvate and then rapidly excising the tumor after 30 s and measuring 13C-labeled lactate concentrations in tumor extracts. The distribution of labeled lactate between intra- and extracellular compartments and the blood pool was investigated by imaging, by measuring labeled lactate concentration in blood and tumor, and by examining the effects of a gadolinium contrast agent and a lactate transport inhibitor on the intensity of the hyperpolarized [1-13C]lactate signal. These measurements showed that there was significant export of labeled lactate from the tumor but that labeled lactate in the blood pool produced by injection of hyperpolarized [1-13C]pyruvate has only relatively low levels of polarization. This study has shown that measurements of hyperpolarized 13C label exchange between pyruvate and lactate in a murine tumor model can provide an estimate of the true isotope flux if the concentration of labeled pyruvate that reaches the tumor can be determined.

对注射型[1-13C]丙酮酸（[1-13C]pyruvate）与内源性肿瘤乳酸池之间的超极化（hyperpolarized）13C标记交换进行检测，可获得该交换过程的表观一级速率常数。然而，要测定同位素通量（isotope flux），则需对肿瘤内标记丙酮酸的浓度进行估算。本研究通过检测[1-14C]丙酮酸（[1-14C]pyruvate）的肿瘤摄取量完成了该估算，结果显示仅不足2%的注射型丙酮酸可抵达肿瘤部位。将该估算得到的肿瘤内标记丙酮酸浓度，与超极化13C标记交换的表观一级速率常数相乘，即可得到同位素通量；该通量与直接检测法所得结果吻合度良好：直接检测法通过注射非极化[3-13C]丙酮酸（[3-13C]pyruvate），于30秒后快速切除肿瘤，并检测肿瘤提取物中的13C标记乳酸浓度以完成测定。本研究通过成像技术、检测血液与肿瘤内标记乳酸浓度，以及探究钆造影剂（gadolinium contrast agent）与乳酸转运抑制剂（lactate transport inhibitor）对超极化[1-13C]乳酸（[1-13C]lactate）信号强度的影响，对标记乳酸在细胞内外间隔室与血液池中的分布情况进行了研究。上述检测结果显示，肿瘤会大量输出标记乳酸，但通过注射超极化[1-13C]丙酮酸所产生的血液池内标记乳酸，其极化水平仅相对较低。本研究证实，若可确定抵达肿瘤的标记丙酮酸浓度，那么在小鼠肿瘤模型（murine tumor model）中检测丙酮酸与乳酸之间的超极化13C标记交换，即可估算得到真实的同位素通量。